Main : Emerging Hepatitis C Treatments/Therapies Archives

May 08, 2009

Hep C Trial Shows Best Chance for Non-Responders

Following a yearlong trial of Vertex's oral protease inhibitor, telaprevir's high success rate in clearing Hepatitis C from previous non-responders has landed it in the final stretch for FDA approval.

Vertex’s Hepatitis C Drug Helps Sickest Patients Get Relief

By Michelle Fay Cortez and Lisa Rapaport

April 25 (Bloomberg) -- Vertex Pharmaceuticals Inc.’s experimental hepatitis C drug telaprevir wiped out signs of the infection in half of patients with hard-to-treat forms of the disease in a yearlong study.

The Prove 3 trial, presented at the European Association for the Study of the Liver in Copenhagen, found adding the drug to Roche Holding AG’s Pegasys and Copegus improved response to therapy. The study also showed Copegus is essential. Researchers left it out of one arm of the trial in an effort to reduce side effects, and netted lower patient response as well.

The study tracked 453 patients who failed to benefit from previous treatment or suffered a relapse after therapy, giving them few treatment options. Fifty-two percent of those who got therapy including telaprevir for 48 weeks experienced a sustained response -- with no signs of the virus that causes hepatitis C -- compared with 14 percent of those given the Roche drugs alone.

“Previously treated patients who didn’t achieve sustained viral response represent the hardest to treat patient population in physicians’ practices,” said lead investigator Michael Manns, director of gastroenterology, hepatology and endocrinology at the Medical School of Hannover, Germany, in a statement. “This represents an exciting potential medical advance.”

The study, from the second of three phases needed for regulatory approval, was funded by Vertex and its partner, New Brunswick, New Jersey-based Johnson & Johnson.

Final Stage Testing

Studies from the final stage needed for U.S. Food and Drug Administration approval are under way, and should be completed in the first half of next year, said Robert Kauffman, senior vice president of clinical development at Cambridge, Massachusetts-based Vertex, in a telephone interview.

“These are unprecedented results, with the highest sustained viral response rates ever reported,” Kauffman said.

Few patients relapse months after they finish treatment, suggesting a potential cure for those who respond, he said.

“You want to follow patients over the long term just to be sure,” he said. “Based on everything we know, we’re optimistic these patients will maintain their responses.”

Telaprevir is an oral protease inhibitor, which works by targeting an enzyme the virus needs to replicate. The Roche drugs work by an indirect method, bolstering the patient’s immune system and their own ability to fight off the disease.

170 Million Infected

About 170 million worldwide, and 3.4 million in the U.S., have hepatitis C, a liver disease that is spread mainly through contact with the blood of infected patients, according to the World Health Organization. Symptoms include stomach pain, fever and fatigue, and can increase the risk of cirrhosis and death.

“Vertex’s long-term growth story looks more secure with each HCV conference we attend,” Thomas J. Russo, an analyst at Robert W. Baird in Chicago, wrote in an April 24 note to clients.

To contact the reporters on this story: Michelle Fay Cortez in London at mcortez@bloomberg.net; Lisa Rapaport in New York at Lrapaport1@bloomberg.net.

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April 30, 2009

Interferon-Free Drug Combo Effective Against Hepatitis C

An interferon-free combination of four different drugs taken orally demonstrates encouraging initial results for reducing Hepatitis C viral load.

Business - Press Releases: PR Newswire

Saturday, Apr. 25, 2009

Ground-Breaking Combination of All-Oral Agents Demonstrates Potential as Hepatitis C Treatment Regimen

Roche; InterMune; Pharmasset

- Combination of R7227, protease inhibitor, and R7128, nucleoside polymerase inhibitor, shows significant potency in reducing viral load in patients with hepatitis C - NUTLEY, N.J., BRISBANE, Calif., and PRINCETON, N.J., April 25 /PRNewswire-FirstCall -- Roche, InterMune, Inc. (Nasdaq: ITMN) and Pharmasset (Nasdaq: VRUS) today announced the first results from their innovative, interferon-free regimen of direct acting antiviral (DAA) combination therapy for the treatment of patients chronically infected with the hepatitis C virus (HCV)(1). The study combined two oral DAAs, R7227 (also known as ITMN-191) and R7128, for the first time in patients. There were no serious adverse events reported during the 14 days of dosing, and the reductions in levels of HCV RNA were significant.

Results of the INFORM-1 study were presented today during the late-breaker session at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL) in Copenhagen.

The trial, conducted in centers in New Zealand and Australia, is the first to investigate the combination of two oral antiviral medicines in the absence of interferon and ribavirin. The results demonstrated for the first time that the combination of an oral protease inhibitor and an oral nucleoside polymerase inhibitor resulted in significant HCV viral load reduction in patients with HCV. Roche is developing R7227, a protease inhibitor, with InterMune, and R7128, a nucleoside polymerase inhibitor, with Pharmasset.

Further studies will test the activity and safety of the combination of R7227 and R7128 with and without interferon and/or ribavirin. The current standard of care for HCV is a combination of pegylated interferon plus ribavirin, which delivers overall sustained virologic response rates (SVR) of 50-60 percent.

"These are exciting times in our fight against hepatitis C, and the investigation of the innovative oral treatment regimen in INFORM-1, if validated in further study, may radically change future treatment strategies in our patients with chronic HCV infection," said Edward Gane, M.D., Associate Professor, University of Auckland and Director, Auckland Clinical Studies Limited. "The initial results from this study of the R7227/R7128 combination raise hopes of the possibility for an interferon-free treatment regimen, as well as the potential for a shorter, more potent interferon-based regimen."

INFORM-1 Results in Brief

INFORM-1 is a randomized, double-blind, ascending dose Phase I trial which has enrolled a total of 57 patients.

Patients receiving the combination of R7227 and R7128 for 14 days -- without pegylated interferon or ribavirin -- experienced a median reduction in viral levels of -4.8 to -5.2 log(10) IU/mL in the highest doses tested. The addition of R7128 to R7227 resulted in sustained viral load reductions over the dosing period, with aproximately 63 percent of patients experiencing a decrease in viral levels below the quantification limit of the diagnostic assay (less than 40 IU/mL). Furthermore, 25 percent of patients in the highest dosage groups were below the limit of detection of the virus in their blood (less than 15 IU/mL) after 14 days.

- Combination of R7227, protease inhibitor, and R7128, nucleoside polymerase inhibitor, shows significant potency in reducing viral load in patients with hepatitis C - NUTLEY, N.J., BRISBANE, Calif., and PRINCETON, N.J., April 25 /PRNewswire-FirstCall -- In the early low-dose groups, after only three days of dosing, the mean reduction in viral load levels was 0.6 log(10) IU/mL greater with combination treatment (-2.9), compared to the performance of the individual compounds when administered as a single agent (-0.46 and -1.84 for R7128 and R7227, respectively). This suggests an additive effect for the combination.

No treatment-related serious adverse events (SAEs), no dose reductions and no discontinuations were reported in the study. Pharmacokinetic analysis confirmed that there were no drug-drug interactions between the compounds.

Next Steps in the Development Program

The companies are now exploring twice-daily dosing of R7227 and higher total daily doses (600 mg twice-daily and 900 mg twice-daily) than those explored in the first patient cohorts of INFORM-1. The companies also plan to explore the innovative DAA combination therapy in "treatment-experienced" patients with HCV, or those who did not achieve SVR with a previous interferon-based treatment.

Other Clinical Studies with R7227 and R7128

In addition to clinical studies of combination DAA regimens such as those studied in INFORM-1, R7227 and R7128 each are proceeding rapidly in development in combination with Roche's PEGASYS(R) (peginterferon alfa-2a) and COPEGUS(R) (ribavirin). A Phase IIb study with R7128 has now begun, while a Phase IIb study with R7227 is slated to begin in the summer.

The Foundation and Future of HCV Treatment

Combination therapy of pegylated interferon and ribavirin is the current standard of care for HCV. PEGASYS is the leading treatment for HCV, and also is the pegylated interferon therapy of choice for most HCV antiviral agents in development -- including those developed through collaborations with Roche, as well as those developed by other companies. The collaborations with InterMune and Pharmasset position Roche as a leader in developing innovative treatments for HCV.

Dial-In and Webcast Details

InterMune and Pharmasset will host a live webcast of a discussion of the INFORM-1 results from the EASL conference today, Saturday, April 25, 2009, at 7:00 p.m. CEST (1:00 p.m. EDT). Participating in the discussion will be Dr. Ed Gane, principal investigator in the INFORM-1 trial. Members of management from Roche, InterMune and Pharmasset will also be available to answer questions. A live webcast and slide presentation will be available through the Investor Relations pages of both InterMune and Pharmasset at www.intermune.com or www.pharmasset.com, respectively. Alternatively, interested parties may access the discussion and ask questions by dialing 888-799-0528 (U.S. and Canada) or 973-200-3372 (international), conference ID # 95452531. A webcast replay will be available approximately three hours after the call and will be archived at www.intermune.com and at http://www.pharmasset.com.

The companies recommend logging on at least 15 minutes prior to the start of the webcast to ensure adequate time for any software downloads that may be required.

About R7227 (ITMN-191)

R7227 is a potent, macrocyclic inhibitor of HCV NS3/4A protease activity, and has produced multi-log(10) reductions in levels of HCV levels in chronic HCV patients, when administered for 14 days as monotherapy and when combined with PEGASYS and COPEGUS. R7227 was safe and well-tolerated in these studies.

About R7128

R7128, a cytidine nucleoside analog inhibitor of HCV RNA polymerase, is being developed for the treatment of chronic HCV infection. R7128 has shown potent in vivo activity against all of the most common HCV genotypes (1, 2 and 3). R7128 was safe and well-tolerated when given with PEGASYS and COPEGUS for up to 28 days.

About PEGASYS

PEGASYS, in combination with COPEGUS (ribavirin), is indicated for the treatment of adults with chronic HCV who have compensated liver disease and have not previously been treated with interferon alpha. Efficacy has been demonstrated in patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A) and patients with HIV disease that are clinically stable (e.g., antiretroviral therapy not required or receiving stable antiretroviral therapy). In addition, PEGASYS in combination with COPEGUS is the first and only FDA-approved regimen for the treatment of chronic HCV in patients coinfected with HCV and HIV. PEGASYS is the only pegylated interferon indicated for the treatment of adult patients with chronic hepatitis B (HBeAg positive and HBeAg negative chronic hepatitis B who have compensated liver disease and evidence of viral replication and liver inflammation).

PEGASYS is dosed at 180mcg as a subcutaneous injection taken once a week. COPEGUS is available as a 200mg tablet, and is administered orally two times a day as a split dose. Roche has backed PEGASYS with the most extensive clinical research program ever undertaken in HCV, with major studies initiated to advance treatment for HCV patients with unmet needs, including patients co-infected with HIV and HCV, African Americans, patients with cirrhosis, and patients who have failed to respond to previous therapy.

Important Safety Information About PEGASYS

- Combination of R7227, protease inhibitor, and R7128, nucleoside polymerase inhibitor, shows significant potency in reducing viral load in patients with hepatitis C - NUTLEY, N.J., BRISBANE, Calif., and PRINCETON, N.J., April 25 /PRNewswire-FirstCall -- PEGASYS, alone or in combination with COPEGUS, is indicated for the treatment of adults with chronic hepatitis C virus infection who have compensated liver disease and have not been previously treated with interferon alpha. Patients in whom efficacy was demonstrated included patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A).

Alpha interferons, including PEGASYS(R) (Peginterferon alfa-2a), may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping PEGASYS therapy (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS in complete product information).

Use with Ribavirin. Ribavirin, including COPEGUS(R), may cause birth defects and/or death of the fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with ribavirin therapy may result in a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS in complete product information).

PEGASYS is contraindicated in patients with hypersensitivity to PEGASYS or any of its components, autoimmune hepatitis, and hepatic decompensation (Child-Pugh score greater than 6; class B and C) in cirrhotic CHC monoinfected patients before or during treatment. PEGASYS is also contraindicated in hepatic decompensation with Child-Pugh score greater than or equal to 6 in cirrhotic CHC patients coinfected with HIV before or during treatment. PEGASYS is also contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurological and other complications in neonates and infants, which are sometimes fatal. PEGASYS and COPEGUS therapy is additionally contraindicated in patients with a hypersensitivity to COPEGUS or any of its components, in women who are pregnant, men whose female partners are pregnant, and patients with hemoglobinopathies (eg, thalassemia major, sickle-cell anemia).

COPEGUS THERAPY SHOULD NOT BE STARTED UNLESS A REPORT OF A NEGATIVE PREGNANCY TEST HAS BEEN OBTAINED IMMEDIATELY PRIOR TO INITIATION OF THERAPY. Women of childbearing potential and men must use two forms of effective contraception during treatment and during the 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time. If pregnancy should occur during treatment or during 6 months post-therapy, the patient must be advised of the significant teratogenic risk of COPEGUS therapy to the fetus. Healthcare providers and patients are strongly encouraged to immediately report any pregnancy in a patient or partner of a patient during treatment or during 6 months after treatment cessation to the Ribavirin Pregnancy Registry at 1-800-593-2214.

Chronic hepatitis C (CHC) patients with cirrhosis may be at risk of hepatic decompensation and death when treated with alpha interferons, including PEGASYS. During treatment, patients' clinical status and hepatic function should be closely monitored, and PEGASYS treatment should be immediately discontinued if decompensation (Child-Pugh score greater than or equal to 6) is observed. Ischemic and hemorrhagic cerebrovascular events have been observed in patients treated with interferon alfa-based therapies, including PEGASYS. Events occurred in patients with few or no reported risk factors for stroke, including patients less than 45 years of age. Because these are spontaneous reports, estimates of frequency cannot be made and causal relationship between interferon alfa-based therapies and these events is difficult to establish.

The most common adverse events reported for PEGASYS and COPEGUS combination therapy observed in clinical trials were fatigue/asthenia (65 percent), headache (43 percent), pyrexia (41 percent), myalgia (40 percent), irritability/anxiety/nervousness (33 percent), insomnia (30 percent), alopecia (28 percent), neutropenia (27 percent), nausea/vomiting (25 percent), rigors (25 percent), anorexia (24 percent), injection site reaction (23 percent), arthralgia (22 percent), depression (20 percent), pruritus (19 percent) and dermatitis (16 percent).

Serious adverse events in hepatitis C trials included neuropsychiatric disorders (homicidal ideation, suicidal ideation, suicide attempt, suicide, psychotic disorder and hallucinations), serious and severe bacterial infections (sepsis), bone marrow toxicity (cytopenia and rarely, aplastic anemia), cardiovascular disorders (hypertension, supraventricular arrhythmias and myocardial infarction), hypersensitivity (including anaphylaxis), endocrine disorders (including thyroid disorders and diabetes mellitus), autoimmune disorders (including idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, psoriasis, lupus, rheumatoid arthritis and interstitial nephritis), pulmonary disorders (dyspnea, pneumonia, bronchiolitis obliterans, interstitial pneumonitis and sarcoidosis), colitis (ulcerative and hemorrhagic/ischemic colitis), pancreatitis, and ophthalmologic disorders (decrease or loss of vision, retinopathy including macular edema and retinal thrombosis/hemorrhages, optic neuritis and papilledema).

Adverse reactions reported during post-approval use of PEGASYS therapy, with and without ribavirin, include hearing impairment, hearing loss, serious skin reactions, including erythema multiforme major, and infections (bacterial, viral and fungal).

About Roche

About InterMune

InterMune is a biotechnology company focused on the research, development and commercialization of innovative therapies in pulmonology and hepatology. InterMune has a pipeline portfolio addressing idiopathic pulmonary fibrosis (IPF) and hepatitis C virus (HCV) infections. The pulmonology portfolio includes the Phase III program, CAPACITY, which is evaluating pirfenidone as a possible therapeutic candidate for the treatment of patients with IPF and a research program focused on pirfenidone analog ITMN-520. The hepatology portfolio includes the HCV protease inhibitor compound R7227 (ITMN-191), a second-generation HCV protease inhibitor research program, and a research program evaluating a new target in hepatology. For additional information about InterMune and its R&D pipeline, please visit www.intermune.com.

About Pharmasset

Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is on the development of oral therapeutics for the treatment of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Pharmasset is currently developing three product candidates. R7128, an oral treatment for chronic HCV infection, has completed a 4-week clinical trial in combination with PEGASYS plus COPEGUS through a strategic collaboration with Roche, and is initiating a Phase IIb trial. Racivir, which is being developed for the treatment of HIV in combination with other approved HIV drugs, has completed a Phase II clinical trial. PSI-7851, an unpartnered second generation HCV nucleotide analogue recently entered Phase I studies. Additional information is available on the Internet at http://www.pharmasset.com

Forward-Looking Statements

This news release contains forward-looking statements within the meaning of section 21E of the Securities Exchange Act of 1934, as amended, that reflect the companies' judgments and involve risks and uncertainties as of the date of this release, including without limitation the statements related to anticipated product development timelines. All forward-looking statements and other information included in this press release are based on information available to the companies as of the date hereof, and the companies assume no obligation to update any such forward-looking statements or information. Actual results could differ materially from those described in the forward-looking statements.

Factors that could cause or contribute to such differences include, but are not limited to, those discussed in detail under the heading "Risk Factors" in the companies' most recent annual reports on Form 10-K filed with the SEC and in other periodic reports filed with the SEC. The risks and other factors discussed above should be considered only in connection with the fully discussed risks and other factors discussed in detail in the respective Forms 10-K and in the companies' other periodic reports filed with the SEC, all of which are available via their respective web sites at www.intermune.com and .

All trademarks used or mentioned in this release are protected by law.

- About INFORM-1: www.clinicaltrials.gov

(1) "First-In-Man Demonstration Of Potent Antiviral Activity with a Nucleoside Polymerase (R7128) and Protease (R7227/ITMN-191) Inhibitor Combination in HCV: Safety, Pharmacokinetics, and Virologic Results from INFORM-1," Abstract #1046: to be presented at 44th Annual Meeting of the European Association for the Study of the Liver (EASL) in Copenhagen, Denmark, April 22 - 26, 2009.

Contacts:
Linda Dyson
Roche
973-562-2231 (office)
973-986-5973 (mobile)
Linda.Dyson@roche.com

Jim Goff Sr. Director, Corp. Comm. & IR InterMune, Inc. 415-466-2228 jgoff@intermune.com

Richard E. T. Smith, Ph.D. VP, Investor Relations and Corporate Communications Pharmasset 609-613-4181 richard.smith@pharmasset.com

SOURCE Roche; InterMune; Pharmasset

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April 29, 2009

DNA-based Therapeutic Vaccine for Hepatitis C Posts Encouraging Results

Data from a clinical trial brings hope for a DNA-based therapeutic vaccine for Hepatitis C.

First evidence for DNA-based vaccination against chronic hepatitis C

April 23, 2009

The first-proof-of-concept for a DNA-based therapeutic vaccination against chronic hepatitis C was announced today at EASL 2009, the Annual Meeting of the European Association for the Study of the Liver in Copenhagen, Denmark.

In the first clinical trial of a therapeutic vaccination using naked DNA delivered by in vivo electroporation (EP), antiviral effects were shown in patients with hepatitis C (HCV). Researchers hope that this will encourage further clinical development. The data also provide further evidence for the antiviral role of the HCV-specific T cell response.

It is estimated that some 3% of the world's population is infected with HCV. In industrialised countries, hepatitis C accounts for 70% of chronic hepatitis cases. One of the main concerns is that HCV infection remains asymptomatic until advanced stages of the disease.

Clearance of HCV infection correlates with activation of the host T cell response. Therefore, in this study, researchers developed a T cell vaccine based on a codon-optimised HCV non-structural (NS) 3/4A DNA-gene expressed under the control of the cytomegalovirus immediate-early promoter (ChronVac-C®) delivered by in vivo electroporation (EP). A first phase I/IIa clinical trial in HCV infected patients is currently ongoing.

Professor Matti Sallberg of Laboratory Medicine, the Karolinska Institutet, Stockholm, Sweden, who led the study, said: "In 50-80% of adult cases, the immune system fails to eliminate the HCV virus and the disease becomes chronic. Given that only about 50% of HCV infected persons are diagnosed in most developed countries and that two-thirds need to undergo antiviral treatment, this new vaccination has huge implications in terms of the future management of this widespread disease."

In this study, a volume of 0.5 ml saline containing ChronVac-C® DNA was injected at 1 cm depth in the deltoid muscle. This was followed by two 60ms electrical pulses administered using a 1.5 cm four-electrode array (Medpulser DDS; Inovio, CA, US). The study aims were safety, immunogenicity, and effects on the viral load. Twelve treatment naive patients infected with HCV genotype 1 and a viral load <800,000 IU/ml were divided in four groups of 167 µg, 500 µg, and 1,500 µg given as four monthly doses of DNA.

In the 167µg group, no severe side effects were observed, two patients mounted transient T cell responses, and none had a reduced viral load. In the 500µg dose, no severe side effects were observed, and two developed better sustained HCV-specific T cell responses. Simultaneous with these responses, both patients had reductions in the viral load of up to 0.89 log10 and 1.5 log10, respectively. In the third patient, no immune response developed and no clear reductions in the viral load were seen. In the 1,500µg dose, no severe side effects were observed, and one patient developed HCV-specific T cell response. Two patients had reductions in the viral load of up to 1.2 log10 and 2.4 log10, respectively. Thus, 67% (four out of six) of patients in the two highest dose groups had reductions in the viral load exceeding 0.5 log10 lasting for two to >10 weeks. Of these, three had activations of the HCV-specific T cell responses at the time of the reductions in the viral load.

Source : European Association for the Study of the Liver

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April 27, 2009

Hepatitis C Trial on Controlled Release Interferon Underway

Dosing has started for a Phase 2b study of Locteron®, an every-other-week, controlled release, interferon alpha-2b medication to treat Hepatitis C.

Biolex Therapeutics Commences Phase 2B Trial of Locteron(R) in Chronic Hepatitis C

Author: Biolex Therapeutics
Category: Press Release

PITTSBORO, NC -- 04/20/09 -- Biolex Therapeutics, Inc. announced today the commencement of patient dosing in the SELECT-2 Phase 2b trial of its lead product candidate Locteron for the treatment of chronic hepatitis C. Locteron, controlled-release interferon alpha 2b, is designed to improve patient care by providing a more convenient once-every-two week dosing schedule and by reducing the side effects associated with pegylated interferons, the current standard of care, including flu-like symptoms. The Company also announced that the preliminary results of the recently completed United States Phase 2a Locteron trial ("PLUS" trial) will be presented at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL) April 24, 2009 in Copenhagen, Denmark.

The Phase 2b trial is being conducted in the United States and Europe in 100 treatment-naïve, genotype-1, chronic hepatitis C patients. Patients will be randomized into one of four dosing cohorts, the 320, 480 or 640 µg dose of Locteron (administered once every two weeks) or a control arm consisting of PEG-Intron® (administered every week), with all patients receiving weight-based ribavirin. Patients will be treated for 48 weeks and will be followed for an additional 24 weeks to determine the sustained virologic response (SVR) rate. The interim results after 12 weeks of treatment are expected to be used as the basis for the selection of the Locteron dose(s) for Phase 3 trials.

"The primary objective of the SELECT-2 Phase 2b trial is to identify one or more doses of Locteron for advancement to Phase 3 trials based on an evaluation of viral response and safety and tolerability, including reductions in flu-like symptoms," said Mr. Jan Turek, Biolex's President and Chief Executive Officer. "We believe Locteron to be a valuable asset as it is the only controlled-release interferon alpha under development, and interferon alpha serves as the current standard of care for hepatitis C and provides the backbone for each of the new anti-viral candidates under development. Market research confirms that there is a substantial commercial opportunity for Locteron if a tolerability advantage is demonstrated in more advanced clinical testing."

Locteron is an investigational therapeutic candidate and has not been approved for sale by the United States Food and Drug Administration or by any international regulatory agency.

Locteron Overview

Locteron is a controlled-release interferon alpha designed to improve patient care in the treatment of hepatitis C through a more favorable side-effect profile and dosing convenience compared to existing pegylated interferon products. In contrast to Locteron's controlled-release mechanism, the currently approved products, Pegasys® and PEG-Intron®, and the investigational product Albuferon®, are immediate-release products that lack a controlled-release mechanism. Interferon alpha serves as the foundation of current combination therapy for hepatitis C patients, and all major hepatitis C drug candidates currently in clinical trials are being studied in combination with interferon alpha. It is estimated that worldwide sales of interferon products for the treatment of hepatitis C will approach $6 billion by 2016.

Locteron combines BLX-883, a recombinant interferon alpha produced by Biolex in its patented LEX System(SM), with PolyActive®, an advanced controlled-release drug delivery technology developed by OctoPlus N.V. of Leiden, the Netherlands. Locteron is configured to allow dosing once every two weeks, more convenient than Pegasys® and PEG-Intron®, each of which require dosing every week. More importantly, Locteron's controlled-release mechanism results in the gradual release of interferon alpha 2b to patients over the duration of two weeks and avoids the early peak plasma levels of the active interferon that characterize the pegylated interferons and Albuferon. This controlled-release mechanism is designed to reduce the frequency, duration and severity of side effects, including flu-like symptoms, commonly experienced by patients treated with pegylated interferons and with Albuferon. The Company has completed three clinical trials of Locteron, and the results of the SELECT-1 Phase 2a trial were presented at the 43rd Annual Meeting of the European Association for the Study of the Liver in April 2008.

About Biolex Therapeutics

Biolex is a clinical-stage biopharmaceutical company that uses its patented LEX System(SM) to develop hard-to-make therapeutic proteins and to optimize monoclonal antibodies. The LEX System is a novel technology that genetically transforms the aquatic plant Lemna to enable the production of biologic product candidates. The company's product candidates are designed to provide superior efficacy/tolerability profiles and to address large, proven pharmaceutical markets. Biolex's lead product candidate, Locteron®, is in Phase 2b clinical testing for the treatment of chronic hepatitis C. Biolex has also developed two other product candidates that capitalize on the benefits of the LEX System which it is advancing toward clinical trials: BLX-155, a direct-acting thrombolytic designed to dissolve blood clots in patients; and BLX-301, an anti-CD20 antibody it is optimizing for the treatment of non-Hodgkin's B-cell lymphoma and other diseases.

Contacts:
Media:
Michelle Linn
Linnden Communications
508-362-3087
Email Contact

Investors:
Dale Sander
Chief Financial Officer
858-663-6993
Email Contact

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phase-2b,790741.shtml

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April 17, 2009

HCV Combination Therapy Approved for Non-Responders

Already approved in Europe and the United States, Viraferonpeg combination therapy is now approved for re-treating Hepatitis C non-responders in India.

Schering-Plough wins Indian approval for hepatitis C combination therapy

Published:13-April-2009

By Datamonitor staff writer

Viraferonpeg, the pegylated interferon therapy in combination with Rebetol

Schering-Plough's majority owned affiliate in India, Fulford India, has received approval for its Viraferonpeg, the pegylated interferon therapy in combination with Rebetol, for re-treating adult patients with chronic hepatitis C whose prior treatment with interferon alpha and ribavirin combination therapy or interferon alpha monotherapy did not result in a sustained response.

The approval is based on results from the clinical study (EPIC3) in which 1,336 patients with moderate-to- severe fibrosis or cirrhosis who failed previous treatment with combination alpha interferon/ribavirin therapy were retreated with Viraferonpeg combination therapy.

In this study, virological response at week 12 of treatment was shown to be an important predictor for achieving a sustained virological response (SVR), with 57% of patients who had undetectable virus (HCV- RNA) at week 12 going on to achieve SVR with a 48-week course of therapy.

With this local approval in India, Viraferonpeg can now be used for re-treatment of a large and growing number of patients who failed previous hepatitis C (HCV) therapy and are in need of viable treatment options.

Viraferonpeg combination therapy is approved for re-treatment of HCV patients in Europe and US, and is the first pegylated interferon combination therapy to be approved for the re-treatment of chronic hepatitis C by the EU and FDA.

KG Ananthakrishnan, managing director of Fulford India, said: "The approval of Viraferonpeg for the re-treatment of chronic Hepatitis offers hope to millions in India and highlights Schering-Plough's steadfast commitment to ongoing research in the field of virology, with the aim of improving the health and quality of life for patients."

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URL for Article Source:
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schering_plough_wins_indian_approval_for_hepatitis_c_combination_
therapy_130409

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April 16, 2009

Insight Into Clearing the Hepatitis B and C Viruses

By investigating co-infection and interferon therapy, two Italian studies look into the future of Hepatitis B and Hepatitis C therapy.

New Studies Examine Elimination Of Hepatitis B And C

ScienceDaily (Apr. 10, 2009) — Two new studies in the April issue of Hepatology explore the ways that hepatitis B virus (HBV) and hepatitis C virus (HCV) can be cleared from patients’ bodies.

Both HBV and HCV are global health problems. They can lead to cirrhosis and liver cancer and they cause millions of deaths each year. Treatments to contain or cure these infections have been difficult to find. Researchers continue to explore potential therapies and the immune system response to the diseases.

The first new study sheds light on the immunological response to coinfection with HBV and HCV. Researchers led by Evangelista Sagnelli of Naples, Italy, report that for patients with chronic HCV, HBV superinfection can lead to clearance of the HCV.

They compared 29 HCV patients to 29 people, matched by age, gender and risk factors, who did not have HCV. All of the patients developed acute HBV during the same time period. The patients with HCV were more likely to have a severe course of illness, and one died of liver failure. However, nearly a quarter (six out of 24) emerged HCV-free.

“Extensive acute hepatocellular necrosis, although life-threatening, may lead to a clearance of chronic HCV infection,” the authors report. Still, the severity of acute HBV in HCV patients raises “the concern that this clinical event could become an emerging health care problem in countries with a wide spread of both HBV and HCV infection,” they write.

“Further efforts should be made to extend the use of HBV vaccination in patients with chronic HCV infection” they also suggest.

The second study, headed by Maurizia Brunetto of Pisa, Italy, recommends interferon-based therapies as a first-line approach for patients with chronic HBV, because these have the best chance of clearing hepatitis B virus surface antigen (HBsAg). The reduction of HBsAg serum levels leading to HBsAg clearance is the hallmark of a newly achieved immune control of the infection by mean of a significant reduction of virus infected hepatocytes.

The researchers retrospectively investigated the relationship between treatment regimens and changing levels of HbsAg in 386 patients in a multinational study.

“Significantly more patients treated with peginterferon alfa-2a (21 percent) or peginterferon alfa-2a plus lamivudine (17 percent) achieved HBsAg levels under 100 IU/mL at the end of treatment compared with lamivudine (1 percent),” they report.

“HBsAg clearance represents the best possible and closest to cure outcome of antiviral therapy in patients with chronic hepatitis B, but is realistic almost exclusively among patients receiving interferon-based regimens, which are recommended as a first-line therapeutic approach,” they conclude. Interferon therapy switches the chronic active hepatitis B patient in the non-active HBV carrier who lose serum HBsAg during the years after the end of therapy. If the case occurs before the development of liver cirrhosis it endows the patient with the same life expectancy of the non-HBV infected subject.

Article: “HBV Superinfection in HCV Chronic Carriers, A Disease That Is Frequently Severe But Associated With the Eradication of HCV.” Sagnelli, Evangelista; Coppola, Nicola; Pisaturo, Mariantonietta; Masiello, Addolorata; Tonziello, Gilda; Sagnelli, Caterina; Messina, Vincenzo; Filippini, Pietro. Hepatology; April 2009.

Article: “Hepatitis B Virus Surface Antigen Levels—A Guide to Sustained Response to Peginterferon Alfa-2a in HBeAg-negative Chronic Hepatitis B.” Brunetto, Maurizia; Moriconi, Francesco; Bonino, Ferruccio; Lau, George; Farci, Patrizia; Yurdaydin, Cihan; Piratvisuth, Teerha; Luo, Kangxian; Yuming, Wang; Hadziyannis, Stephanos; Wolf, Eva; McCloud, Philip; Batria, Richard; Marcellin, Patrick. Hepatology; April 2009.

Journal references:

1. Sagnelli, Evangelista; Coppola, Nicola; Pisaturo, Mariantonietta; Masiello, Addolorata; Tonziello, Gilda; Sagnelli, Caterina; Messina, Vincenzo; Filippini, Pietro. HBV Superinfection in HCV Chronic Carriers, A Disease That Is Frequently Severe But Associated With the Eradication of HCV. Hepatology, April 2009

2. Brunetto, Maurizia; Moriconi, Francesco; Bonino, Ferruccio; Lau, George; Farci, Patrizia; Yurdaydin, Cihan; Piratvisuth, Teerha; Luo, Kangxian; Yuming, Wang; Hadziyannis, Stephanos; Wolf, Eva; McCloud, Philip; Batria, Richard; Marcellin, Patrick. Hepatitis B Virus Surface Antigen Levels -- A Guide to Sustained Response to Peginterferon Alfa-2a in HBeAg-negative Chronic Hepatitis B. Hepatology, April 2009

Adapted from materials provided by Wiley-Blackwell.

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March 23, 2009

Inhibiting the Hepatitis C Virus

Opening up new treatment possibilities, researchers from Scripps Institute have found molecules that prevent Hepatitis C viral production.

Study may lead to anti-hepatitis-C drug

JUPITER, Fla., Mar 12, 2009 (UPI via COMTEX) -- U.S. researchers say they have identified key molecules that inhibit viral production in a study that might lead to new treatments for hepatitis C.

The research, led by Professor Donny Strosberg of the Scripps Institute in Jupiter, Fla., describes peptides (molecules of two or more amino acids) derived from the core protein of hepatitis C. The team found the peptides inhibit not only chemical reaction of the core protein -- the joining of two identical subunits -- but also production of the actual virus.

"We went for the simplest solution, taking a peptide from core to see if we could block the interaction," Strosberg said. "And it did."
The study is to be published by the Journal of General Virology and is available in the journal's March 4 pre-print online edition.

www.upi.com

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March 02, 2009

Human Trial Begins for Hepatitis C Oral Protease Inhibitor

Because it showed potency against Hepatitis C in vitro, Abbott and Enanta Pharmaceuticals are beginning their first human trial for ABT-450. If this protease inhibitor fares well in healthy humans, it will progress to the next stage of testing.

Abbott and Enanta initiate Phase I hepatitis trial

Published: 23-February-2009

By Datamonitor staff writer

Abbott and Enanta Pharmaceuticals, a R&D company, have announced the advancement of their hepatitis C virus collaboration with a first-in-human study evaluating ABT-450, an oral protease inhibitor for the treatment of chronic HCV.

The objectives of the trial include assessment of safety, tolerability and pharmacokinetics. ABT-450 was discovered as part of a worldwide alliance between Abbott and Enanta to discover, develop and commercialize protease inhibitors for the treatment of hepatitis C virus (HCV).

The Phase I, double-blind, placebo-controlled study for ABT-450 is a single, ascending oral dose trial in healthy volunteers.

Jay Luly, president and CEO of Enanta, said: "ABT-450 demonstrated favorable potency in vitro across various HCV genotypes and highly resistant strains. We look forward to working with Abbott to advance ABT-450, and to our building a pipeline of HCV protease inhibitors that addresses this widespread disease."

Abbott is a health care company committed to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. In addition to developing HCV therapies, Abbott also offers laboratory tests for patient diagnosis, blood screening tests for hospitals and blood banks, and molecular diagnostic tests to measure HCV viral load and resistance.

Enanta Pharmaceuticals is a research and development company that uses its novel chemistry approach and drug discovery capabilities to create best-in-class small molecule drugs in the anti-infective field. Enanta is developing novel protease, polymerase and cyclophilin-based inhibitors targeted against the Hepatitis C virus (HCV). Additionally, the company has created a new class of macrolide antibiotics, called Bicyclolides, which overcomes bacterial resistance.

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February 03, 2009

Hepatitis C Vaccine on the Horizon

Learn why Rockefeller University scientists' recent discovery on how to infect mice with Hepatitis C could lead to a necessary HCV vaccine.

Discovery Could Lead To A New Animal Model For Hepatitis C

ScienceDaily (Jan. 28, 2009) — During its career, the potentially fatal hepatitis C virus has banked its success on a rather unusual strategy: its limitations. Its inability to infect animals other than humans and chimpanzees has severely hampered scientists in developing a useful small animal model for the disease.

But now, in a breakthrough published in the journal Nature, Rockefeller University scientists have identified a protein that allows the virus to enter mouse cells, a finding that represents the clearest path yet for developing a much-needed vaccine as well as tailored treatments for the 170 million people across the globe living with the tenacious, insidious and rapidly changing virus.

By using a genetic screen, the group, led by Charles M. Rice, head of the Laboratory of Virology and Infectious Disease, identified a human protein, called occludin, that makes mouse cells susceptible to the virus. The discovery means that scientists now have the complete list of cellular factors — a total of four — that are required for the virus to enter nonhuman cells.

The hepatitis C virus exclusively targets human liver cells, suggesting that these cells express genes that allow uptake of the virus, genes that are not expressed in other human and nonhuman cells, explains Rice. In past years, three proteins — CD81, CLDN1 and SR-BI — were identified as having key roles in shuttling the virus into cells, but something was clearly missing. Rice’s group found that even when they engineered mouse cells to overexpress all three proteins, the cells still denied the virus entry.

The discovery of occludin, however, has changed that. When Rice and his colleagues engineered mouse and human cell lines to express all four proteins, they showed that each cell line became infectible with the virus. To further establish occludin’s role as a required entry factor, the group showed that human liver cells naturally express high levels of occludin, and that by silencing its expression, they could give these once highly susceptible liver cells the ability to completely block infection.

“You know, you sort of have to get lucky,” says Rice, who is also Maurice R. and Corinne P. Greenberg Professor at Rockefeller. “You’ve got these three factors you know are important, but you could have 10 other human factors that could have been necessary for hepatitis C virus entry. This work shows that’s not the case.”

In their DNA screen, the team, including Alexander Ploss, a research associate in the lab, and Matthew J. Evans, currently at Mount Sinai School of Medicine in New York, first cloned all the genes that were expressed in liver cells and then delivered them to mouse cells. “Then, going through an iterative screening process, we honed in on the genes that made the mouse cells permissive,” says Ploss, who spearheaded the project with Evans.

Since mice and humans each have a species-specific version of the four factors, the group used hamster cells to see which combination of factors did the best job at making the cells infectible. They found that in the case of two of the proteins, occludin and CD81, only the human versions worked; for SR-BI and CLDN1, the human and mouse versions did an equally good job. These experiments not only suggest that there may be more than one potential animal model, but also that there are several specific combinations of entry factors that could generate them.

“This work provides a clear foundation upon which we can now begin to construct an animal model for the uniquely human pathogen,” says Rice. “This is only a first step but in terms of creating an animal model for hepatitis C, it’s a big leap forward.”

Journal reference:

1. Ploss et al. Human occludin is a hepatitis C virus entry factor required for infection of mouse cells. Nature, January 28, 2009; DOI: 10.1038/nature07684

Adapted from materials provided by Rockefeller University.

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January 19, 2009

Future Drug Treatments for HCV: Inhibiting the p7 Protein

By targeting p7, a protein that helps Hepatitis C spread, British researchers believe that combination therapies will be more effective at defeating the virus.

Hepatitis C virus: Combination therapies may be effective against hepatitis C virus

Researchers at the University of Leeds have found that combination therapies similar to those used for HIV patients may be the best way of treating hepatitis C virus (HCV).

A study of a protein called p7, has shown that differences in the genetic coding of the protein between virus strains - known as genotypes - alter the sensitivity of the virus to drugs that block its function.

The p7 protein assists the spread of HCV around the body and is a promising target for new drug treatments for the virus.

This role of the protein was discovered in 2003 by Dr Steve Griffin with Professors Mark Harris and Dave Rowlands of the University’s Faculty of Biological Sciences.

And their study has shown that inhibiting p7 with drugs can prevent the spread of HCV.

“One of the challenges in finding treatments for viruses is their ability to constantly change their genetic makeup. Our research shows there can’t be a one-size-fits-all approach to treating HCV with p7 inhibitors in the future. We believe combination treatments will work much more efficiently, as they take into account the variability of the p7 protein,” Harris said.

The researchers examined the response of HCV to a panel of compounds including the well-known anti-viral drug, rimantadine, which targets a similar protein in the flu virus.

They found that the drug’s effectiveness was altered depending on the genetic makeup of the p7 protein.

Dr Griffin said: “We ‘borrowed’ rimantadine to test its effects because p7 behaves similarly to a protein found in the flu virus. Although rimantadine works well in the laboratory, we now need to develop new drugs specifically targeted against p7 that we can take forward for future therapies.” (ANI)

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December 18, 2008

Treatment Approved for Kids With Hepatitis C

Instead of prescribing the drugs for "off-label use," pediatricians can now feel more confident when treating children with Hepatitis C. Schering-Plough's Rebetol and PEG-Intron have been officially approved by the FDA for treating Hepatitis C in kids aged 3 to 17.

Schering-Plough hepatitis C drug approved for kids

By LINDA A. JOHNSON

TRENTON, N.J. (AP) — The first high-tech, long-acting treatment for hepatitis C in children, a two-drug combination from Schering-Plough Corp., has been approved by the Food and Drug Administration.

Schering-Plough said Friday that FDA had approved sales of a treatment combining its antiviral pill, Rebetol, with its PEG-Intron, an advanced, genetically engineered version of the immune system protein interferon, for children age 3 to 17 infected with the hepatitis C virus.

An estimated 130,000 American children are infected with hepatitis C, with most of them acquiring it from an infected mother while in the womb. Some adolescents are infected with the liver-destroying virus through illegal drug use that involves sharing contaminated needles or by getting tattoos or body piercings at establishments with poor hygiene.

Many adults and even some children don't know they are infected because hepatitis C can display no obvious symptoms for years, but it often is spotted when a patient has blood testing for something else.

Earlier versions of interferon drugs, which are widely used in adults to treat chronic hepatitis C, had to be injected three times a week. PEG-Intron, available for several years now, has a technology called pegylation that allows the drug to circulate in the bloodstream much longer.

"This treatment is a little more effective than (the older one) and only involves one shot a week," said Dr. Jean P. Molleston, a pediatric hepatitis C expert at Indiana University School of Medicine who has participated in industry-funded research.

She said FDA approval is important because while some hepatitis specialists have prescribed the pegylated interferon to children and adolescents off label — without official approval, which is legal — many more doctors will feel comfortable doing so now, given the potentially serious side effects of the drugs.

Until now, only Schering-Plough's older interferon drug, Intron A, was officially approved for children in this country. The new approval includes a liquid version of ribavirin for younger children.

Patient testing that led to the approval showed the virus was cleared from 55 percent of the children with the most difficult-to-treat strains of hepatitis C, most of whom had a strain called genotype 1, the type carried by about 70 percent of U.S. hepatitis C patients. Children in that arm of the study were treated for just under a year. In children with less-common, less-resistant strains, 96 percent had the virus cleared from their blood; they were treated for six months.

The study, which included a total of 107 children, was funded by Schering-Plough, which is based in Kenilworth, N.J.

While 55 percent seems disappointing, Molleston noted that the first interferon drugs helped only 15 of patients.

Testing of the older Intron A found it worked in only 36 percent of children with the toughest strain and in 81 percent with easier-to-treat strains.

Children with hepatitis C should be treated by doctors familiar with these drugs because of their serious side effects, some of which require dose adjustments, and very young children should not get them, Molleston said.

She previously participated in research for Schering-Plough and recently participated in a hepatitis C study of a rival drug for children, not yet approved, from the Roche Group.

Ribavirin causes anemia and can cause birth defects or kill a fetus, so pregnancy must be avoided in both female patients and female partners of male patients taking it.

PEG-Intron's side effects include weight loss and stunted growth, which can persist for months after treatments, as well as fever, vomiting, headaches, anorexia, fatigue and a drop in infection-fighting white blood cells.

Even so, "children tolerate these drugs much better than adults," Molleston noted.

According to Schering-Plough, only 2 percent of children in the study stopped treatment early.

Schering-Plough shares rose 83 cents, or 5.2 percent, to close at $16.89 Friday. The company's shares are set be added to the S&P 100 Index after trading closes.

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December 16, 2008

Improving Chronic Hepatitis Outlook: Umbilical Cord Blood

A potential alternative to liver transplant surgery, stem cells from umbilical cord blood may be the solution that those living with chronic hepatitis have been looking for.

by Nicole Cutler, L.Ac.

Once chronic hepatitis has progressed to the end stages of liver disease, there is only one medically accepted option for a person’s recovery. Despite organ transplantation currently being the only choice for helping someone with a non-functioning liver, researchers from Spain are bringing another avenue of hope to those with end stage liver disease. By finding that umbilical cord blood may offer an effective alternative to liver transplants and a potential strategy to treat chronic hepatitis, Spanish scientists could have forever changed the outlook of chronic hepatitis.

About Umbilical Cord Blood
Harvested from the umbilical cord right after a baby is born, stem-cell containing umbilical cord blood is retrieved after the cord has been clamped and cut. Highly coveted by modern medicine, stem cells have the ability to grow into any one of the body’s specialized cells.

Although they are concentrated in cord blood, few stem cells are collected from this source because the total amount of blood from an umbilical cord is small. Despite the challenge of obtaining the quantity needed, stem cells from the umbilical cord have exceptional applications because they are unlikely to cause a graft-versus-host disease after a transplant.

Cord blood cell transplants are already becoming common as a therapy for diseases of the blood. While stem cells from umbilical cord blood appear to be a medicinal panacea, obstacles ranging from possible side effects to political opposition have thwarted their full therapeutic potential.

Cord Blood Stem Cells for the Liver
Fueled by encouraging research that surfaced five years ago, a recently conducted study has demonstrated that stem cells obtained from umbilical cord blood offer real hope for those with chronic hepatitis.

· The Earlier Research – Appearing in the journal Blood in 2003, Xiuli Wang and coworkers transplanted specialized stem cells obtained from umbilical cord and bone marrow into immuno-deficient mice to evaluate a stem cell-based treatment strategy for liver disease. Based on their expression following liver damage, the researchers concluded that bone marrow and umbilical cord stem cells should be considered as an effective treatment strategy for liver diseases.

· Recent Research – To be published in an upcoming issue of Cell Transplantation, a collaborative study conducted by Spanish scientists concluded that mononuclear blood cells derived from the human umbilical cord blood may be useful in the treatment of liver disease, such as hepatitis. The researchers introduced human umbilical cord blood cells through the hepatic portal vein of mice with induced hepatitis. Subsequently, they found a significant improvement in both histological damage and the hepatic function of the animals following cell transplantation.

Today, the need for donor livers far outpaces the supply as more people with chronic hepatitis reach the end stages of liver disease. If future studies using stem cells from umbilical cord blood continue to prove their effectiveness against liver disease, the Spanish research results announced in July of 2008 will be heralded as a major advancement in the field of regenerative hepatic medicine. In addition to the prestige this success could bring, stem cells from umbilical cord blood could become the victor over chronic hepatitis that we’ve all been waiting for.

References:

http://bloodjournal.hematologylibrary.org/cgi/content/abstract/2002-05-1338v1, Albumin expressing hepatocyte-like cells develop in the livers of immune-deficient mice transmitted with highly purified human hematopoietic stem cells, Xiuli Want, et al., Retrieved July 20, 2008, Blood, American Society of Hematology, December 2002.

http://ngm.nationalgeographic.com/ngm/0507/feature1/, The Power to Divide: Stem Cells, Rick Weiss, Retrieved July 20, 2008, National Geographic Society, 2008.

http://news.nationalgeographic.com/news/pf/96995126.html, Umbilical Cord Blood: The Future of Stem Cell Research?, Erica Lloyd, Retrieved July 20, 2008, National Geographic Society, April 2006.

http://prensa.ugr.es/prensa/research/verNota/prensa.php?nota=552, Scientists use stem cells from the umbilical cord to treat hepatic diseases, Luis G Fontana, Retrieved July 17, 2008, University of Granada, 2008.

http://www.bchealthguide.org/kbase/topic/special/uq1027spec/sec1.htm, Umbilical Cord Blood Stem Cells, Retrieved July 20, 2008, Healthwise, Incorporated, 2008.

http://www.medinewsdirect.com/?p=533, Umbilical Cord Blood Derived Stem Cells Used to Treat Liver Disease, Retrieved July 17, 2008, MediNEWS.Direct!, July 2008.

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December 04, 2008

Hep C Study Reveals Taribavirin a Good Alternative to Ribavirin

At the end of a 48-week, Phase IIb study, taribavirin shows similar effectiveness as ribavirin in reducing Hepatitis C viral load. However, participants taking taribavirin had a significantly lower rate of anemia.

Valeant reports encouraging results from Phase IIb hepatitis study

25th November 2008

By Staff Writer

Valeant Pharmaceuticals, a multinational specialty pharmaceutical company, has reported promising results at end of treatment, week 48 analysis point in the Phase IIb clinical trial for its antiviral compound, taribavirin, a prodrug of ribavirin in development for the treatment of chronic hepatitis C in conjunction with a pegylated interferon.

Similar to the treatment week 12 results reported earlier in 2008, the 48-week viral response data continue to show comparable reductions in viral load for weight-based doses of taribavirin and ribavirin. The anemia rate was statistically significantly lower for patients receiving taribavirin in the 20mg/kg and 25mg/kg arms versus the ribavirin control arm.

The Phase IIb trial is a US multi-center, randomized, parallel, open-label study in 278 treatment-naive, genotype 1 patients evaluating taribavirin at 20 mg/kg, 25 mg/kg, and 30 mg/kg per day in combination with pegylated interferon alfa-2b. The control group is being administered weight-based dose ribavirin (800/1000/1200/1400mg daily) and pegylated interferon alfa-2b. Overall treatment duration is 48 weeks with a post-treatment follow-up period of 24 weeks.

Michael Pearson, chairman and CEO of Valeant, said: "We believe that taribavirin will be a promising alternative to ribavirin in the treatment of chronic hepatitis C and, with Valeant's strategic shift away from the infectious disease market, we plan to out-license this compound in order to maximize its potential for these patients."

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Schering-Plough Developing Potent Protease Inhibitor for Hepatitis C

An ongoing Phase IIa study on Schering-Plough's next generation Hepatitis C protease inhibitor is encouraging. According to the company, SCH 900518 is 10 times more potent than other medications in this class and is active against highly resistant Hepatitis C strains.

Schering-Plough to develop new oral hepatitis drug

25th November 2008

By Staff Writer

Schering-Plough, a science-based healthcare company, has announced that it is developing a highly potent next-generation oral hepatitis C protease inhibitor that has future best-in-class potential.

As part of its long-term commitment to hepatitis C therapy, Schering-Plough is developing SCH 900518 (518), a next-generation hepatitis C virus (HCV) protease inhibitor. A Phase IIa study with 518, known as the Next-1 study, is currently ongoing.

The company said that 518 has been shown to be 10 times more potent in-vitro than other protease inhibitors currently in Phase III development and has the potential for once daily dosing. The protease inhibitor also has shown decreased emergence of resistance in vitro. Given its pharmacokinetic profile, the company anticipates that 518 may be active against some HCV strains that are resistant to other protease inhibitors.

Phase I proof of concept studies with 518 in treatment-naive patients and those who failed prior treatment, both as monotherapy and in combination with peginterferon, demonstrated enhanced antiviral activity, with up to 4log10 and 5log10 decreases in circulating HCV, respectively, the company said.

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November 24, 2008

ChronVac-C Reducing HCV Viral Load Up to 99%

Although it is early in the process and only involves a few subjects, interim trial results for ChronVac-C show extremely high percentages of Hepatitis C viral load reduction.

Hepatitis C Therapeutic DNA Vaccine Delivered by Inovio Biomedical's Electroporation Technology Reduces Viral Load by Up to 99.7%

Clinical Data Presented at Annual Scientific Meeting of the American Association for the Study of Liver Diseases

SAN DIEGO, Nov 17, 2008 (BUSINESS WIRE) -- Inovio Biomedical Corporation (INO 0.22, +0.04, +20.2%), a leader in enabling the development of DNA vaccines using electroporation-based DNA delivery, announced today that its partner, Tripep AB, reported positive additional interim results from its ongoing phase I/II clinical study of its therapeutic DNA vaccine against hepatitis C virus (HCV). This vaccine is being delivered using Inovio's electroporation-based DNA delivery system. In the third and highest dose cohort of the study, two of three subjects demonstrated reductions in viral load of 93% and 99.7%. Previously reported middle dose cohort results demonstrated an 87% and 98% reduction in HCV in two of three subjects, while no anti-viral effect was observed in the low dose cohort. No safety issues have been noted to date in the trial. These data suggest a potential dose response of the vaccine and support the inclusion of three additional subjects in the high dose cohort.

These data were presented by Dr. Matti Sanllberg of Tripep at the recent American Association for the Study of Liver Diseases meeting held in San Francisco.

Avtar Dhillon, MD, Inovio's president and CEO, stated: "We continue to be encouraged by the data flowing out of the ChronVac-C study. This promising DNA vaccine candidate, in which Inovio has an ownership position, is one of the more advanced clinical vaccine candidates in the HCV field. ChronVac-C was designed to play a role as a first-line therapy or as an adjunct to existing therapies."

About ChronVac-C

ChronVac-C(R) is a therapeutic DNA-based vaccine given to individuals already infected with the hepatitis C virus with the aim of clearing the infection from the liver by boosting the body's immune response against the virus. Inovio's electroporation technology is being used to deliver the vaccine and is intended to enhance the potency of the DNA vaccine. This clinical study is being conducted at the Infectious Disease Clinic and Center for Gastroenterology at the Karolinska University Hospital in Huddinge and Solna, respectively, in Sweden. The intended enrollment of 12 patients is being divided into four groups, three with increasing doses of ChronVac-C and the fourth at the maximum tolerable dose. Each patient receives four vaccinations one month apart. After the last vaccination, patients are followed for another six months. The study's main purpose is to assess safety. It is also testing whether the treatment boosts the immune response (immunogenicity) to HCV and its effect on virus replication in the liver.

About Inovio Biomedical Corporation

Inovio Biomedical is focused on developing DNA vaccines for cancers and infectious diseases using its novel method for DNA delivery -- electroporation -- which uses brief, controlled electrical pulses to increase cellular uptake of useful biopharmaceuticals. Initial human data has shown that Inovio's electroporation-based DNA delivery technology can significantly increase gene expression and immune responses from DNA vaccines. Immunotherapy partners include Merck, Wyeth, Vical, University of Southampton, Moffitt Cancer Center, the U.S. Army, National Cancer Institute, and International Aids Vaccine Initiative. Inovio's technology is protected by an extensive patent portfolio covering in vivo electroporation. The company has entered into a definitive merger agreement with VGX Pharmaceuticals. More information is available at www.inovio.com.

This press release contains certain forward-looking statements relating to our plans to develop our electroporation drug and gene delivery technology. Actual events or results may differ from our expectations as a result of a number of factors, including the uncertainties inherent in clinical trials and product development programs (including, but not limited to, the fact that pre-clinical and clinical results referenced in this release may not be indicative of results achievable in other trials or for other indications and that results from one study may not necessarily be reflected or supported by the results of other similar studies), the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of Inovio's technology as a delivery mechanism, the availability or potential availability of alternative therapies or treatments for the conditions targeted by Inovio or its collaborators, including alternatives that may be more efficacious or cost-effective than any therapy or treatment that Inovio and its collaborators hope to develop, evaluation of potential opportunities, issues involving patents and whether they or licenses to them will provide Inovio with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether Inovio can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of our technology by potential corporate or other partners or collaborators, capital market conditions, and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2007, our 10-Q for the nine months ended September 30, 2008 and other regulatory filings from time to time. There can be no assurance that any product in our product pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proved accurate.

SOURCE: Inovio Biomedical Corporation

Investors:
Inovio Biomedical
Bernie Hertel, 858-410-3101

Media:
Ronald Trahan Associates Inc.
Ron Trahan, 508-359-4005, x108

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November 14, 2008

Who Will Respond to Hepatitis C Treatment

The relatively new field of proteomics may be able to predict who will respond to Hepatitis C therapy - before treatment even begins.

by Nicole Cutler, L.Ac.

Of the approximately four million Americans infected with chronic Hepatitis C, only about half will benefit from Hepatitis C’s current standard of therapy – interferon and ribavirin. Considering the enormous health and financial tolls this treatment takes on its recipients, clinicians are finding it increasingly important to identify who will respond to the medications early into the treatment regime. However, a new field on the cutting edge of medical technology may have discovered a way to predict who will respond to standard Hepatitis C therapy before the drugs are even started.

Researchers from the Duke University Clinical Research Institute found a similarity among those with Hepatitis C who are among the 50 percent who do not respond to interferon-ribavirin combination therapy. Presented October 31, 2008 at the annual meeting of the American Association for the Study of Liver Disease, the Duke researchers used proteomics to identify specific proteins that foretold the likelihood of Hepatitis C treatment success. The data for this research was derived from the following:

· Blood samples from 30 patients with Hepatitis C were examined.
· Ten of the samples had genotype I and were cured with the standard therapy.
· Ten of the samples had genotype I and did not respond to standard therapy.
· Ten of the samples had genotype 2 or 3 and were cured with the standard therapy.

With 90 percent accuracy, three clusters of proteins in the blood samples were found to predict who would respond to therapy and who would not. Dubbed a ‘protein signature,’ those with the cluster of proteins indicative of non-responders could be directed towards other treatment approaches. Thus, individuals with this non-responder protein signature could be saved from many months of side-effect ridden and costly treatment with interferon and ribavirin.

The importance of this research is summed up by senior study author Dr. John McHutchison, “Those of us who treat patients with Hepatitis C know that treatment can be very difficult, in terms of side effects, and most patients need to be in therapy for almost a year. When treatment demands this much commitment, it would be nice if we had something to help us – and our patients – decide in advance who is most likely to benefit, and who should try other options.”

Art Moseley, director of the proteomics laboratory in the Duke Institute for Genome Science & Policy gives those who have or treat Hepatitis C even more to look forward to, “We still have to figure out which protein pathways these clusters are associated with. That, in turn, may yield information that could lead to new treatment options or more informed treatment decisions using current therapies.”

Background on Proteomics
The completed human genome published in 2003 contained between 30,000 and 35,000 genes, far fewer than the 100,000 genes predicted by scientists when the project began in the mid-1990s. Those genes contain the recipes for between one million and five million proteins. While the genes that compose the human genome provide the building blocks for who we are, the gene’s proteins directly regulate all of our cell’s functions.

Defined in 1994 by the Australian postdoctoral fellow Marc Wilkins, a proteome includes all the proteins being expressed in a given cell at a given time. Wilkins called the study of the proteome, proteomics. According to Raj K. Puri, M.D., Ph.D., director of the Division of Cellular and Gene Therapies at the FDA’s Center for Biologics Evaluation and Research Proteomics, “Proteomics provides the opportunity for researchers to get a global view of the communications and always-changing events within a cell, instead of focusing on the more static singular gene.”

Researchers are learning that analyzing patterns of proteins, rather than identifying every active protein, may be sufficient for diagnosing disease. However, as the Duke researchers have found, a protein signature can also reveal how a person with Hepatitis C will respond to treatment.

There are many more stages of testing to go before hepatologists around the world use proteomics to screen patients for interferon-ribavirin therapy. However, this innovative application of a relatively new science is already getting people excited. Because of its potential to help physicians and their patients make better informed treatment decisions, testing patients for the non-responder protein signature might become routine when determining who is a candidate for interferon-ribavirin therapy.

References:

http://www.dukehealth.org/HealthLibrary/News/protein_signature_may
_predict_who_responds_to_hepatitis_c_treatment, Protein Signature May Predict Who Responds to Hepatitis C Treatment, Duke Medicine News and Communications, Retrieved November 2, 2008, Duke University Health System, November 1, 2008.

http://www.expasy.ch/proteomics_def.html, What is Proteomics?, Retrieved November 2, 2008, ExPASy, 2008.

http://www.fda.gov/fdac/features/2005/605_proteomics.html, Proteomics: Moving Beyond the Human Genome, Raymond Formanek Jr., Retrieved November 2, 2008, FDA Consumer Magazine, November/December 2005.

http://www.wisegeek.com/what-is-proteomics.htm, What is Proteomics?, J.S. Petersen, Retrieved November 2, 2008, WiseGeek, 2008.

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November 12, 2008

Antivirals Combined Without Interferon: New Trial

Three companies unite to begin an innovative Hepatitis C trial, where two oral antiviral drugs will be combined in the absence of interferon.

Pharmasset Announces Initiation of Hepatitis Antiviral Combination Study

Tuesday, 11 November 2008

Pharmasset, a clinical-stage pharmaceutical company, Roche and InterMune, a biotechnology company, have announced that the first patients have been dosed in an innovative clinical trial in patients chronically infected with the hepatitis C virus.

The trial is said to be the first to investigate the combination of two oral antiviral molecules in the absence of interferon. The initial study will evaluate the safety and combined antiviral activity of R7227 (ITMN-191), a protease inhibitor, and R7128, a polymerase inhibitor, in 14 days of combination therapy in treatment-naive patients infected with hepatitis C virus (HCV) genotype 1.

This direct antiviral combination study represents an important first step in evaluating the therapeutic potential of an all-oral, interferon-free combination treatment for HCV, the three companies said.

Dan Welch, chairman, CEO and president of InterMune, said: "The goal is to develop a treatment regimen that is better tolerated, shorter in duration and delivers higher sustained viral response rates. We are pleased to participate in the first clinical exploration of an all-oral, direct antiviral regimen towards that goal."

Source: Datamonitor

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HCV May Be Able to Be Cleared from Both Blood and Liver

Viral clearance doubled in a Hepatitis C Phase II trial during standard therapy when coupled with GlobeImmune's GI-5005. Because Hepatitis C must be eradicated not just from the blood, but also the liver, GI-5005's ability to speed the clearance rate of infected cells from the liver shows great therapeutic promise.

GlobeImmune Hepatitis C Therapeutic Vaccine, GI-5005, Doubles Viral Clearance and Increases RVR Rates in Phase 2 Clinical Trial

Four-Week Data Comparing GI-5005 Plus Standard of Care vs. Standard of Care to Be Presented Next Week in Late-Breaking Poster at AASLD Meeting; AASLD President Will Highlight Data at President's Press Conference

LOUISVILLE, CO, Nov 01, 2008 (MARKET WIRE via COMTEX) -- Four-week Phase 2 clinical trial data show that GI-5005, GlobeImmune's hepatitis C virus (HCV) targeted molecular immunogen (Tarmogen(R)), doubled viral clearance overall and in all major subgroups and doubled the rapid virologic response (RVR) rate in naive patients with high viral load. The study compared GI-5005 plus standard of care (SOC) -- pegylated-interferon plus ribavirin -- versus SOC alone in patients with chronic genotype 1 hepatitis C infection.

The study data will be presented by principal investigator John G. McHutchison, M.D., of Duke University, in a late-breaking poster next week at the 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). Treatment-naive patients with high viral loads at baseline ( > 600,000 IU/mL) saw a 2.6-fold improvement in RVR, which is defined as undetectable HCV RNA levels ( < 25 IU/ml) by four weeks. Treatment-naive patients with a high viral load at baseline are particularly difficult to treat to an RVR. RVR is highly predictive of whether a patient will achieve a sustained virologic response (SVR), or "cure," which is defined as undetectable HCV RNA at six months post-treatment. A significant improvement was also noted in the rate of viral reduction in the peripheral blood using viral kinetic analysis in all patients, with a 2-fold improved slope (0.32 log10/month difference, p=0.02) for patients receiving GI-5005 in addition to SOC. Comparable magnitude of increased viral clearance in GI-5005 treated patients was noted in all patient subgroups including prior non-responders and patients with high viral load at baseline.

"These data represent early but important evidence that a patient's natural immune response can be harnessed to positively influence important virologic endpoints with the potential to impact the course of chronic HCV infection," said Dr. McHutchison. "The rational combination of novel immune approaches such as GI-5005 with IFN-based standard of care or with novel direct acting antiviral agents holds promise in terms of ultimately improving clinical outcomes, shortening the exposure to toxic therapies, or both."

David Apelian, M.D., Ph.D., GlobeImmune Chief Medical Officer, said, "These data indicate that GI-5005 can increase the rate of clearance of infected cells from the liver, something that interferon-based therapies and antivirals are not designed to do. Direct acting antivirals act primarily by inhibiting viral replication, an important step, but they have not been shown to speed the immune clearance of infected cells from the liver. Ultimately, to achieve sustained virologic response, HCV must be eradicated not just from the blood, but also the liver. GI-5005 may improve this critical part of the treatment and healing process in a way that is complementary to standard of care and the new direct acting antivirals."

An HCV-targeted cellular immune response is essential to curing a patient with hepatitis C. Twenty percent of patients infected with hepatitis C have immune responses strong enough to clear the virus on their own, without medical intervention. However, for the remaining 80 percent who go on to develop chronic infection, it takes the immune system six to twelve months to eliminate the infection, even with SOC and the best antivirals. Improving the rate of viral clearance may ultimately lead to a decrease in the time needed for therapy.

"The role of the immune response in combating hepatitis C infection is often overlooked," added Apelian. "Most of the recent development interest has been focused on new direct-acting antivirals, which inhibit viral replication. However, to improve the rate of viral clearance from the liver, it is necessary to stimulate an HCV targeted cellular immune response. We believe that the Phase 2 data to date demonstrate the potential of GI-5005 to be an important and complementary part of the treatment of hepatitis C."

The GI-5005-02 clinical trial is a randomized, multi-center, Phase 2 study evaluating 140 patients, all with genotype 1 HCV infection. In the trial, 74 percent of the patients had never received prior treatment, and the remaining 26 percent experienced prior treatment failures.

GlobeImmune's GI-5005 is a targeted molecular immunogen (Tarmogen(R)) designed to elicit an HCV-specific T-cell response. Tarmogens are whole, heat-killed recombinant S. cerevisiae yeast that express antigens from one or more disease-related proteins.

About GlobeImmune
GlobeImmune Inc. is a private company developing targeted molecular immunogens, Tarmogens(R), for the treatment of cancer and infectious diseases. The company's lead product candidate, GI-5005, is a Tarmogen for the treatment of chronic hepatitis C infection (HCV). GI-5005 is designed to complement both the current standard of care and emerging novel therapies for HCV. The company's lead oncology program, GI-4000, targets mutated versions of the Ras oncoprotein for the treatment of pancreas cancer as well as other cancers that contain mutated Ras, including non-small cell lung cancer and colorectal cancer.

For additional information, please visit the company's Web site at www.globeimmune.com.

This news release and the anticipated presentation contain forward-looking statements that involve risks and uncertainties, including statements relating to initiation and progress of the Company's clinical trial programs and the preliminary results from the clinical trials. Actual results could differ materially from those projected and the Company cautions readers not to place undue reliance on the forward-looking statements contained in the release and anticipated presentation.
SOURCE: GlobeImmune, Inc.

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http://www.marketwatch.com/news/story/GlobeImmune-Hepatitis-C-
Therapeutic-Vaccine/story.aspx?guid=%7BC1318CCF-B9C7-47D1-B258-
3323DEBDB5C1%7D

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November 03, 2008

Vertex Treatment May Also Help Non-Responders

Here's some news to be announced at next week's meeting of the American Association for the Study of Liver Diseases. Vertex Pharmaceuticals will release mid-stage study results indicating the effectiveness of its experimental drug, telaprevir. This recent study, known as Prove 3, focused on 453 patients who had failed previous treatment with pegylated-interferon and ribavirin. The exciting news is that 52 percent of them saw the virus fall to undetectable levels for a 12-week period following treatment. In this article you'll learn how telaprevir might shorten treatment time by half, whether reducing dosage frequency could affect its safety, and how sustained viral response rate is determined.

Impressive Vertex hepatitis C drug data unveiled

By Bill Berkrot

NEW YORK, Nov 1 (Reuters) - A closely watched hepatitis C treatment being developed by Vertex Pharmaceuticals Inc showed an impressive ability to knock out the virus in patients who failed other treatments and those not previously treated for the serious liver disease, data from mid-stage studies show.

As it has in earlier studies, the experimental Vertex drug, telaprevir, when combined with standard treatments, showed the potential to cut in half the 48 weeks of treatment needed with the current standard of care and with greater efficacy.

In a study known as Prove 3 with 453 patients who had failed previous treatment with pegylated-interferon and ribavirin, 52 percent of those who received telaprevir saw the virus fall to undetectable levels and remain there 12 weeks after stopping treatment, according to interim analysis of data to be presented at the American Association for the Study of Liver Diseases meeting in San Francisco next week.

The percentage with undetectable virus 24 weeks after stopping treatment will yield the critical measure known as sustained viral response (SVR).

Within the 52 percent result, the virus was undetectable in 41 percent of patients who had not responded to previous treatment and 73 percent of those who had relapsed after previous treatment.

The Prove 3 result "is noteworthy as patients who have failed therapy are very difficult to manage due to limited available treatment options and are at greater risk for developing progressive liver disease," Dr. John McHutchinson, lead investigator of the Vertex-sponsored study, said in a statement.

Hepatitis C is a blood-borne liver disease that can lead to chronic liver disease, liver cancer, cirrhosis and death. The virus affects an estimated 3.2 million people in the United States alone and some 170 million worldwide.

Vertex also released final results from an earlier study called Prove 2 involving 323 hepatitis C patients who had not received prior treatment for the virus.

A higher SVR rate is expected in that patient population and telaprevir delivered on that.

In that study, 69 percent of patients in the telaprevir combination group had the virus fall to undetectable levels following 24 weeks of treatment, compared with a 46 percent SVR rate after 48 weeks of standard treatment.

A third study tested whether telaprevir might be as effective when given twice a day rather than three times per day as it has been in clinical trials.

The twice daily dosing, which could prove to be a more attractive option for patients, demonstrated similar efficacy and turned up no additional safety concerns, according to interim results, the company said.

The most common adverse side effects seen with telaprevir patients in the Prove studies were gastrointestinal problems, skin rash and anemia. Fourteen percent of telaprevir patients discontinued treatment due to adverse events in Prove 2 and 16 percent in Prove 3, Vertex said. That compared with 4 percent and 7 percent dropout rates in the control arms.

Vertex is set to begin pivotal late stage trials of telaprevir along with partner Johnson & Johnson.

Several companies are developing potential rival medicines, including boceprevir from Schering-Plough Corp, but telaprevir is widely expected to be the first in its class to reach the market.

(Reporting by Bill Berkrot, editing by Richard Chang)

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URL for Article Source:
http://www.reuters.com/article/rbssHealthcareNews/idUSN30269810
20081101

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October 27, 2008

Safer Than Liver Biopsy: A Simple Breath Test for HCV

A specially designed breath test has been found to be a safe and accurate alternative to liver biopsy for determining the degree of inflammation and fibrosis in patients with chronic Hepatitis C infection and normal ALT, according to researchers from Jerusalem.

(13)C-methacetin Breath Test for Non-invasive Assessment of Liver Fibrosis in Chronic Hepatitis C Patients

By Liz Highleyman

Over years or decades, chronic hepatitis C virus (HCV) infection can progress to advanced liver disease including severe fibrosis, cirrhosis, and hepatocellular carcinoma.

Liver biopsy remains the "gold standard" for assessing liver disease progression, but since the procedure is expensive, uncomfortable, and carries a small risk of complications, researchers have explored various non-invasive methods.

Several of these methods employ various blood biomarkers. Liver function tests that measure alanine aminotransferase (ALT) and aspartate aminotransferase (AST) indicate liver inflammation and may be a sign of progressive liver damage, but as many as one-third of hepatitis C patients with significant liver disease have persistently normal ALT.

As background, the authors noted that the test reflects hepatic microsomal function and has been shown to correlate with liver fibrosis. Such tests work on the principle that a damaged liver is unable to efficiently metabolize various substances, which can be measured in the expelled breath.

The investigators tested 100 patients with untreated chronic HCV infection along with 100 healthy HCV negative age- and sex-matched volunteers. The (13)C-methacetin breath test was administered following ingestion of 75 mg methacetin. All participants had undergone a liver biopsy within 12 months of receiving the breath test.

Patients with a necroinflammatory grade <4 (based on Ishak score) were defined as having low-level inflammation, while those with a grade > 4 were defined as having high-level inflammation. Individuals with a histological activity fibrosis stage < 2 were defined as having non-significant fibrosis, while those > 2 were defined as having significant fibrosis.

Results

• A proprietary algorithm used to differentiate liver inflammation in chronic hepatitis C patients with normal ALT achieved an area under the curve (AUC) of 0.90.

• Setting a threshold on the point of best agreement, at 83%, resulted in 82% sensitivity and 84% specificity.

• Applying another proprietary algorithm to differentiate patients with non-significant or significant fibrosis, 67% of liver biopsies could have been avoided by using the breath test.

• This algorithm achieved an AUC of 0.92, with a sensitivity of 91% and a specificity of 88%.

" There was no correlation between body mass index and breath test scores for patients with the same histological score.

"The continuous BreathID (13)C-methacetin breath test is an accurate tool for measuring the degree of inflammation and fibrosis in patients with chronic HCV infection and normal ALT," the study authors concluded. "As such, it may prove to be a powerful, noninvasive alternative to liver biopsy in the management of this patient population."

10/24/08

Reference
G Lalazar, O Pappo, T Hershcovici, and others. A continuous (13)C methacetin breath test for noninvasive assessment of intrahepatic inflammation and fibrosis in patients with chronic HCV infection and normal ALT. Journal of Viral Hepatitis 15(10): 716-728. October 2008.

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http://www.hivandhepatitis.com/hep_c/news/2008/102408_a.html

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October 07, 2008

How Fatty Acid Metabolism May Stop the Hepatitis C Virus

On September 28, 2008, researchers announced study results showing a new way to reduce viral replication (the progression of viral infection). The liver disease Hepatitis C may be chosen as a candidate for further exploration in this new technique to inhibit viral replication. For their study, the scientists had experimented with the herpes virus and fatty acid metabolism, and believe they can use existing drugs to inhibit viral replication in a number of diseases, including Hepatitis C. To learn why scientists are considering Hepatitis C as one of the candidates for further exploration of this unique way of metabolically blocking viral replication, read this article.

Existing Anti-obesity Drugs May Be Effective Against Flu, Hepatitis And HIV

ScienceDaily (Sep. 29, 2008) — Viruses dramatically increase cellular metabolism, and existing anti-obesity drugs may represent a new way to block these metabolic changes and inhibit viral infection, according to a study just published in the journal Nature Biotechnology.

Metabolism refers to all the reactions by which living things break down nutrients to produce energy, along with those by which they rebuild broken-down nutrients into complex molecules (e.g. DNA). A significant example is the breakdown of blood sugar (e.g. glucose) and its conversation via chain reactions into adenosine triphosphate, the energy-storing currency of cellular life. As an important offshoot of that process, glucose can also be converted into fatty acids, the lipid building blocks of human hormones and cell membranes. Many viruses, including influenza, HIV and hepatitis, use those same fatty acids to build instead their viral envelopes, outer coatings that help them penetrate human cells. Going into the study, little was known about the mechanisms through which viruses hijack metabolic building blocks from their cellular hosts, with older techniques providing a limited picture.

In the current study, a team of researchers from the University of Rochester Medical Center and Princeton University created a new technique to clarify these mechanisms, and found that the technique could identify anti-viral therapeutic targets. Researchers combined drug discovery technologies to capture for the first time the exact concentrations and turnover, in other words, the fluxes, of interchangeable molecules within the metabolic chain reactions that convert sugars into fatty acids. The fields of metabolomics and fluxomics have emerged to measure these patterns, and to provide insight into diseases with a metabolic component, from diabetes to infectious diseases to cancer.

"Using new fluxomic techniques, our study reveals that viral infection takes control of cellular metabolism and drives, among other things, marked increases in fatty acid synthesis," said Joshua Munger, Ph.D., assistant professor of Biochemistry and Biophysics at the University of Rochester Medical Center, and a study author. "We also found that if you target these increases in fatty acid metabolism using existing anti-obesity and anti-metabolism drugs, you inhibit viral replication."

A Thousand-fold Reduction in Viral Replication

In their experiments, Munger and colleagues developed a technique to measure changes in metabolic flux in human cells as they become infected by human cytomegalovirus (HCMV), an enveloped virus of the b-herpes family that infects most human adults and that causes severe disease in those with weakened immune systems. Researchers chose cytomegalovirus for experiments because it serves as an excellent model for processes at play in many enveloped viral infections and in cancers. HCMV replicates in a variety of human cell types, including fibroblasts, the cell type used in the study.

To study metabolic flux, Munger and his team created a stable, isotope-labeled version of glucose, which when "fed" to cells, was metabolized in a similar fashion as unlabeled glucose. Liquid chromatography and mass spectrometry were then employed to track the isotope label as it spread, or permeated, through the metabolic network. The impact of viral infection on cellular metabolism could be measured by the speed at which the labeled version spread, and then compared to uninfected cells. Given the complexity of interconnections within the metabolic network, the team also developed a novel computer model of metabolic function to analyze the data and guide further experimentation.

Many metabolic processes are essential to the survival of human cells, and so are not candidates for research efforts that would shut them down in the attempt to stop viral replication. For that reason, Munger and colleagues chose to look at whether interfering with glucose-to-fatty acid metabolism could stop viral replication, because fatty acid biosynthesis is not essential in adult humans. It does appear, however, to be essential to the ability of viruses to build their envelopes, reproduce and spread.

Thus, the team next used drugs known to inhibit enzymes that build fatty acids, acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), used in the treatment of obesity and high cholesterol, to determine whether HCMV-induced fatty acid production was necessary for enveloped viruses to make copies of themselves. Indeed, treatment (10 mg ml-1) with 5-tetradecyloxy-2-furoic acid (TOFA), an ACC inhibitor, resulted in a more than thousand-fold reduction in HCMV replication. C75 (trans-4-carboxy-5-octyl-3-methylene-butyrolactone), an inhibitor of FAS, resulted in a more than 100-fold effect at the same dose.

To investigate whether this requirement extended to other enveloped viruses, the team measured influenza A replication in the presence of the same TOFA and FAS inhibitors, and found similar reductions in replication. Influenza A has little in common with HCMV except for its lipid envelope.

Extensive clinical testing would be needed to draw conclusions about the safety of TOFA and C75, or similar compounds, as antiviral treatment. That said, the team took an early look at toxicity, exposing uninfected fibroblasts to C75 or TOFA for 96 hours. They found that the drugs blocked HCMV replication without causing cell toxicity or self-destruction (apoptosis).

Along with Munger, Jessica McArdle of the Department of Biochemistry and Biophysics contributed to the work. Bryson Bennett also worked on the project from the Lewis-Sigler Institute for Integrative Genomics in the Carl Icahn Laboratory at Princeton University. Leading the effort from the Princeton side was the corresponding author, Joshua Rabinowitz, who worked with Anuraag Parikh, Thomas Shenk in the Department of Molecular Biology, and Xiao-Jiang Feng and Herschel Rabitz at the Frick Laboratory. The work was supported by the National Institutes of Health (NIH) Metabolomics Roadmap initiative, the National Science Foundation, the Beckman Foundation, the American Heart Association, the National Science Foundation and the American Cancer Society.

"Recent studies have shown that fatty acid biosynthesis is important for the replication of diverse enveloped viruses," Munger said. "The replication of both hepatitis C and HIV, for example, has been linked recently with lipid synthesis, reinforcing our approach and its importance. Lastly, viral infection also clearly upregulates glycolysis, a marker for tumor growth, which is just the latest in the longstanding connection between viruses and cancer. Hopefully, our work will at some point provide insight into the metabolic manipulations seen in cancer as well."

Adapted from materials provided by University of Rochester Medical Center, via EurekAlert!, a service of AAAS.

URL for Article Source:
http://www.sciencedaily.com/releases/2008/09/080928145603.htm

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September 26, 2008

Medical Device Boasts Encouraging Data for Hepatitis C Treatment

A medical device designed to clear viruses and immunosuppressive proteins from the blood reduced Hepatitis C viral load for several people on dialysis. Further case studies will determine if the Aethlon Hemopurifier® can induce a rapid virological response against Hepatitis C.

Aethlon Medical Reports Promising Treatment Results In Hepatitis-C Infected Patients

September 21, 2008

Aethlon Medical, Inc. (OTCBB:AEMD) announced preliminary data of Hepatitis-C (HCV) infected patients treated with the Aethlon Hemopurifier®, a medical device designed to assist the immune response in combating infectious disease. The HCV treated patients were among end-stage renal disease (kidney dialysis) patients enrolled in human safety studies being conducted at the Fortis Hospital, in Delhi, India.

In the studies, robust viral load reductions were observed in tested patients completing a three-treatment Hemopurifier® protocol. The resulting data documented that two of three HCV patients tested responded with measurable viral load reductions during the course of three 4-hour Hemopurifier® treatments. The three treatments were administered during scheduled dialysis therapy every other day over the span of five days. The third patient showed both increases and decreases in viral load during the course of treatment, but demonstrated an overall reduction in follow-on viral load tests. Given the small sample size, viral load data was averaged for all 3 patients. Average initial HCV viral load was 3.13 x 108 viral units per ml of blood. After completion of three Hemopurifier® treatments, viral load was reduced an average 57% (final 4.1x107 IU/ml). The stepwise drop in HCV viral load averaged 36% per treatment. Follow-on testing indicated that HCV viral load was 60% lower than initial viral load values when measured three days after final Hemopurifier® treatment, and at seven days post treatment, viral load declined to 82% below starting viral load values. Additionally, none of the patients were being treated with antiviral drug therapy. Viral load measurements were performed with real-time quantitative polymerase chain reaction (RT-PCR). Control samples were measured in duplicate while treatment samples were generally measured in triplicate. In conclusion, the Hemopurifier® treatment of HCV infected patients undergoing dialysis resulted in a net viral load reduction of 60 to 80% with the effects of treatment progressing at least 7 days beyond Hemopurifier® treatment.

"The observation of progressive viral load reduction after only three Hemopurifier® treatments suggests that extended Hemopurifier® treatment applications could effectively inhibit disease progression in HCV patients," stated Aethlon Chairman and CEO, James A. Joyce. "We now plan to further demonstrate a rapid virological response (RVR) through a case study of an HCV patient receiving up to four weeks of Hemopurifier® therapy." Studies have shown that rapid virological response (RVR) at week four is a strong predictor of sustained virological response (SVR) in HCV patients. SVR is defined as undetectable viral load for a minimum period of five months after completion of treatment.

The opportunity for new antiviral strategies to fight HCV is significant, as approximately 180 million people worldwide (3% of the world's population) are HCV infected. According to the World Health Organization (WHO), only 30-50% of infected patients beneficially respond to the 48-week pegylated interferon-ribavirin treatment standard.

The Hemopurifier® is a first-in-class medical device designed to assist the immune response in combating infectious disease by rapidly clearing viruses and immunosuppressive proteins from circulation. The device provides a novel mechanism to complement antiviral therapies by suppressing the emergence of viral strains that cause drug resistance. The Hemopurifier® is also positioned to fill the unmet clinical need of treating patients resistant to drug therapy or infected by viral pathogens that are untreatable with drug and vaccine therapy. In HCV care, the device is positioned as an adjunct to improve clinical outcomes of the pegylated interferon-ribavirin treatment standard. Other opportunities in HCV care include the treatment of individuals who fail or are unable to endure standard of care therapy, end-stage renal patients infected with HCV, and HIV patients co-infected with HCV.

About Aethlon Medical

Aethlon Medical is the developer of the Hemopurifier®, a first-in-class medical device designed to treat infectious disease. The Hemopurifier® provides real-time therapeutic filtration of infectious viruses and immunosuppressive particles, and is positioned to address the treatment of drug and vaccine resistant viruses. Additionally, the device holds promise in cancer care, as research studies have verified the Hemopurifier® is able to capture immunosuppressive particles secreted by tumors. The Hemopurifier® is designed to act both as a stand-alone therapeutic, and as an adjunct treatment to enhance clinical benefit of established therapies. Pre-clinical studies conducted by researchers representing leading government and non-government health organizations both in the United States and abroad have documented the effectiveness of the Hemopurifier® in capturing from circulation the viruses that constitute pandemic threats, including H5N1 Avian Influenza (bird flu), and Dengue Hemorrhagic Fever (DHF) from circulation. The company is conducting studies to support the use of the Hemopurifier® as a broad-spectrum treatment countermeasure against bioterror threats, including Smallpox, and Ebola, Marburg, and Lassa hemorrhagic fever. Regulatory and commercialization initiatives in the United States are presently focused on bioterror threats, while international initiatives are directed toward naturally evolving pandemic threats, and chronic infectious disease conditions including the Human Immunodeficiency Virus (HIV) and Hepatitis-C (HCV). Aethlon demonstrated the safety of the Hemopurifier® in a 24-treatment human study at the Apollo Hospital in Delhi, India, and is currently conducting further human studies at the Fortis Hospital, also located in Delhi. The company has submitted an investigational device exemption (IDE) to the U.S. Food and Drug Administration (FDA) to advance the Hemopurifier® as a broad-spectrum treatment countermeasure against category "A" bioterror threats. Additional information regarding Aethlon Medical and its Hemopurifier® technology is available online at http://www.aethlonmedical.com.

Certain of the statements herein may be forward-looking and involve risks and uncertainties. Such forward-looking statements involve assumptions, known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of Aethlon Medical, Inc to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. Such potential risks and uncertainties include, without limitation, the Company's ability to raise capital when needed, the Company's ability to complete the development of its planned products, the ability of the Company to obtain FDA and other regulatory approvals permitting the sale of its products, the Company's ability to manufacture its products and provide its services, the impact of government regulations, patent protection on the Company's proprietary technology, product liability exposure, uncertainty of market acceptance, competition, technological change, and other risk factors. In such instances, actual results could differ materially as a result of a variety of factors, including the risks associated with the effect of changing economic conditions and other risk factors detailed in the Company's Securities and Exchange Commission filings.

Aethlon Medical, Inc.

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Hepatitis C Study Increases Interest in SCV-07

Trial results show SciClone's SCV-07 effectively reduces Hepatitis C viral load in previous non-responders with genotype 1. Based on these encouraging results, a follow-up study to evaluate SCV-07's potential to replace or improve the current Hepatitis C standard treatment will unfold next year.

UPDATE 2-SciClone hepatitis C drug shows promise in trial

Mon Sep 22, 2008
By Esha Dey

Sept 22 (Reuters) - SciClone Pharmaceuticals Inc (SCLN.O: Quote, Profile, Research, Stock Buzz) said its drug candidate for the treatment of chronic hepatitis C virus (HCV) showed antiviral activity in a mid-stage trial for patients who had relapsed after responding to prior treatments. The drug, SCV-07, was tested in a trial that evaluated its effect on hepatitis C viral load, a measure of the severity of a viral infection, and other measures of immune response.

The trial enrolled 34 patients who were infected with the difficult-to-treat genotype 1 strain of HCV and had previously responded to treatment but subsequently relapsed. SCV-07 demonstrated antiviral activity in some treated patients in the higher dosage groups, and the decrease in viral load in these patients was accompanied by an increase in an immunological biomarker usually associated with response against HCV.

"SciClone plans to investigate further SCV-07's potential to prime the human immune system against HCV and plans to discuss with regulators the initiation of a follow-up Phase II-B trial," Chief Executive Friedhelm Blobel said in a statement.

BWS Financial analyst Hamed Khorsand said the company could start the follow-up study in 2009.

"A partner for SCV-07 could be found now that there is some Phase II data under the drug's belt. However, we think SciClone would move forward with a Phase II-B trial before seeking a partner," Khorsand added. He has a "buy" rating on the stock.

SciClone said the follow-up trial could be used to determine whether SCV-07 is capable of replacing or improving the response to the current standard-of-care treatment. A combination of an enhanced form of interferon and ribavirin is currently the standard therapy for chronic hepatitis C.

Susquehanna Financial Group analyst Jason Kolbert said it's too early for a partnership as the company needs more data on SCV-07. The analyst has a "neutral" rating on the stock.

SciClone shares, which have shed 38 percent of their value since the start of the year, were trading flat at $1.27 in midday trade on Nasdaq. They touched a high of $1.38 earlier. (Editing by Anthony Kurian, Himani Sarkar;)

URL Source for Article:
http://www.reuters.com/article/rbssHealthcareNews/idUSBNG15855320080922

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September 22, 2008

New Hope for HCV

Funded by Pfizer, Tacere's licensed RNAi technology could change the way Hepatitis C is treated. A mechanism that inhibits genes from transferring information and creating new genetic material, RNAi-based drugs may be able to silence the genes that cause disease.

New life for hepatitis C treatment

Friday, September 12, 2008 | Modified: Tuesday, September 16, 2008

Sara Hall and Mike Catelani have come a long way since Tacere Therapeutics Inc.’s early days, sitting at Starbucks formulating their company.

The two executives rescued a potential treatment for the hepatitis C virus from their former company when it shut down U.S. operations in 2006.

Today, they are benefiting from an agreement with Pfizer Inc. that could take the company to new heights.

Tacere — based in a 1,500-square-foot space in the San Jose BioCenter incubator — has contracts worth $205 million if it meets upcoming milestones.

“If we didn’t start Tacere, (the treatment) basically would have died,” said Catelani, president and chief financial officer. “You get to take a shot like that, and there’s a chance you can make a difference in people’s lives.”

“We definitely bet right,” said Hall, chief executive officer.

Tacere’s treatment is based on RNAi, a mechanism that inhibits genes from transferring information and creating new RNA. Scientists believe that RNAi, which occurs naturally within cells, can be used to silence genes that cause disease.

“The underlying mechanism of RNAi is validated,” said Piper Jaffray senior research analyst Edward Tenthoff. “The therapeutic effect, the drug ability, has some proof of concept, but there are no RNAi drugs approved.”

Tacere’s first-in-class drug, TT-033, is a multitargeted approach focused on the hepatitis C virus, or HCV. TT-033 contains three separate RNAi molecules designed to shut down replication of all strains of the virus. Hall describes this approach as a “cocktail” in one drug.

The blood-borne infectious disease, caused by HCV, affects the liver and is spread by blood-to-blood contact. There is currently no vaccine to prevent the hepatitis C infection.

With only one drug approved to treat it, Hall said patients who contract the disease basically feel like they have the flu for a year. Symptoms can be medically managed, but only about 50 percent of patients can be cleared of the virus through medicines.

An estimated 200 million people worldwide are infected with the chronic condition, Catelani said, representing a $3.5 billion annual market.

Prior to founding Tacere, Hall was the CEO of Benitec Ltd., an Australian company developing RNAi-based therapeutics. Catelani was the company’s CFO. Hall joined Benitec through its acquisition of Sunnyvale-based Avocel Inc., also involved in RNAi. Ultimately, Benitec shut down its U.S. operations, and Tacere’s founders were eventually able to exclusively license the technology.

“We believed the hepatitis C program was of significant value, and we felt if we had a better corporate structure, we could do something with it,” Hall said.

Having unsuccessfully sought venture-capital backing, Tacere was contacted by Pfizer. Tacere entered into a collaboration and license agreement with Pfizer in January for the HCV compound and could receive potential payments of more than $145 million, along with future royalties on sales of the compound. Pfizer is also providing Tacere with funding to complete the necessary studies, as part of the initial phase of collaboration. The collaboration is focused on completing all necessary studies for submission of an investigational new drug application, as well as clinical development and commercialization.

Dr. Curt Scribner, senior vice president of clinical and regulatory affairs with RRD International LLC, is working as a consultant with Tacere. He said it’s one of the best small company-large company collaborations because it combines Tacere’s expertise with Pfizer’s funding to develop TT-033.

“They can only take it so far without a huge infusion of money,” said John Rossi, chairman and professor of the division of molecular biology at City of Hope, a biomedical research center near Los Angeles. “Pfizer has the capacity to make this a real treatment.”

The agreement with Pfizer is for worldwide rights, excluding Asia. Tacere’s initial investment came in June 2007 when it struck a deal with Tokyo’s Oncolys BioPharma to co-develop a treatment for hepatitis C in Asia. In March 2008, the two companies entered into a $60 million deal that will allow Oncolys to acquire Asian rights to TT-033.

With plenty of cash on hand, Catelani said Tacere isn’t seeking funding in the near future.

The company is in the midst of animal toxicology safety studies and later this month will move into studies involving nonhuman primates. It hopes to treat humans before the year’s end.

“If the safety data continues on the same lines, we feel confident in doing a Phase 1,” Hall said.

She added that if Tacere hits the next milestone, it will be capitalized for six years. In the meantime, Catelani said the company is also looking into other products to start developing in its pipeline.

“There are a number of technologies that have the potential to revolutionize medicine — if it works,” said another Tacere co-founder Amit Kumar, a previous venture capitalist and current CEO of biotech company Combi Matrix Corp.

Tacere faces competition in the industry from companies such as Alnylam Pharmaceuticals Inc. and Sirna Therapeutics, which was acquired by Merck & Co. for $1.1 billion in cash, Tenthoff said. However, the analyst said he wasn’t aware of other companies working on RNAi for HCV. He said given the huge treatment opportunity, speed to market and effect are going to be widely important.

“Most people feel pretty comfortable with the mechanism of RNAi,” he said. “The magic, the challenge, the most important thing now is to turn those small interfering RNAs into drugs, and that ain’t easy, and that’s where we’re seeing a lot of money invested.”

At-a-glance
Tacere Therapeutics Inc.
Headquarters: San Jose
CEO: Sara Hall
Employees: 5-6
Year founded: 2006
Phone: 408.960.2205
Web site: www.tacerebio.com

Lisa Sibley can be reached at 408.299.1841 or lsibley@bizjournals.com.

URL for article source:
http://sanjose.bizjournals.com/sanjose/stories
/2008/09/15/focus1.html?b=1221451200^1698814&page=2

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September 05, 2008

HCV Genotype 1 Viral Loads Decline

A six-month follow-up to Intercell's Phase II trial of their Hepatitis C vaccine with a topical toll-like receptor agonist showed a significant reduction in viral load. While data from two weeks after the vaccination series showed promise, participants with Hepatitis C genotype 1 had viral loads that continued to decline six months after treatment.

Favourable Six Months Follow-Up Results From Intercell's Phase II Therapeutic Hepatitis C Program

- Long term follow up results from chronically infected Hepatitis C patients strongly confirm and exceed positive data obtained earlier in 2008 - Study is the first to show a statistically significant and long-term antiviral effect of therapeutic Hepatitis C vaccination - Data pave the way and strongly support move into a second generation vaccine formulated with Intercell's adjuvant IC31(R) acting through TLR activation

VIENNA, Austria, Sept 03, 2008 /PRNewswire via COMTEX/ -- Today, Intercell AG (ICLL) announced the six months follow up data of its exploratory clinical Phase II study targeting treatment-naive Hepatitis C genotype-1 patients. As previously reported in February 2008, in this trial the therapeutic Hepatitis C vaccine (IC41) comprising five synthetic T-cell peptides and Intercell's first-generation poly-Arginine adjuvant (IC30) disclosed a statistically significant reduction of viral load in the blood of chronically infected patients up to 2 weeks after the last vaccination. The current long term follow up results show that this reduction was significantly more pronounced at six months after the final vaccination.

In the open label controlled multicenter Phase II study 50 genotype-1 patients, naive to standard treatment were enrolled for receiving a treatment schedule consisting of 8 intra-dermal IC41 vaccinations in biweekly intervals with topical application of the Toll-like receptor (TLR) agonist imiquimod. The previous analysis of 46 patients at 2 weeks after the last vaccination with IC41 showed already a statistically significant (p=0.001) HCV RNA decline of 0.2 log. The present follow-up data from 33 patients at six months after end of IC41 vaccination revealed an even greater viral load decline of 0.46 log (p=0.001). Interestingly, the virus decline (0.6 log) at the six months time point was most pronounced in patients with high initial viral load (> 2 million copies/ml). A parallel study arm conducted in 21 treatment-naive patients where the imiquimod application was omitted, did not show a significant reduction of the viral load. Thus the results strongly support the notion that the future co-administration of a TLR adjuvant, like IC31(R), is pivotal for the therapeutic effect of the vaccine.

"Our study is the first report to show significant long-term viral load effects of therapeutic vaccination. In particular the increasing RNA decline up to 6 months after vaccination is extremely encouraging and finally suggests the formulation of our vaccine with IC31(R), a strong TLR agonist. Furthermore our vaccine in future trials may be combined with standard therapy or novel antivirals." states Alexander von Gabain, Chief Scientific Officer of Intercell.
Although options for the treatment of chronic Hepatitis C with Interferon/Ribavirin have improved, treatment will remain very difficult and a significant unmet medical need, especially in the case of Genotype 1. Novel immunotherapies, and possibly therapeutic vaccines, might become an option in the arena of existing and future HCV combination treatments. Thus, Intercell will follow its development strategy that will also take advantage of an enlarged antigen portfolio and of IC31(R), Intercell's second-generation adjuvant that has recently demonstrated the generation of T-cell responses, in human vaccine trials, to a level not yet seen for other known adjuvants.

About Hepatitis C
HCV is a major cause of chronic liver disease, including cirrhosis and liver cancer. According to the World Health Organization (WHO), approximately 170 million people worldwide are chronic HCV carriers (3% of the world's population), including about 10 million Europeans, 3.9 million Americans and 2 million Japanese. 35,000 new infections occur in the United States alone each year. The substantial unmet medical need is underscored by the fact that each year 8,000 to 10,000 deaths and 1,000 liver transplants in the United States are due to HCV.

Currently, there is no vaccine against Hepatitis C available, and the infection can only be treated with a combination of Interferon and Ribavirin -- a long-term therapy with limited efficacy and substantial side effects. It also gives rise to high treatment costs for patients. In 2002, worldwide sales of HCV drugs totalled around EUR 2.8bn, and demand has since grown significantly. The market has been seen to expand to about EUR 3.5bn by 2006.

About Intercell AG
Intercell AG is a growing biotechnology company that designs and develops novel vaccines for the prevention and treatment of infectious diseases with substantial unmet medical needs. The Company's technology platforms include an antigen-discovery system, two proprietary adjuvants and a novel patch-based delivery system. Based on these technologies, Intercell has strategic partnerships with a number of global pharmaceutical companies, including Novartis, Merck & Co., Inc., Wyeth, Sanofi Pasteur, Kirin and the Statens Serum Institut.

The Company's lead product is a vaccine against Japanese Encephalitis. That vaccine successfully concluded pivotal Phase III clinical trials in 2006, and Intercell is seeking marketing approval in the United States, Europe, Australia and Canada. Approval in those markets is anticipated during the second half of 2008.

The Company's development pipeline includes Phase II vaccine programs for Pseudomonas (in-house development) and S. aureus, which is being developed with Merck & Co. Inc. The Company's novel Travelers' Diarrhea vaccine patch will enter Phase III testing in 2009. Intercell is also in clinical trials of a vaccine enhancement patch with injected pandemic influenza vaccines (one shot plus patch). In addition, five other products focused on infectious diseases are in preclinical development.

Intercell is listed on the Vienna stock exchange under the symbol "ICLL".

For more information, please visit: http://www.intercell.com
This communication expressly or implicitly contains certain forward-looking statements concerning Intercell AG and its business. Such statements involve certain known and unknown risks, uncertainties and other factors which could cause the actual results, financial condition, performance or achievements of Intercell AG to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Intercell AG is providing this communication as of this date and does not undertake to update any forward-looking statements contained herein as a result of new information, future events or otherwise.
SOURCE Intercell AG

http://www.intercell.com

URL for article source: http://www.marketwatch.com/news/story/favourable-six-months-follow
-up-results/story.aspx?guid=%7B157839DE-3B3E-4FF4-AB69-EB9EE125BF57%
7D&dist=hppr

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Former Anti-Itch Drug Useful Against Hep C

California scientists have found that an old antihistamine drastically reduces Hepatitis C viral replication.

Old drug shows new use against hepatitis C

STANFORD, Calif., Sept. 2 (UPI) -- U.S. researchers say they've developed a novel approach to fighting the hepatitis C virus's reproduction process using an obsolete antihistamine.

The Stanford University Medical Center scientists said the advance involves two discoveries. "One is that a protein called NS4B is instrumental in binding some of the genetic material, or RNA, and allowing the hepatitis C virus to replicate," the researchers said. "The other is that the former anti-itching drug clemizole hydrochloride could hinder that protein, resulting in a tenfold decrease in virus replication with no apparent harm to infected liver-like cells."

Since the former antihistamine drug has previously been used by people, it is automatically eligible for human testing.

"We're excited about this and we're actively moving forward toward clinical trials," said Dr. Jeffrey Glenn, an associate professor of gastroenterology and hepatology and a senior co-author of the paper with Professor Stephen Quake. The lead authors are Dr. Shirit Einav and bioengineer Doron Gerber.

The research that also included doctoral student Paul Bryson, postdoctoral student Ella Sklan, research associate Menashe Elazar and Sebastian Maerkl, a former member of Quake's group, appears in the online edition of the journal Nature Biotechnology.

URL for article source: http://www.upi.com/Science_News/2008/09/02/Old_drug_shows_new_use
_against_hepatitis_C/UPI-92061220375093/

Posted by Editors at 10:52 AM --- Printer-friendly version

August 22, 2008

Advanced Trial Could Change Hepatitis C Treatment

Hundreds of non-responders to interferon-ribavirin combination therapy will be enrolled in a late stage clinical trial for Vertex's telaprevir.

Vertex to begin expanded trial for hepatitis drug

Tuesday, August 19, 2008
Boston Business Journal - by Mark Hollmer

Vertex Pharmaceuticals Inc. will begin a wide-scale late stage human clinical trial for its hepatitis C treatment.

The Cambridge, Mass. company (Nasdaq: VRTX) said on Tuesday that it had agreed with regulatory authorities in the U.S. and European Union to begin the trial for telaprevir in combination with another treatment. Scientists for this trial will focus on patients for whom a previous treatment hasn’t worked.

More than 650 patients will be enrolled at over 100 facilities in the U.S. and the European Union, and enrollment should be complete by the fiscal 2009 first quarter.

Getting a hepatitis C treatment to market would be an enormous achievement. About 6 million patients in the U.S. and European Union alone suffer from hepatitis C, Vertex estimates.

URL for article source:
http://milwaukee.bizjournals.com/boston/stories/2008/08/18/daily10.html

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August 12, 2008

Popular Blood Thinner May Reduce Liver Scarring for HCV Patients

Successful animal studies have paved the way for a human trial to determine if warfarin prevents liver damage in those with Hepatitis C.

Warfarin may prevent liver failure in hepatitis C patients

http://www.healthcarerepublic.com/news/PHARMACIST/836668/Warfarin-may
-prevent-liver-failure-hepatitis-C-patients/

05-Aug-08

Warfarin could be used to prevent liver failure in thousands of patients with hepatitis C, a new study suggests.

UK researchers found that warfarin significantly reduced the level of liver fibrosis in mice with chronic liver injury.

Digital image analysis of liver histology of wild-type mice treated with warfarin showed a 33 per cent reduction in mean fibrosis area compared with controls, according to the study published in the Journal of Thrombosis and Haemostasis.

The alpha-smooth muscle actin, which is a biochemical marker of fibrosis at a cellular level, was also reduced by 10 per cent in wild-type mice treated with warfarin.

It follows previous research by the same group which found that patients prone to blood clotting who have hepatitis C have accelerated liver scarring.

The researchers have now begun a two-year multi-centre trial, funded by the Medical Research Council (MRC), in 90 hepatitis C patients who have had liver transplants. These patients suffer rapid progression to fibrosis, and the follow-up trial should bring faster results, the researchers say.

Posted by Editors at 10:12 AM --- Printer-friendly version

August 05, 2008

R1626 Could Help Defeat Hepatitis C

Whether added to standard combination therapy or as a monotherapy, studies show that R1626 is a powerful HCV anti-viral medicine.

New treatment therapy helps inhibit hepatitis C

Public release date: 31-Jul-2008
http://www.eurekalert.org/pub_releases/2008-07/w-ntt073108.php

Two new studies examine the use of the nucleoside polymerase inhibitor, R1626, to the standard therapy for hepatitis C. The reports appear in the August issue of Hepatology, a journal published by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases (AASLD). The articles are available online at Wiley Interscience (www.interscience.wiley.com).

The first study shows that adding the treatment to standard therapy with pegylated interpheron alpha plus ribavirin leads to a synergistic antiviral effect. In the search for new and better treatments, researchers have been testing R1626, which previously has been used to inhibit HCV replication in vitro.

The study group included 104 patients with HCV genotype 1. Twenty-one took 1500 mg of R1626 twice a day along with peginterferon alpha-2a. Thirty-two took 3000 mg of R1626 twice a day along with peginterferon alpha-2a. Thirty-one took 1500 mg of R1626 twice a day along with peginterferon alpha-2a and ribavirin. And 20 took the standard of care treatment of peginterferon alpha-2a with ribavirin.

After four weeks, HCV RNA was undetectable in 29 percent, 69 percent, and 74 percent of patients in the respective study arms, compared to 5 percent of patients receiving the standard of care treatment.

"The results of the present study show a marked increase in antiviral effect in patients when ribavirin is added to the combination of R1626 and peginterferon alfa-2a," the authors report.

In conclusion, the authors report, "this phase 2a study has demonstrated a potent reduction in HCV RNA by R1626 and high viral responses with up to 74 percent rapid viral response after 4 weeks of treatment. The strong antiviral effect between R1626, peginterferon alfa-2a and ribavirin, suggests that the dose of one or both of these agents could be lowered to improve tolerability without significantly compromising efficacy."

A second study shows that, in patients with chronic hepatitis C, the antiviral activity increased with the dosage. Side effects were tolerable and there was no evidence of viral resistance.

For 14 days, the patients were treated with R1626 orally at twice-daily doses of either 500 mg, 1500 mg, 3000 mg, 4500 mg, or placebo. "The decreases in HCV RNA from baseline observed with R1626 indicates potent antiviral activity and lack of viral load rebound in the significant majority of patients following 14 days of monotherapy," the authors report. Current therapy for patients with chronic hepatitis C virus (HCV) requires up to 48 weeks of treatment.

In addition, the study showed that R1626 was well tolerated up to 3000 mg and there was no evidence of viral resistance in this study, perhaps reflecting the potency of R1626 as an anti-viral agent.

###

Article: "R1626 plus peginterferon alfa-2a provides potent suppression of HCV RNA and significant antiviral synergy in combination with ribavirin." Pockros, Paul; Nelson, David; Godofsky, Eliot; Rodriguez-Torres, Maribel; Everson, Gregory; Fried, Michael; Ghalib, Reem; Harrison, Stephen; Nyberg, Lisa; Shiffman, Mitchell; Hill, George; Najera, Isabel; Chan, Anna. Hepatology ; August 2008; 10.1002/hep22357.

Article: "Robust antiviral activity of R1626, a novel nucleoside analog: a randomized, placebo-controlled study in patients with chronic hepatitis C." Roberts, Stuart; Cooksley, Graham; Dore, Gregory J.; Robson, Richard; Shaw, David; Berns, Heather; Hill, George; Klump, Klauss; Najera, Isabel; Washington, Carla. Hepatology ; August 2008; 10.1002/hep22321.

For Media Inquiries Only:
Sean Wagner
swagner@wiley.com
781-388-8550
Wiley-Blackwell

Posted by Editors at 11:14 AM --- Printer-friendly version

July 09, 2008

Anadys' ANA773 Hepatitis C Phase I Trials in Netherlands

Reducing the dosing schedule in half, Anadys Pharmaceuticals continues its investigation of ANA773, a Toll-Like Receptor-7 agonist prodrug. Approaching the Hepatitis C virus differently from most other contenders, Phase I clinical trials evaluating the safety, tolerability and viral-load decline associated with ANA773 are about to begin in the Netherlands.

Anadys Pharmaceuticals Resumes Clinical Investigation of TLR7 Mechanism in HCV

http://money.cnn.com/news/newsfeeds/articles/prnewswire/200807071605PR_NEWS_USPR_____LAM070.htm

SAN DIEGO, July 7 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) announced today that it is resuming clinical investigation of the Toll-Like Receptor-7 (TLR7) mechanism for the treatment of chronic hepatitis C. Based on preclinical pharmacology testing and the results of completed 13-week GLP animal toxicology studies, Anadys has received clearance to initiate a clinical trial of ANA773, the Company’s oral TLR7 agonist prodrug, under a clinical trial application (CTA) in the Netherlands. Following initial dosing in healthy volunteers, this trial will explore every-other-day dosing over 28 days in HCV patients. Anadys also continues to enroll patients in a separate Phase I clinical trial of ANA773 in oncology that is ongoing under an IND in the United States.

"In an extensive preclinical program conducted with ANA773, we have previously shown that the profile of immune stimulation resulting from TLR7 activation can be dramatically modulated by altering the schedule of administration," said James Freddo, M.D., Anadys’ Chief Medical Officer. "Now, results of toxicology studies employing every-other-day dosing of ANA773 have shown that we can achieve desired levels of immune stimulation sustained over 13 weeks without adverse toxicology findings. The favorable toxicology profile seen to date, coupled with the stable induction of interferon-alpha dependent responses when ANA773 is dosed every other day over 13 weeks, have convinced us that ANA773 has the potential to demonstrate benefit in patients infected with HCV."

Steve Worland, Ph.D., Anadys’ President and CEO, commented, "The decision to take ANA773 into HCV, which will be our third clinical development program to commence dosing this year, reflects an expansion of Anadys’ development efforts in HCV. As an approach to treat hepatitis C, the TLR7 mechanism is independent from, and potentially complementary to, ANA598, Anadys’ non-nucleoside HCV polymerase inhibitor currently in Phase I clinical development." Commenting on the expected impact this expansion will have on the Company’s cash outlook for 2008, Dr. Worland added, "Because the ANA773 hepatitis C program is highly leveraged off our oncology program, we expect to carry forward all three clinical development programs this year within our previous 2008 cash utilization projection of $29 to $31 million."

ANA773 Phase I Clinical Trial in HCV

The Phase I clinical trial of ANA773 in HCV will be conducted under a two-part protocol. Part A of the study will include both single and multiple doses of ANA773 in healthy volunteers. Successive cohorts of volunteers will receive ascending dose levels of ANA773. The primary objectives of Part A of the study are to assess safety and tolerability. In Part B of the study, HCV patients will receive ANA773 every other day for 28 days. The primary objectives of Part B are to assess safety, tolerability and viral load decline. The starting dose level in HCV patients will be selected based on safety, tolerability and immune responses seen in healthy volunteers in Part A. It is expected that this study design will allow initial dosing in HCV patients at a dose that will have demonstrated a desired magnitude of immune stimulation in the healthy subjects, and that dosing in patients will initiate prior to completion of dose escalation in Part A of the study. Approximately 40 healthy volunteers and 24 patients are anticipated to be enrolled in this study. Dosing is expected to begin in healthy volunteers within the next few weeks and in HCV patients early in the fourth quarter of 2008.

About ANA773 and TLR Pharmacology

ANA773 is an orally administered prodrug of a novel TLR7-specific agonist. Results from pre-clinical pharmacology studies have shown that ANA773 can elicit desired immune responses and that the profile of response can be modulated by both dose and schedule of administration. Results of recently completed 13-week GLP toxicology studies have shown that with every-other-day dosing of ANA773, immune stimulation of a magnitude believed to confer therapeutic potential can be achieved without adverse toxicology findings. The immune stimulation observed with every-other-day dosing of ANA773 in monkeys included induction of interferon-alpha and interferon dependent responses at levels that are sustained over 13 weeks of dosing.

The recently obtained results with every-other-day dosing of ANA773 over 13 weeks contrast with results from prior 13-week animal toxicology studies that utilized daily dosing of ANA975, a TLR7 agonist prodrug previously in development by the Company for the treatment of chronic hepatitis C. In initial 13-week animal toxicology studies of ANA975 dosed daily, unexpected findings associated with intense immune stimulation were observed. When lower daily doses of ANA975 were then explored in a subsequent 13-week animal toxicology study, it was determined that adverse findings were present even at dose levels where desired immunostimulatory effects were not measurable, following which the decision was made in 2007 to discontinue development of ANA975.

Webcast of Conference Call

Anadys will host a conference call today, July 7, 2008 at 2:00 p.m. Pacific Daylight Time to discuss Anadys’ plans to resume clinical investigation of the TLR7 mechanism in HCV. A live webcast of the call will be available online at http://www.anadyspharma.com. A telephone replay will also be available approximately one hour after completion of the call. To access the telephone replay, dial 888-286-8010 (domestic) or 617-801-6888 (international), passcode 84526379. The webcast and telephone replay will be available through July 21, 2008.

About Anadys

Anadys Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company dedicated to improving patient care by developing novel medicines in the areas of hepatitis C and oncology. For the treatment of chronic hepatitis C, the Company is developing ANA598, a non-nucleoside polymerase inhibitor, and ANA773, an oral TLR7 agonist prodrug. The Company is also developing ANA773 for the treatment of cancer.

Safe Harbor Statement

Statements in this press release that are not strictly historical in nature constitute "forward-looking statements". Such statements include, but are not limited to, references to (i) the expected timing and planned development activities for ANA773, including the timing for commencing dosing in the planned ANA773 HCV clinical trial; (ii) the belief that ANA773 has the potential to demonstrate benefit in patients infected with HCV; (iii) the belief that the TLR7 mechanism will potentially be complementary to ANA598; (iv) expectations regarding Anadys’ cash utilization for 2008; (v) the planned study design of the two-part protocol of the ANA773 clinical trial in HCV; (vi) Anadys’ expectation to begin dosing HCV-infected patients with ANA773 prior to the completion of the healthy volunteer portion of the study at a dose that will have demonstrated a desired magnitude of immune stimulation in the healthy subjects; and (vii) the belief that ANA773 can elicit immune stimulation of a magnitude sufficient to confer therapeutic potential without adverse safety issues. Such forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause Anadys’ actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. For example, the results of preclinical studies, including the toxicology studies described in this press release, may not be predictive of future results, and Anadys cannot provide any assurances that ANA773 or ANA598 will not have unforeseen safety issues in future toxicology studies, will have favorable results in future clinical trials or will receive regulatory approval. In addition, Anadys’ results may be affected by risks related to competition from other biotechnology and pharmaceutical companies, its effectiveness at managing its financial resources, its ability to successfully develop and market products, difficulties or delays in its preclinical studies or clinical trials, difficulties or delays in manufacturing its clinical trials materials, the scope and validity of patent protection for its products, regulatory developments involving future products and its ability to obtain additional funding to support its operations. Risk factors that may cause actual results to differ are more fully discussed in Anadys’ SEC filings, including Anadys’ Form 10-K for the year ended December 31, 2007 and Anadys’ Form 10-Q for the quarter ended March 31, 2008. All forward-looking statements are qualified in their entirety by this cautionary statement. Anadys is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.

SOURCE Anadys Pharmaceuticals, Inc.

Posted by Editors at 03:23 PM --- Printer-friendly version

June 27, 2008

Good News for Non-Responders to HCV Combination Therapy

A Phase 3 trial evaluating ZADAXIN® (thymalfasin) as a potential third component for Hepatitis C traditional combination therapy has just been completed. Although the data is currently being analyzed and won't be available until later in the year, the lead investigator anticipates good news for previous non-responders.

SciClone and Sigma-Tau Provide Update on Phase 3 Hepatitis C Study

June 26, 2008
http://money.cnn.com/news/newsfeeds/articles/marketwire/0410557.htm

SciClone Pharmaceuticals, Inc. (NASDAQ: SCLN) and Sigma-Tau S.p.A. today announced that all 553 enrolled patients successfully completed a Phase 3 trial. After 48 weeks of therapy, all patients responding to treatment have now completed their 24-week follow-up. The unblinded data from the trial are expected to be available in the fourth quarter of 2008. The Phase 3 trial is evaluating ZADAXIN® (thymalfasin) in combination with pegylated interferon alpha and ribavirin as a treatment for patients with hepatitis C virus (HCV) who have not responded to prior therapy with pegylated interferon alpha and ribavirin. In February 2008, SciClone and Sigma-Tau S.p.A. announced promising blinded interim data from this trial.

"The completion of the study is an important step toward unblinding the data. Previously reported data from this Phase 3 hepatitis C trial have been promising," said Mario Rizzetto, M.D., Professor of Gastroenterology, San Giovanni Battista Hospital, University of Torino, Italy, and lead investigator of the trial. "The standard data review and analysis is underway with an unblinding of the data expected in late 2008."

"We continue to believe that thymalfasin could represent an important advance in the treatment of non-responder hepatitis C patients and address a growing and acute need," said Friedhelm Blobel, Ph.D., President and Chief Executive Officer of SciClone Pharmaceuticals, Inc.

The treatment approach for HCV using a combination of thymalfasin together with pegylated interferon plus ribavirin is patent protected by SciClone in most major markets including the United States and Europe until 2021. Details of the thymalfasin triple therapy for HCV, the hepatitis C virus, and thymalfasin may be found in the press release from SciClone Pharmaceuticals dated February 11, 2008, at www.sciclone.com.

About SciClone

SciClone Pharmaceuticals is a biopharmaceutical company engaged in the development of therapeutics to treat life-threatening diseases. SciClone's lead product ZADAXIN® is currently being evaluated in a late-stage clinical trial for the treatment of hepatitis C, and successfully completed a phase 2 clinical trial in malignant melanoma. ZADAXIN is approved for sale in select markets internationally, most notably in China where SciClone has an established sales and marketing operation. A key part of SciClone's strategy is to leverage its advantage and broaden its portfolio in the rapidly growing Chinese market by in-licensing or acquiring the marketing rights to other products, such as DC Bead(TM). For the U.S. market, SciClone's other clinical-stage drug development candidates are RP101 for the treatment of pancreatic cancer and SCV-07 for the treatment of hepatitis C. For more information about SciClone, visit www.sciclone.com.

About sigma-tau Group

Sigma-tau Group is a leading research-based Italian pharmaceutical company with a consolidated 2007 turnover of approximately EUR 665 million (US$ 920 million) and over 2500 employees worldwide. The therapeutic areas in which sigma-tau Group focuses its Research and Development include cardiovascular disease, metabolism, neurology, oncology and immunology, totalling 48 projects. Over 30 indications are explored in clinical trials with 24 molecules of which 17 are proprietary and the majority of them (14) are NCEs. Sigma-tau Group has operating subsidiaries throughout Europe and the U.S. and is active in every major pharmaceutical market. For additional information about sigma-tau Group, please visit www.sigma-tau.it.

The information in this press release contains forward-looking statements including our expectations and beliefs regarding future sales and financial results for 2008, and progress, timing and results of our clinical trials. Words such as "expects," "plans," "believe," "may," "will," "anticipated," "intended" and variations of these words or similar expressions are intended to identify forward-looking statements. In addition, statements that refer to expectations, goals, projections or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. These statements are not guarantees of future performance and are subject to risks, uncertainties and assumptions that are difficult to predict. Therefore, our actual results could differ materially and adversely from those expressed in any forward-looking statements as a result of various factors, including changes in demand for ZADAXIN, the progress or failure of clinical trials, our actual experience in executing on our objectives, the performance of our partners, maintenance of the sufficiency and eligibility of the enrolled patient population, unanticipated delays or additional expenses incurred during our clinical trials, our future cash requirements, delays in analyzing and synthesizing data obtained from clinical trials, the performance and future actions of our strategic partners, unexpected delays in clinical trial enrollment, future actions by the U.S. Food and Drug Administration or equivalent regulatory authorities in Europe and the fact that experimental data and clinical results derived from studies with a limited group of patients may not be predictive of the results of larger studies, as well as other risks and uncertainties described in SciClone's filings with the Securities and Exchange Commission. Further, although our financial guidance is based on our current estimates, factors such as the actual timeline and design of the phase 3 melanoma clinical trial and final decisions regarding expense sharing arrangements for the trial could alter the estimates of our research and development expenses, net loss and year-end cash balance for 2008.

Corporate Contact:
Ana Kapor
SciClone Pharmaceuticals, Inc.
650.358.3437

Posted by Editors at 10:35 AM --- Printer-friendly version

June 23, 2008

Purer, Less Costly Interferon for Hepatitis C and B Treatment

The Taiwan-based biopharmaceutical company PharmaEssentia Corp. is testing P1101, its third-generation PEG-interferon-alpha drug candidate. Because it is a longer-lasting, purer interferon that is less costly to produce, P1101 could enhance the treatment options for Hepatitis C and B.

(Taiwan) PharmaEssentia announces milestone in development of new third-generation interferon hepatitis B and C drug candidate

www.biotecheast.com

(Press release, PharmaEssentia Corp.)

18 June, 2008

Drug development company PharmaEssentia Corp. today announced that new PK/PD data on P1101, its third-generation PEG-interferon-alpha drug candidate for hepatitis B and C, showed the drug is particularly long-lasting compared to the two other pegylated-interferon drugs currently on the market. This indicates that PharmaEssentia's drug may only need to be injected once every two or more weeks by the patient, compared to the usual once-a-week administration.

Reducing dosage frequency is considered desirable for minimizing side effects and increasing the efficacy; and is more convenient for the patient as such biopharmaceutical drugs must usually be administered by injection.

Additionally, the modified structure of PharmaEssentia's PEG-INF-alpha makes for a purer drug, leading to a simpler manufacturing process and better quality control over the end product, particularly when produced at higher doses. P1101 has only a predominant single positional isomer connecting the PEG molecule on the protein, compared with 8 to 14 isomers found in the two other pegylated-interferon drugs, respectively.

Less frequent dosage should also mean a lower end cost and better compliance for the patient.

Assuming that upcoming clinical trails are all completed successfully, Dr. KC Lin, founder and CEO of PharmaEssentia, sees the drug gaining rapid acceptance and market share upon launch.

"Our drug will be purer, easier to manufacture, and more importantly, a more convenient and cheaper interferon option for doctors and patients. It's set to transform the whole picture of HCV/HBV treatment," explained Lin.

Summary of pharmacokinetics (PK) and pharmacodyamics (PD) studies:
PK results: Mean serum concentrations of PEG-IFN after a single subcutaneous dose of 30ug/kg of one of the two other pegylated-interferon drugs currently on the market, or P1101 (PharmaEssentia) were measured. PEG-IFN was detectable in all four animals through 14 days after P1101 administration, while PEG-IFN was only detectable in two out of four monkeys for the 14 days duration after administration of the two other pegylated-interferon drugs.

PD results: A single subcutaneous dose of 30 ug/kg of one of the two other pegylated-interferon drugs currently on the market, or P1101, resulted in significant increase in serum 2’,5’-OAS (biomarker of IFN-alpha exposure) concentration. Serum 2’,5’-OAS concentration reached its Cmax 72 hours after dosing and gradually declined for the animals treated with the other two pegylated-interferon drugs. For animals receiving the P1101 dose, serum 2’,5’-OAS concentration also reached Cmax 72 hours after dosing. However, 2’,5’-OAS concentration only decreased slightly throughout the 14 days of the study period.

About PharmaEssentia Corp.:
PharmaEssentia Corp., a Taiwan-based biopharmaceutical company, is focusing its efforts on making improvements to the biologics family of drugs using a combination of its own proprietary novel site-specific PEGylation, a medicinal chemistry approach, and protein engineering technologies to create new "PEGylated" biologics.

Through its novel technology platform, PharmaEssentia Corp. has a series of PEGylated biologics called the "PEG-5 biologics": PEG-IFN-alpha-2b, IFN-beta, GCSF, EPO, GH, undergoing various stages of research and development. The current market for the diseases targeted by these drugs is estimated at around US$25 billion with an annual growth rate of 9 percent.

PharmaEssentia’s PEG-IFN-alpha-2b a third-generation long-acting interferon for the treatment of hepatitis B and C, is currently in preparation for US FDA IND filing in the 3rd quarter of 2008. PEG-IFN-alpha-2b has only a single form compared to 14 and 8 with the two other pegylated-interferon drugs currently on the market, thus requiring a potentially less frequent administration regime. Through a unique refolding process, PEG-IFN-alpha-2b has a better yield (up to as high as 40 percent compared to wild type INF) and longer half-life (administration every two weeks or more) at a competitive CMC (Chemical Manufacturing Control).

PharmaEssentia at BIO 2008, San Diego:
We are currently seeking qualified co-development or out-licensing partners for our PEG-Interferon-alpha drug candidate (HBV, HCV). Please contact us to arrange a meeting during the partnering sessions at BIO 2008, 17-18 June, in San Diego, or feel free to visit us at booth 2501 at the Taiwan Pavilion.

PharmaEssentia CEO Dr. KC Lin will also be giving a presentation at the BIO 2008, Business Forum, Room 5B, 3:00pm, 18 June, 2008. You are very welcome to attend.

Contact:
PharmaEssentia Corp.
13F, No. 3 YuanQu St., Nankang District
Taipei 115, Taiwan
Tel: 886 2 2655 7688
Fax: 886 2 2655 7626
www.pharmaessentia.com

Ms. Shu-Fen Li, MBA
Director of Business Development and Strategic Planning
Ph: +886-2-2655-7688 ext. 7812
shufen_li@pharmaessentia.com

For editors:
PEG-IFN-alpha-2b = PEG-IFN-α-2b
IFN-beta = IFNβ

Posted by Editors at 02:35 PM --- Printer-friendly version

New Technology May Help Treat Hepatitis

While pharmaceutical companies are racing to find safer, more effective treatments for viral Hepatitis C and B, physicists from Arizona have a unique perspective on accomplishing the same goal. Learn how these scientists believe the virus could be rendered harmless with this non-traditional, non-invasive procedure.

by Nicole Cutler, L.Ac.

As one of the leading causes of liver disease, both the Hepatitis B and C viruses remain difficult to eliminate. Although medical technology has produced some potent medicines to battle these liver-invading viruses, they are ineffective for a significant percentage of those infected. However, scientists from Arizona have stepped into an entirely new field of medicine that proposes a completely different approach to dismantling a virus. By mathematically determining the frequency by which viruses can be shaken to death, physics may trump the biological sciences in the quest to safely eliminate viral pathogens.

Although this innovative technology’s potential for fighting Hepatitis B or C is currently in a conceptual stage, the logic behind it is intriguing and hopeful. All objects have resonant frequencies at which they naturally vibrate; however, too much vibration can destroy an object. A good example of this phenomenon is the destruction of the Tacoma Narrows Bridge, which warped and finally collapsed in 1940 due to a wind that rocked the bridge back and forth at one of its resonant frequencies. Similar to how opera singers can hit notes that shatter glass, recent experimental evidence has shown that laser pulses tuned to the right frequency can kill certain viruses.

An idea that runs parallel to the marvel of resonant frequency is a breakthrough explained by Bruce Lipton in his book, The Biology of Belief. In this archetype, Lipton believes that the key to life does not lie within a person’s DNA – but, rather, within the mechanisms of the cell membrane. In contrast to conventional medical science, proponents of Lipton’s work advocate that the cell’s membrane operates in response to its environment and controls how the genes inside the cell are interpreted.

In Lipton’s biological model, the cell dies when the membrane is destroyed, just as a person would die if their brain were removed. Applying this theory to the work of physicist Otto Sankey of Arizona State University, using resonant frequencies that stress the outer shell of the virus to its breaking point would theoretically kill the virus residing inside. According to Sankey, “The capsid of a virus is something like the shell of a turtle. If the shell can be compromised [by mechanical vibrations], the virus can be inactivated.”
Consisting of small units of protein, the capsid is the outer shell of a virus. The three primary purposes of a capsid include:

1. protecting the virus’s genetic material
2. detecting cells suitable for infection
3. initiating infection by “opening” the target cell to inject DNA into the cytoplasm

As a result of Sankey’s initial discovery, researchers are hard at work developing methods to calculate the vibrational motion of every atom of a capsid. Armed with knowing the vibrational motion of a capsid’s atoms, the lowest resonant frequencies can be determined. Even though determining any particular capsid’s lowest resonant frequency may be within arms reach, this technology is still a long way from being used to neutralize viruses in infected people.
One of the biggest challenges of using lasers to break open a capsid is that a laser’s light cannot penetrate the skin very deeply. However, Sankey suggests that there may be ways to circumvent this limitation such as:

· Hooking a person up to a dialysis-like machine that cycles blood through a tube where it can be zapped with a laser.

· Due to its penetrative ability, applying a resonant frequency with ultrasound equipment instead of a laser.

Adding to the task of using lasers to kill a hepatitis virus is the apparent complexity of the Hepatitis B and Hepatitis C capsids.

Hepatitis B Capsid – As published in the June 2006 edition of the journal Molecular Cell, Scripps researchers examined the capsid of the Hepatitis B virus. According to Professor Mark Yeager, MD, PhD, the Hepatitis B virus is enormous, nearly 10 times larger than a hemoglobin molecule. The Hepatitis B capsid has icosahedral symmetry, resembling the geometric structure of a geodesic dome. The capsid itself is contained within an outer envelope formed by a lipid bilayer, similar to the membranes that enclose all human cells. The membrane of the Hepatitis B virus is studded with glycoprotein spikes, which bind to receptors on liver cells to mediate infection.

Hepatitis C Capsid – The Hepatitis C capsid also has the twenty-sided icosahedral crystalline form. This structure forms an efficient sphere that can be built from the smallest building blocks, conserving host cell energy for the production of viruses. Additionally, Hepatitis C also surrounds their capsids with an additional envelope of lipids to further insulate the virus from damage.

Once the frequency is established for dismantling a viral capsid, and a safe and effective way to administer that frequency is determined, then the hepatitis viruses will no longer be a threat to liver health. The Arizona scientists assure us that normal cells will not be affected by virus-killing lasers or sound waves because they have resonant frequencies much lower than those of viruses. Another promising characteristic of this technology is that viruses are unlikely to develop a resistance to mechanical shaking like they do with drugs.

Applying vibrational physics to therapeutic virology is a fascinating concept. With enough time, experimentation and successful trials, scientists are hopeful they will find the right resonant frequencies for each virus. Although this technology has a long way to go, a zap of light could change the way we treat viral hepatitis in the future.

References:

Dryden, Kelly A, Mark Yeager et al., Native Hepatitis B virions and capsids Visualized by Electron Cryomicroscopy, Molecular Cell, June 2006.

Lipton, Bruce, PhD, The Biology of Belief: Unleashing the Power of Consciousness, Matter and Miracles, Mountain of Love/Elite Books, Santa Rosa, CA, 2005.

www.epidemic.org, Anatomy of the Virus, Trustees of Dartmouth College, 2008.

www.iscid.org, Capsid, International Society for Complexity, Information and Design, 2008.

www.livescience.com, New Way to Kill Viruses: Shake them to Death, Michael Schirber, Imaginova Corp., February 2008.

www.mercola.com, A New Way to Kill Viruses: Shake them to Death, Dr. Joseph Mercola, 2008.

www.sciencedaily.com, Researchers Map Infectious Hepatitis B Virus, ScienceDaily LLC, 2008.

Posted by Editors at 02:12 PM --- Printer-friendly version

June 10, 2008

HCV Viral Load Reduced in Phase I/II Trial

Given to those already infected with Hepatitis C, ChronVac-C® is designed to boost the immune response against the virus. Preliminary trial results report a decrease in viral load of over 95 percent in the first patient to complete ChronVac-C® therapy.

Reduced Hepatitis C Viral Level Achieved with DNA Vaccine Delivered by Inovio Biomedical's Electroporation Delivery System in Phase I/II Clinical Study

June 4, 2008
www.businesswire.com

SAN DIEGO--(BUSINESS WIRE)--Inovio Biomedical Corporation (AMEX:INO), a leader in enabling the development of DNA vaccines using electroporation-based DNA delivery, announced today that its partner, Tripep AB, reported preliminary results indicating a dramatic reduction in hepatitis C viral load in its ongoing phase I/II clinical study of its ChronVac-C® therapeutic DNA vaccine, which is delivered using Inovio’s electroporation-based DNA delivery system. This result is from the first patient in the middle dose group to complete treatment against hepatitis C virus infection. Samples taken before, during and after treatment show that the viral levels in blood successively decreased by more than 95% during treatment. Inovio's electroporation delivery technology is intended to enhance the potency of DNA vaccines against cancers and infectious diseases.

ChronVac-C® is a therapeutic vaccine given to individuals already infected with the hepatitis C virus with the aim to clear the infection by boosting the immune response against the virus. This clinical study is being conducted at the Infectious Disease Clinic and Center for Gastroenterology at the Karolinska University Hospital in Huddinge and Solna, respectively, in Sweden. The intended enrollment of 12 patients will be divided into three dose groups with increasing doses of ChronVac-C(R). Each patient receives four vaccinations one month apart. After the last vaccination, patients are followed for another six months. The study's main purpose is to assess safety. It is also testing whether the treatment boosts the immune response to HCV (immunogenicity) and its effect on virus replication in the liver. If the patient is completely virus-free six months after completing treatment, he/she will be considered cured.

In the lowest dose group, two patients who completed treatment developed a T-cell response to hepatitis C. The preliminary result from this first patient to complete treatment in the intermediate dose group is the first to indicate a significant reduction in viral load. There have been no severe adverse events.

“The benefit we would hope to see from a successful hepatitis C virus DNA vaccine would be a dramatic reduction in viral levels,” stated Avtar Dhillon, MD, Inovio's president and CEO. “We look forward to seeing the longer term results of this DNA vaccine and its potential to address this multi-billion dollar market.”

About Inovio Biomedical Corporation

Inovio Biomedical (AMEX:INO) is focused on developing multiple DNA-based immunotherapies and DNA vaccines. Inovio is a leader in developing human applications of electroporation using brief, controlled electrical pulses to increase cellular uptake of a useful biopharmaceutical. Human data has shown that Inovio’s electroporation-based DNA delivery technology can significantly increase gene expression and immune responses from DNA vaccines. Immunotherapy partners include Merck, Wyeth, Vical, University of Southampton, Moffitt Cancer Center, the U.S. Army, National Cancer Institute, and International Aids Vaccine Initiative. Inovio’s technology is protected by an extensive patent portfolio covering in vivo electroporation. More information is available at www.inovio.com.

This press release contains certain forward-looking statements relating to our plans to develop our electroporation drug and gene delivery technology. Actual events or results may differ from our expectations as a result of a number of factors, including the uncertainties inherent in clinical trials and product development programs (including, but not limited to, the fact that clinical results referenced in this release may not be indicative of results achievable in other trials or for other indications and that results from one study may necessarily not be reflected or supported by the results of other similar studies), the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of Inovio’s technology as a delivery mechanism, the availability or potential availability of alternative therapies or treatments for the conditions targeted by Inovio or its collaborators, including alternatives that may be more efficacious or cost-effective than any therapy or treatment that Inovio and its collaborators hope to develop, evaluation of potential opportunities, issues involving patents and whether they or licenses to them will provide Inovio with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether Inovio can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of our technology by potential corporate or other partners or collaborators, capital market conditions, and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2007, our 10-Q for the three months ended March 31, 2008 and other regulatory filings from time to time. There can be no assurance that any product in our product pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proved accurate.

Contacts

Investors:
Inovio Biomedical Corporation
Bernie Hertel, 858-410-3101
or
Media:
Ronald Trahan Associates Inc.
Ron Trahan, 508-359-4005, x108

Posted by Editors at 02:24 PM --- Printer-friendly version

May 30, 2008

Optimism Swells After Liver Conference

Several researchers at the May 2008 Digestive Disease Week in San Diego reported encouraging progress in their mission to extinguish liver disease. One of the advancements announced includes monitoring dendritic cells to determine which Hepatitis C patients will fare well during treatment.

New Hope for Liver Diseases

By Kathleen Doheny
HealthDay Reporter
Friday, May 23, 2008; 12:00 AM

www.washingtonpost.com

FRIDAY, May 23 (HealthDay News) -- Human liver cells have been generated from embryonic stem cells using a new model, hopefully opening the door to help scientists screen for harmful side effects of new drugs before they are used in patients.

That was one of several reports on advances against liver diseases that were presented this week at Digestive Disease Week 2008 in San Diego.

Other presentations involved ways to predict which patients with hepatitis C might benefit from long-term antibiotic therapy and information about how monitoring the body's viral load in hepatitis B patients may help predict liver cancer.

Scientists from the University of Edinburgh, Scotland, reported they had efficiently generated human liver cells from embryonic stem cells without the problems that have plagued scientists in the past. The new model is unique, said Dr. David Hay, a senior fellow at the university's MRC Centre for Regenerative Medicine, who spoke at a press conference Tuesday.

His team developed a model that allows them to focus on key enzymes which are crucial in drug metabolism. Other clinical applications, he said, include the fact that the liver cells generated in vitro could be used in bioartificial devices, helping maintain normal function when the liver fails.

Down the road, said another investigator, Dr. Philip Newsome, the hope is that the cells could be used in liver transplantation.

The advance was praised by the press conference moderator, Dr. John M. Vierling, chief of hepatology at Baylor College of Medicine, in Houston.

The team produced "highly differentiated cells that maintain function," Vierling said, a feat that has thus far proved elusive to others working on the effort. "It is an extraordinarily rich advance to be exploited in many ways," he added.

Predicting which patients with chronic hepatitis C infection, another liver ailment, will respond to treatment may be done by monitoring the dendritic cells, the cells that are the most potent stimulator of the immune system's T-cells, said Dr. John Mengshol, a fellow in the department of gastroenterology and hepatology at the University of Colorado Health Sciences Center, in Denver.

Treatment for hepatitis C virus routinely involves 48 weeks of combination antiviral therapy. Side effects include flu-like symptoms, and treatment is successful in only half of patients.

So, predicting who will and won't respond would be helpful. Mengshol and his colleagues evaluated 64 patients with hepatitis C virus of the genotype 1, the most common strain and the most difficult to treat.

Researchers have found that therapy affects the dendritic cells differently. Mengshol's team studied blood samples from each patient before treatment and at 24 weeks after starting it. They looked at the population of two different types of dendritic cells, among other factors.

Levels of one type of dendrite cells normalized in those who responded to the treatment, while levels of those who did not respond did not.

Why some patients respond to therapy and others don't has been an ongoing mystery, Mengshol said. Monitoring the dendritic cells may help doctors determine who might respond to therapy.

In another study, Dr. Uchenna Iloeje, director of virology for Global Clinical Research at Bristol-Myers Squibb Co., reported that monitoring the viral load of hepatitis B virus in patients with that disease is a significant predictor of who will be likely to get liver cancer.

In the study, researchers followed more than 3,500 patients for 11.5 years, Iloeje said.

"Over time, those at highest risk of liver disease had a sustained hepatitis B load," he said.

The liver is the largest organ inside the body. It changes food into energy, cleans alcohol and poisons from the blood, and makes bile, a liquid that aids digestion.

More information

For more on liver diseases, go to Medline Plus.

SOURCES: John M. Vierling, M.D., professor, medicine and surgery, chief, hepatology, Baylor College of Medicine, Houston; John Mengshol, M.D., Ph.D., fellow, University of Colorado School of Medicine, Denver; Uchenna Iloeje, M.P.H, M.B.B.S., director, virology, Global Clinical Research, Bristol-Myers Squibb; May 20, 2008, presentations, Digestive Disease Week 2008, San Diego

Posted by Editors at 02:40 PM --- Printer-friendly version

May 01, 2008

Highly Effective Against HCV Genotype 1

When tested on people with Hepatitis C genotype 1, R7128 proved to be an effective addition to combination therapy after just four weeks' time. In addition to its anti-viral effect, polymerase inhibitor R7128 received good marks for safety and minimal side effects.

R7128 is Safe, Effective in Short-Term for Patients With Hepatitis C Virus Genotype 1: Presented at EASL

By Emma Hitt, PhD

www.docguide.com

MILAN, Italy -- April 29, 2008 -- R7128, a potent inhibitor of hepatitis C virus (HCV) polymerase, appears effective and well tolerated at week 4 after initiation of treatment in combination with pegylated interferon alfa-2a (PEG-INF)/ribavirin, according to interim findings of a randomised trial of patients with genotype 1 HCV, researchers reported here at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL).

John McHutchison, MD, Associate Director, Duke Clinical Research Institute, Durham, North Carolina, described how the study sought to evaluate the efficacy and safety of R7128 at a dose of 500 mg BID (n = 20) and 1500 mg BID (n = 20), compared with placebo (n = 10) at 4 weeks; each arm also received PEG-INF/ribavirin. Patient characteristics were similar among study arms.

R7128 demonstrated a dose-dependent effect on efficacy parameters. Patients in the placebo group had a 2 log10 reduction in HCV RNA, compared with a 3 log10 reduction of in the 500-mg BID arm and a 5 log10 reduction in the 1500-mg BID arm. Rapid viral response was achieved in 10%, 30%, and 95% of patients in the placebo arm, the 500-mg BID, and the 1500-mg BID R7128 arms, respectively. alanine aminotransferase normalisation was achieved in 60%, 80%, and 70% of the 3 arms, respectively.

R7128 was generally well tolerated, with no apparent serious adverse events associated with R7128. The most common mild adverse events with the 1500-mg BID dose included fatigue (40% vs 20% in placebo), chills (35% vs 20% in placebo), and headache (65% vs 40% in placebo). No evidence of additional haematologic adverse events with R7128 was noted. In addition, amylase, bilirubin, blood urea nitrogen, and creatinine measurements were comparable at week 4 among treatment arms, with no evidence of renal toxicity.

Dose reductions and discontinuations were similar among treatment arms. One patient receiving R7128 1500 mg BID discontinued all treatment due to anorexia, diarrhea, and weight loss on study day 24.

"We observed a significant antiviral effect of R7128 in combination with PEG-INF [plus ribavirin] at week 4," Dr. McHutchison concluded. "Approximately 85% of patients receiving R7128 achieved undetectable HCV RNA by week 4."

According to Dr. McHutchison, two additional cohorts will be enrolled in the current 4-week triple combination study: a 1000-mg BID arm in treatment-naive patients with genotype 1 HCV and a 1500-mg BID arm in treatment-experienced patients with genotype 2 or 3 HCV. Both arms will also receive PEG-INF/ribavirin. An international phase 2b study is also underway to evaluate R7128 in triple combination for up to 12 weeks.

Funding for this study was provided by Roche.

[Presentation title: Potent Antiviral Activity of the HCV Nucleoside Polymerase Inhibitor R7128 With PEG-IFN and Ribavirin: Interim Results of R7128 500mg BID for 28 Days. Abstract 66]

Posted by Editors at 02:01 PM --- Printer-friendly version

April 30, 2008

Investigational Drug Beats Standard Therapy in Hepatitis C Study

A Phase IIa trial investigating triple combination therapy with PEGASYS, COPEGUS and Roche's investigational drug R1626, demonstrated a higher response rate than traditional combination therapy alone. While R1626's effectiveness and high barrier to resistance makes it a top Hepatitis C contender, the following six months will determine if its ability to clear the virus lasts.

Roche's Investigational Hepatitis C Polymerase Inhibitor, R1626, Demonstrated Significant End-of-Treatment Response In Phase IIa Study

www.medicalnewstoday.com

Article Date: 27 Apr 2008

Roche's investigational therapy for chronic hepatitis C virus (HCV) infection, R1626, has shown a significant end-of-treatment response rate when given in combination with PEGASYS(R) (peginterferon alfa-2a) and COPEGUS(R) (ribavirin). R1626 also shows a high barrier to the development of resistance.

After four weeks of treatment with this triple combination, followed by 44 weeks of PEGASYS and COPEGUS, levels of HCV were undetectable in 84 percent of patients infected with genotype 1 virus. This was higher than patients treated with PEGASYS and COPEGUS alone for the entire 48-week treatment period (65 percent). These new data were presented in a late-breaker oral session at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL), being held in Milan, Italy.

R1626 was discovered and developed at Roche and belongs to a class of antivirals called polymerase inhibitors, which are being investigated with the current standard of care for hepatitis C combination therapy with pegylated interferon and ribavirin.

"These results demonstrate that R1626 holds significant promise to potentially increase the number of hepatitis C patients who can be successfully treated," said Dr. David Nelson, Director of Hepatology and Liver Transplantation at the University of Florida, Gainesville, Florida. "Since most patients responded very early in treatment with R1626, we expect sustained virological response (SVR) rates that improve significantly on those achieved with the current standard of care. I look forward to SVR data from this Phase IIa study, and to results of the ongoing Phase IIb study."

Patients in this Phase IIa study will be followed for an additional 24 weeks with no treatment to determine the SVR rate, which indicates successful treatment.

More About the Phase IIa Study and End-of-Treatment Results

The Phase IIa study is a multicenter trial that enrolled 104 patients with genotype 1 HCV, who had not previously received treatment. Its primary endpoint was to evaluate the four-week efficacy and safety of combining R1626 with PEGASYS alone or with PEGASYS plus COPEGUS, in comparison to a current HCV standard of care (SOC), pegylated interferon plus ribavirin.

Patients were randomized into the following treatment groups:

-- Group A: R1626 1,500 mg twice a day plus PEGASYS 180 mcg weekly for four weeks

-- Group B: R1626 3,000 mg twice a day plus PEGASYS 180 mcg weekly for four weeks

-- Group C: R1626 1,500 mg twice a day plus PEGASYS 180 mcg weekly plus COPEGUS 1,000/1,200 mg daily for four weeks

-- Group D (standard of care group): PEGASYS 180 mcg weekly plus COPEGUS 1,000/1,200 mg daily for four weeks

Following the four weeks of treatment in this study, all patients received PEGASYS 180 mcg weekly plus COPEGUS 1,000/1,200 mg daily for an additional 44 weeks to complete the 48-week trial.

The study found:

-- Data collected at four weeks showed that patients receiving the triple combination (Group C) had a mean decrease in viral load of 5.2 log10 from baseline, indicating a robust and rapid virological response.

-- At week 48, HCV was undetectable in 84 percent of patients (26 of 31) who received the triple combination of R1626 1,500 mg BID + PEGASYS + COPEGUS compared with 65 percent of patients (13 of 20) treated with the SOC.

-- A higher incidence of grade four neutropenia was reported in the R1626 treatment arms during the four-week treatment period; however, after stopping treatment with R1626, absolute neutrophil counts returned to the level typically seen with patients receiving the SOC alone.

R1626 - A High Barrier to the Development of Resistance

In a separate oral presentation at EASL, it was reported that R1626 continues to present a high barrier to the development of viral resistance. This is a serious concern emerging in the development of small molecule treatments for hepatitis C. Resistance to R1626 has not been yet been identified, after either two weeks of R1626 monotherapy, or after four weeks in patients treated with R1626 in combination therapy.

Rapid Development of R1626 - A Large Phase IIb Study is Now Fully Enrolled

A large Phase IIb study with R1626 was initiated in November 2007 to define the optimal dose of R1626, in combination with PEGASYS and COPEGUS. This Phase IIb trial, called POLI 1, is now fully enrolled with approximately 500 patients, all with genotype 1 hepatitis C.

About Hepatitis C

Hepatitis C is a blood-borne infectious disease of the liver and a leading cause of cirrhosis, liver cancer and the need for liver transplants. According to the Centers for Disease Control and Prevention (CDC), an estimated 4.1 million Americans (1.6 percent) have been infected with hepatitis C; 3.2 million are chronically infected. The number of new infections per year has declined from an average of 240,000 in the 1980s to about 26,000 in 2004. CDC estimates the number of hepatitis C-related deaths could increase to 38,000 annually by the year 2010, surpassing annual HIV/AIDS deaths.

About PEGASYS

PEGASYS, in combination with COPEGUS (ribavirin), are indicated for the treatment of adults with chronic hepatitis C who have compensated liver disease and have not previously been treated with interferon alpha. Efficacy has been demonstrated in patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A) and patients with HIV disease that are clinically stable (e.g., antiretroviral therapy not required or receiving stable antiretroviral therapy). In addition, PEGASYS in combination with COPEGUS is the first and only FDA-approved regimen for the treatment of chronic hepatitis C in patients coinfected with hepatitis C and HIV. PEGASYS is the only pegylated interferon indicated for the treatment of adult patients with chronic hepatitis B (HBeAg positive and HBeAg negative chronic hepatitis B who have compensated liver disease and evidence of viral replication and liver inflammation).

PEGASYS is dosed at 180mcg as a subcutaneous injection taken once a week. COPEGUS is available as a 200mg tablet, and is administered orally two times a day as a split dose. Roche has backed PEGASYS with the most extensive clinical research program ever undertaken in hepatitis C, with major studies initiated to advance treatment for hepatitis C patients with unmet needs, including patients co-infected with HIV and HCV, African Americans, patients with cirrhosis, and patients who have failed to respond to previous therapy.

IMPORTANT SAFETY INFORMATION

PEGASYS, alone or in combination with COPEGUS, is indicated for the treatment of adults with chronic hepatitis C virus infection who have compensated liver disease and have not been previously treated with interferon alpha. Patients in whom efficacy was demonstrated included patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A).

The most common adverse events reported for PEGASYS and COPEGUS combination therapy observed in clinical trials were fatigue/asthenia (65%), headache (43%), pyrexia (41%), myalgia (40%), irritability/anxiety/nervousness (33%), insomnia (30%), alopecia (28%), neutropenia (27%), nausea/vomiting (25%), rigors (25%), anorexia (24%), injection site reaction (23%), arthralgia (22%), depression (20%), pruritus (19%) and dermatitis (16%).

About Roche

Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. pharmaceuticals headquarters of the Roche Group, one of the world's leading research-oriented healthcare groups with core businesses in pharmaceuticals and diagnostics. For more than 100 years in the U.S., Roche has been committed to developing innovative products and services that address prevention, diagnosis and treatment of diseases, thus enhancing people's health and quality of life. An employer of choice, in 2007 Roche was named Top Company of the Year by Med Ad News, one of the Top 20 Employers (Science) and ranked the No. 1 Company to Sell For (Selling Power). In previous years, Roche has been named as a Top Company for Older Workers (AARP) and one of the Best Companies to Work For in America (Fortune). For additional information about the U.S. pharmaceuticals business, visit our website http://www.rocheusa.com. Product and treatment information for U.S. healthcare professionals is available at http://www.RocheExchange.com.

All trademarks used or mentioned in this release are protected by law.

Roche
http://www.rocheusa.com

Posted by Editors at 02:26 PM --- Printer-friendly version

April 29, 2008

Improves Outcome for Hep C Genotype 4

Currently approved for treating contagious diarrhea in children, nitazoxanide has been found to make pegylated interferon-based treatment for Hepatitis C genotype 4 more effective. Prompting new trials in the U.S. and Europe, this drug is now being evaluated for Hepatitis C genotype 1.

Nitazoxanide Demonstrates Activity in Treatment-Naive Patients With Hepatitis C Virus Genotype 4: Presented at EASL

By Emma Hitt, PhD

www.docguide.com

MILAN, Italy -- April 29, 2008 -- Nitazoxanide significantly improves response to pegylated interferon (PEG-IFN)-based therapy in patients with chronic hepatitis C virus genotype 4 (HCV-4), according to new research findings presented here at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL).

Jean-Francois Rossignol, MD, Research Scientist, and Cofounder, Romark Institute For Medical Research, Tampa, Florida, reported the results of a randomised trial of nitazoxanide, an oral agent that targets host-cell interactions with HCV. Dr. Rossignol and colleagues sought to evaluate the antiviral activity and safety of nitazoxanide in combination with PEG-IFN alfa-2a, with or without ribavirin.

A total of 120 patients with chronic HCV-4 were sequentially randomised to 1 of 3 treatment arms. The first arm was a standard-of-care arm: PEG-IFN alfa-2a plus ribavirin (RBV) for 48 weeks. The second arm was nitazoxanide for 12 weeks followed by nitazoxanide plus PEG-IFN alfa-2a for 36 weeks. The third arm was a triple therapy consisting of nitazoxanide for 12 weeks followed by nitazoxanide combined with PEG-IFN alfa-2a plus RBV for 36 weeks.

PEG-IFN alfa-2a was injected by clinical investigators at 180 mcg/kg/week while ribavirin was dosed at 1000 to 1200 mg/day. Nitazoxanide was administered at 500 mg twice daily with food.

Patients were previously untreated, with the exception of 12 interferon-experienced patients included in each of the nitazoxanide-containing arms.

During the monotherapy lead-in phase with nitazoxanide, a modest (0.25 log10) but statistically significant decrease in HCV ribonucleic acid (RNA) from baseline to week 12 was observed (P = .0032). Out of 76 patients, 5 had a drop in HCV RNA of greater than 1 log10 from baseline to week 12; and 1 patient had undetectable HCV RNA, with a 5.4 log10 decline in HCV RNA and normalised alanine aminotransferase (ALT) test results at week 12. There was no significant change in overall ALT measurements during the lead-in period.

Among the interferon-naive patients (n = 96), the patients receiving the triple regimen (nitazoxanide plus PEG-IFN plus RBV) achieved a higher sustained viral response (SVR) than the patients receiving the standard of care (79% vs 50%; P = .023). In the nitazoxanide arm without RBV, the SVR was 61%. The rapid viral response (RVR) was also higher in patients receiving the triple therapy compared with those receiving the standard of care (64% vs 38%; P = .048).

In the interferon-experienced patients (n = 24), no efficacy differences were observed between the 2 nitazoxanide-containing arms (not compared with standard of care).

"Adverse events in the overall population were characteristic of those typically observed with pegylated interferon and ribavirin, with no additional effects resulting from nitazoxanide," Dr. Rossignol noted here on April 25. "Additional clinical trials of nitazoxanide in interferon-naive patients and nonresponders to pegylated interferon plus ribavirin have been initiated in patients with HCV genotype 1 in the United States and Europe."

Nitazoxanide was initially developed as an antiprotozoal, antiviral, and antibacterial agent, and is approved for the treatment of diarrhoea caused by Cryptosporidium and Giardia in children. Nitazoxanide has since shown activity against HCV and hepatitis B virus.

[Presentation title: Randomized Controlled Trial of Nitazoxanide-Peginterferon-Ribavirin, Nitazoxanide-Peginterferon and Peginterferon-Ribavirin in the Treatment of Patients With Chronic Hepatitis C Genotype 4. Abstract 68]

Posted by Editors at 01:57 PM --- Printer-friendly version

April 18, 2008

News: Fluvastatin Lowers Cholesterol and Hepatitis C Viral Load

Researchers from Oklahoma have revealed that a drug commonly prescribed for high cholesterol also lowers Hepatitis C viral load. Although not capable of clearing Hepatitis C on its own, a Phase II trial will reveal its effectiveness in combination with interferon and ribavirin.

Researchers Find New Treatment for Hepatitis C

www.physorg.com

April 11, 2008

Researchers at the Oklahoma University Health Sciences Center have found a new use for an old drug. Their findings appear online in the American Journal of Gastroenterology.

The drug, Fluvastatin, has been approved since 1993 by the U.S. Food and Drug Administration for the treatment of elevated cholesterol in adults. Millions of patients have taken Fluvastatin for cholesterol without difficulty.

In a study of 31 veterans at the Veteran’s Administration Medical Center in Oklahoma City, researchers found that Fluvastatin significantly lowered the viral load, or levels of hepatitis C virus, for up to six weeks when used alone.

“This research is the first to demonstrate the antiviral activity of Fluvastatin in human beings infected with hepatitis C, most of whom were non-responders to the standard of care treatment,” said Ted Bader, M.D., the principle investigator on the project and director of liver diseases at the OU Health Sciences Center.

Since Fluvastatin will not completely clear the hepatitis C virus by itself, researchers have started a phase II randomized, controlled trial that combines Fluvastatin with the standard treatment of peg-interferon and ribavirin. They hope to use the combination of medicines to significantly improve the cure rate for hepatitis C. After further required testing and approval, the drug could be available as a new treatment for hepatitis C far sooner than any other anti-hepatitis C drug currently under research and development.

Posted by Editors at 10:20 AM --- Printer-friendly version

April 04, 2008

Hepatitis C Drug ITMN-191 Appears Safe

In addition to demonstrating a Hepatitis C anti-viral effect, an early trial investigating ITMN-191 met safety goals. With this good news, a Phase II study will evaluate this drug in combination with pegylated interferon and ribavirin.

InterMune Hepatitis C Drug Passes Study
© 2008 The Associated Press

April 1, 2008, 9:48AM

www.chron.com

BRISBANE, Calif. — Biotechnology company InterMune Inc. said Tuesday its hepatitis C drug candidate met safety goals in an early stage clinical trial and showed signs of effectiveness.

The drug candidate ITMN-191, being developed with Swiss drug company Roche, reduced hepatitis C RNA in the small-scale study, showing an antiviral effect. Early stage clinical trials typically measure a drug's safety profile and whether it reaches its treatment target. The patient population is often too small to determine whether the drug candidate is actually effective.

The two companies plan a 14-day study on the drug in combination with two approved drugs, Pegasys and Copegus, also called ribavirin. An application was submitted to European regulatory authorities last month for the triple-combination study. Also, Roche has completed the tablet formulation of ITMN-191 and will use it in a midstage, or Phase II, clinical trial.

Shares of InterMune rose $2.84, or 19.1 percent, to $17.42. The stock has traded between $11.72 and $30.99 over the last 52 weeks.

Posted by Editors at 03:27 PM --- Printer-friendly version

March 28, 2008

New Experimental Drug Blocks Hep C Virus and Lowers Cholesterol

By interfering with RNA, drug company Santaris may have launched a new generation of drugs. Following a successful animal trial, an unusual new drug has sparked interest due to its ability to lower cholesterol and block the Hepatitis C virus.

Drug lowers cholesterol and fights hepatitis C

By Steve Connor
Thursday, 27 March 2008

www.independent.co.uk

A drug that can lower cholesterol levels and prevent the liver from being attacked by the hepatitis C virus has come a step closer following a successful trial on laboratory animals.

The drug works in an unusual way by interfering with the natural genetic mechanism in the cells of the liver that keeps cholesterol levels high and – coincidentally – allows the hepatitis virus to replicate within the organ. The study, which was carried out on African green monkeys, lowered cholesterol levels by up to 40 per cent over three months with the help of just three intra-venous injections given over five days at the start of the trial.

Each injection contained a watery solution of a short, single-stranded molecule of RNA – a close relative of DNA – which found its way to the liver and bonded with a similar type of RNA which is found within the organ's cells. This prevented the natural RNA from working normally, boosting the activity of certain genes, which lowered cholesterol and blocked the hepatitis C virus.

The study, published in Nature, was carried out by the Danish drug company Santaris. Scientists believe the findings support the idea of a new generation of drugs based on the ability to interfere with the natural functions of RNA.

Human trials of the new drug are expected to begin later this year.

Posted by Editors at 10:49 AM --- Printer-friendly version

March 20, 2008

Therapeutic Hepatitis C Vaccine Gets Its First Human Safety Marks

Currently in clinical trials for safety, the first human has completed treatment on the therapeutic DNA vaccine known as ChronVac-C®. By utilizing an innovative electroporation-based DNA delivery system, ChronVac-C® now has concrete evidence of its safety and ability to invoke the desired immune response against Hepatitis C.

Hepatitis C Virus DNA Vaccine Shows Safety When Delivered by Inovio Biomedical’s Electroporation Delivery System in Phase I/II Clinical Study at Karolinska University Hospital

March 17, 2008

www.businesswire.com

SAN DIEGO--(BUSINESS WIRE)--Inovio Biomedical Corporation (AMEX:INO), a leader in enabling the development of DNA vaccines using electroporation-based DNA delivery, announced today that its partner, Tripep AB of Sweden, has reported preliminary results from the first patient to complete treatment with Tripep’s therapeutic hepatitis C virus (HCV) vaccine, ChronVac-C®, which was delivered using Inovio’s electroporation-based DNA delivery system. In this phase I/II clinical study, the treatment has so far been safe and tolerable. Samples taken before, during and after treatment showed that before vaccination the patient did not have a detectable cell-mediated immune response against HCV but such an immune response became detectable after treatment was completed. Inovio’s electroporation delivery technology is intended to enhance the potency of DNA-based immunotherapies, including DNA vaccines, against cancers and infectious diseases.

ChronVac-C® is a therapeutic DNA vaccine being given to individuals already infected with hepatitis C virus with the aim to clear the infection by boosting a cell-mediated immune response against the virus. It is known that patients who spontaneously clear their infection have also developed this type of immune response.

This clinical study is being conducted at the Infectious Disease Clinic and Center for Gastroenterology at the Karolinska University Hospital in Huddinge and Solna (Sweden), respectively. Intended enrollment is 12 patients divided into three dose groups with increasing doses of ChronVac-C®. Each patient receives four ChronVac-C® vaccinations one month apart. After the last vaccination, patients are followed for another six months. The study’s main purpose is to assess safety. It is also testing whether the treatment boosts the immune response to HCV and its effect on virus replication in the liver. If the patient is completely virus-free six months after completing treatment, he/she will be considered cured. This first reported data was from the first patient in the lowest dose group. Five patients have been treated and no unexpected side effects have been observed.

“We are pleased that this first infectious disease DNA vaccine to be delivered in humans using electroporation-based DNA delivery has provided initial evidence of being safe and inducing a cell mediated immune response against the hepatitis C virus,” stated Avtar Dhillon, MD, Inovio’s president and CEO. “We look forward to seeing additional data, particularly from the higher dose groups, relating to this potential treatment to a pervasive and difficult-to-treat disease.”

About Hepatitis C and ChronVac-C

Hepatitis is a disease characterized by inflammation of the liver. Hepatitis C virus (HCV) is spread primarily by direct contact with human blood, the major causes worldwide being the use of unscreened blood transfusions and re-use of inadequately sterilized needles and syringes. As many as 70% - 90% of newly infected patients may progress to develop chronic infection (WHO: 2002). Of those with chronic liver disease, 5% - 20% may develop cirrhosis. About 5% of infected persons may die from the consequences of long term infection (due to liver cancer or cirrhosis). Globally, an estimated 170 million people are chronically infected with HCV, representing a reservoir sufficiently large for HCV to persist, and 3 to 4 million persons are newly infected each year. In the US, while new incidences of HCV have dropped dramatically, an estimated 4.1 million Americans have been infected with HCV, of whom 3.2 million are chronically infected (Centers for Disease Control and Prevention: 2006). The total market for therapies against hepatitis C infections is estimated to be over 2 billion dollars and is expected to grow to more than 8 billion dollars by 2015.

HCV infections in the liver do not trigger an immune response very effectively. Certain antiviral therapies, while expensive, are somewhat effective in treating hepatitis C. There is no vaccine currently available to prevent hepatitis C. ChronVac-C(R) is a therapeutic DNA vaccine designed with the aim of stimulating the body's immune system. Animal experiments demonstrated that ChronVac-C vaccination activated B-cells and T-cells (the latter being regarded as the most significant to clearing the chronic infection relating to hepatitis C) that killed cells producing HCV protein. In humans, the ChronVac-C DNA plasmid is being injected into muscle tissue, where vaccinations are usually given, and taken up by muscle cells with the assistance of Inovio's electroporation-based DNA delivery system. These muscle cells are expected to produce predetermined antigens that may activate the body's immune system to attack all cells producing HCV proteins.

About Tripep AB

Tripep AB is a Swedish biotechnology research company that develops and commercializes candidate drugs based on patented and proprietary technologies. Its main focuses are research and clinical development of ChronVac-C(R), a therapeutic vaccine against hepatitis C; preclinical research focusing on the development of therapeutic and prophylactic vaccines against influenza A and HIV; and the RAS(R) technology platform. More information is at www.tripep.se. Contact Jan Nilsson, CEO, at +46 8 449 8480 or jan.nilsson@tripep.se.

About Inovio Biomedical Corporation

Inovio Biomedical (AMEX:INO) is focused on developing multiple DNA-based immunotherapies and DNA vaccines. Inovio is a leader in developing human applications of electroporation which uses brief, controlled electrical pulses to increase cellular uptake of a useful biopharmaceutical. Human data has shown that Inovio’s electroporation-based DNA delivery technology can significantly increase gene expression and immune responses from DNA vaccines. Immunotherapy partners include Merck, Wyeth, Vical, University of Southampton, Moffitt Cancer Center, the U.S. Army, National Cancer Institute, and International Aids Vaccine Initiative. Inovio’s technology is protected by an extensive patent portfolio covering in vivo electroporation. More information is available at www.inovio.com.

This press release contains certain forward-looking statements relating to our plans to develop our electroporation drug and gene delivery technology. Actual events or results may differ from our expectations as a result of a number of factors, including the uncertainties inherent in clinical trials and product development programs (including, but not limited to, the fact that clinical results referenced in this release may not be indicative of results achievable in other trials or for other indications and that results from one study may necessarily not be reflected or supported by the results of other similar studies), the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of Inovio’s technology as a delivery mechanism, the availability or potential availability of alternative therapies or treatments for the conditions targeted by Inovio or its collaborators, including alternatives that may be more efficacious or cost-effective than any therapy or treatment that Inovio and its collaborators hope to develop, evaluation of potential opportunities, issues involving patents and whether they or licenses to them will provide Inovio with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether Inovio can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of our technology by potential corporate or other partners or collaborators, capital market conditions, and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2007, and other regulatory filings from time to time. There can be no assurance that any product in our product pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proved accurate.

Inovio Biomedical
Bernie Hertel, 858-410-3101 (Investors)
or
Ronald Trahan Associates Inc.
Ron Trahan, 508-359-4005 ext. 108 (Media)

Posted by Editors at 09:18 AM --- Printer-friendly version

February 12, 2008

Will STAT-C Replace Today's HCV Standard Therapy?

Experts in the field agree that STAT-C drugs combined with pegylated interferon and possibly ribavirin are the future for treating Hepatitis C. Learn more about STAT-C, as well as the three factors limiting interferon treatment.

by Nicole Cutler, L.Ac.

A new era of medical technology is currently emerging for Hepatitis C treatment. The development of specifically targeted antiviral therapy for Hepatitis C (STAT-C) is rapidly advancing and will revolutionize the way this virus is treated.

Today’s standard treatments are based on interferon, a medication that works by modifying the immune system response. However, by targeting the Hepatitis C virus, STAT-C uses a more direct approach than interferon-based therapies.

Although several therapeutic regimens have been developed to treat Hepatitis C, they all focus on interferon. The current standard of care for the treatment of Hepatitis C is combination therapy with pegylated interferon-alfa and ribavirin. While this combination regimen boasts an 80 percent success rate for those infected with Hepatitis C genotype 2, only about 40 percent undertaking this therapy achieve success with genotype 1, the most common Hepatitis C subtype in North America. Hepatitis C treatment programs centered on interferon are limited by three primary factors:

1. Side Effects – Enduring interferon treatment is a challenge; approximately 50 percent of patients are forced to reduce the dosage or stop treatment prematurely due to the severity of side effects.

2. Efficacy – Interferon’s effectiveness is limited; of those who are able to complete treatment at full dosage, approximately only 50 percent achieve sustained virologic response (SVR), otherwise known as an undetectable viral load.

3. Duration – The amount of time in treatment is long; duration times typically range from six months to one year.

Concerns about the efficacy and tolerability of standard peginterferon/ribavirin therapy suggest there is a significant medical need for improved therapies for Hepatitis C. As supported thus far by clinical trial results, the hope for STAT-C is to improve on the three factors limiting interferon treatment: improvement in viral elimination, higher patient tolerability and shorter treatment duration.

Instead of stimulating the body’s natural immune response to the virus, STAT-C directly attacks the Hepatitis C virus. Similar to some of the drugs used to treat HIV, these new medications thwart the enzymes needed for the virus to reproduce.

Resistance
Drug resistance is one of the larger obstacles STAT-C must contend with. Similar to HIV therapy, the antiviral agents composing STAT-C possibilities are limited by being prone to drug resistance. When the virus alters itself to avoid extinction, drug resistance renders the drug useless and makes the new strain even harder to eliminate. However, researchers have found that Hepatitis C resistance may be delayed or prevented by using combinations of potent antiviral drugs without cross-resistance profiles and optimizing patient adherence to therapy.

The Contenders
In terms of possible new anti-virals in the pipeline, the medications thus far are targeting two enzymes required for Hepatitis C reproduction: serine protease and polymerase. Known as Hepatitis C protease and polymerase inhibitors, the early clinical data on this class of drugs is encouraging despite issues of toxicity and virus resistance. Inhibiting these two enzymes has emerged as preferred contenders in the realization of STAT-C.

· Protease Inhibitors – Examples of protease inhibitors currently being developed and tested include SCH503034, VX-950 (Telaprevir), VX500, R7227, ITMN-191, ACH-1095 and TMC435350. While a few of these have been abandoned or altered due to their potential toxicity, the clinical promise of protease inhibitors is enormous. Especially when combined with pegylated interferon alfa-2a and ribavirin, most studies recruiting this triple combination demonstrate superiority in rapid Hepatitis C viral load decline.

· Polymerase Inhibitors – Examples of polymerase inhibitors currently being developed and tested include GS9190, GSK625433, R7128, R1626, VCH-759, MK-0608, IDX-184, A-837093, and AG-021541. While some reports on these agents to date have revealed drug resistance and gastrointestinal side effects, the bottom line is polymerase inhibitors have the potential to dramatically drop viral load in a short period of time. As their evaluation continues, an increasing number of researchers are combining polymerase inhibitors with pegylated interferon alfa-2a for greater efficacy.

It is important to remember that many investigational agents never make it out of the development pipeline, either due to suboptimal efficacy or poor safety. However, incorporating the approaches of enzyme inhibition with immune therapy may provide a cure for a substantial percentage of people with Hepatitis C. Experts in the field agree that STAT-C drugs combined with pegylated interferon and possibly ribavirin are the future for treating Hepatitis C.

We can expect that therapy for Hepatitis C will become more complicated, similar to highly active antiretroviral therapy (HAART) used to fight HIV infection. Also like HAART, physicians and researchers must be cautious working with STAT-C, as the virus may become more sophisticated and resist the medications used. Although STAT-C is not a single-pill cure-all, its ability to reduce viral load in a relatively short period of time will revolutionize how Hepatitis C is treated.

References:

http://hcvdrugs.com, Hepatitis C New Drug Pipeline, hcvdrugs.com, 2008.

Sulkowski, MS, Specific targeted antiviral therapy for hepatitis C, Current Gastroenterology Reports, March 2007.

www.hcvadvocate.org, AASLD: Investigational Antiviral Therapies for Hepatitis C, Liz Highleyman, Hepatitis C Support Project, 2007.

www.hcvadvocate.org, Hepatitis C Treatments in Current Clinical Development, Alan Franciscus, January 2008.

www.medscape.com, Specifically Targeted Antiviral Therapy (STAT-C) for Patients With Chronic Hepatitis C, Zobair M. Younossi, MD, MPH, FACP, FACG, Medscape, 2007.

www.projectsinknowledge.com, Revolutionizing the Way We Treat HCV: Stat-C, Ira M. Jacobson, MD, John G. McHutchison, MD, FRACP, Jean-Michel Pawlotsky, MD, PhD, Charles M. Rice, PhD, Projects In Knowledge, Inc., 2007.

Posted by Editors at 02:17 PM --- Printer-friendly version

January 14, 2008

ANA598 Shows Potential as an HCV Anti-Viral Drug

Animal studies of Anadys Pharmaceutical's new non-nucleoside Hepatitis C inhibitor have delivered some hopeful results. Although the subjects were primates, ANA598's demonstration of rapid viral load decline, favorable pharmacokinetics, safety, and tolerability profiles support its continued development.

Anadys Pharmaceuticals Announces Positive Results for ANA598 in Animal Model of Chronic Hepatitis C Virus Infection

ANA598 demonstrates significant antiviral activity in vivo
January 03, 2008: 05:49 PM EST

http://money.cnn.com

SAN DIEGO, Jan. 3 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. announced preliminary data today from two studies of ANA598, a non-nucleoside inhibitor of the hepatitis C virus (HCV) NS5B polymerase, in a primate model of chronic HCV infection.

Two animals chronically infected with HCV genotype 1b each received once-daily oral doses of ANA598 at 30 mg/kg for four days. A rapid viral load decline was seen in both animals. At 48 hours (24 hours after the second dose), viral load declines were 2.2 and 2.6 log10 in the individual animals. In one animal the viral load reduction was sustained throughout the remaining dosing period, while in the second animal a modest rise in viral load was seen over days 3 and 4, although the rise observed (0.6 log10) was within the baseline variability seen in this animal prior to dosing.

In a previous study conducted to assess the pharmacokinetics (PK), safety, tolerability and preliminary antiviral activity of ANA598, two HCV genotype 1a infected animals received a single oral dose of ANA598 at 30 mg/kg. At 24 hours after dosing, plasma levels of ANA598 exceeded the replicon EC95 values. At 48 hours after dosing, the mean viral load decline in the two animals was 1.0 log10. ANA598 was well tolerated by all of the animals in both studies.

"These positive animal efficacy data reinforce our continued enthusiasm for development of ANA598 as a potential new direct antiviral treatment for chronic HCV," said Steve Worland, Ph.D., President and Chief Executive Officer of Anadys. "The rapid viral load decline and the favorable PK, safety and tolerability profile demonstrated in these animal efficacy studies further support continued development of ANA598 as a candidate for use in combination with other agents for the treatment of chronic HCV infection."

In June 2007, Anadys announced the nomination of ANA598 as a clinical development candidate. The selection of ANA598 represented the culmination of a comprehensive structure-based drug design program directed towards NS5B. ANA598 was selected based on an optimized balance of preclinical properties, including intrinsic potency as an NS5B inhibitor, cellular activity in the replicon assay, oral bioavailability and early indicators of safety and tolerability. ANA598 is a low-nanomolar inhibitor of HCV genotype 1a and 1b replicons. It exhibits good in vitro metabolic stability properties and does not significantly inhibit or induce cytochrome P450 enzymes. In vivo, ANA598 was well tolerated in 14-day dose range finding (DRF) animal toxicology studies. At doses corresponding to estimated human doses, 24 hour trough plasma concentrations of ANA598 exceeded the EC95 for HCV genotype 1a and 1b replicon inhibition. The EC95 is the concentration required in vitro to suppress hepatitis C viral RNA levels by 95% in the replicon assay.

ANA598 is currently completing IND enabling activities and an IND submission is targeted for the second quarter of 2008. "After completing the necessary IND enabling studies, we look forward to exploring the potential clinical utility of ANA598," said James Freddo, MD, Anadys' Chief Medical Officer. "Based on the in vitro and in vivo potency, pharmacokinetic and preliminary toxicologic properties of ANA598 demonstrated to date, we believe that this is an exciting new direct antiviral to investigate for the treatment of patients with hepatitis C virus infection."

About Anadys

Anadys Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to improving patient care by developing novel medicines in the areas of hepatitis C and oncology. The Company is developing ANA598, a small-molecule, non-nucleoside inhibitor of the NS5B polymerase for the treatment of chronic hepatitis C virus (HCV) infection and ANA773, an oral TLR7 agonist prodrug for cancer.

Safe Harbor Statement

Statements in this press release that are not strictly historical in nature constitute "forward-looking statements." Such statements include, but are not limited to, references to the expected timing and planned development activities for ANA598 and the belief that ANA598 is an exciting new direct antiviral to investigate for the treatment of patients with HCV infection. Such forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause Anadys' actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. For example, the results of preclinical studies, including the animal studies described in this press release, may not be predictive of future results, and Anadys cannot provide any assurances that any of its product candidates will not have unforeseen safety issues, will have favorable results in future clinical trials or will receive regulatory approval. In addition, Anadys' results may be affected by risks related to competition from other biotechnology and pharmaceutical companies, its effectiveness at managing its financial resources, its ability to successfully develop and market products, difficulties or delays in its preclinical studies or clinical trials, difficulties or delays in manufacturing its clinical trials materials, the scope and validity of patent protection for its products, regulatory developments involving future products and its ability to obtain additional funding to support its operations. Risk factors that may cause actual results to differ are more fully discussed in Anadys' SEC filings, including Anadys' Form 10-K for the year ended December 31, 2006 and Anadys' Form 10-Q for the quarter ended September 30, 2007. All forward-looking statements are qualified in their entirety by this cautionary statement. Anadys is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.

Posted by Editors at 10:25 AM --- Printer-friendly version

January 02, 2008

Weight-Based Ribavirin Dosing = Superior Hepatitis C Treatment

A substantial, five-year study confirms that when it comes to treating Hepatitis C, one size does not fit all. When combined with pegylated interferon, researchers discovered basing the dosage of ribavirin on a patient's weight could yield better results than giving all participants a flat dosage of ribavirin. In addition, the weight-based ribavirin dosage demonstrated a clear advantage to African Americans with Hepatitis C, whose outcomes has previously lagged behind those of Caucasian patients.

Weight-based Dosing Of Ribavirin Improves Outcomes For Patients With Hepatitis C

www.sciencedaily.com

ScienceDaily (Oct. 26, 2007) — Patients with hepatitis C treated with combination therapy of pegylated interferon and ribavirin had better outcomes when taking a weight-based dosage of ribavirin compared to a flat dosage. This treatment technique also improved the response rates of African American patients, whose outcomes have lagged behind those of Caucasian patients. These findings are in the October issue of Hepatology, a journal published by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases (AASLD).

Combination therapy of pegylated interferon and ribavirin is the standard of care for patients with chronic hepatitis C, allowing more than half to achieve a sustained viral response. However, previous studies have suggested that a weight-based dose of ribavirin might lead to even better results. To examine this possibility, researchers, led by Ira Jacobson of Cornell University, conducted a large, multi-center, randomized, prospective, open-label study between December 2000 and June 2005.

They enrolled 5,027 patients with hepatitis C from more than 200 centers around the country. All participants were 18 to 70 years old, weighed less than 125 kg, had detectable HCV RNA in their blood, and had never been treated for it. They were randomly assigned to receive interferon and a flat dose of ribavirin (800 mg/day), or interferon and a weight-based dose of ribavirin, which started at 800 mg/day for patients weighing under 65 kg, and increased by 200 mg/day for up to each additional 20 kg of weight up to a maxiumum dose of 1400 mg. Those with HCV genotype 2 or 3, which is more responsive to interferon-based therapy, also tested treatment durations of 24 and 48 weeks. Each patient was followed up for 24 weeks after treatment.

"A sustained viral response was achieved by significantly more patients who received a weight-based dose (44.2 percent) than fixed dose (40.5 percent) ribavirin," the authors report. "Overall, response rates decreased as weight increased when a fixed dose was used but remained unaltered with a weight-based dose." Discontinuation rates and reported adverse events did not differ significantly between the two treatment schemes, and relapse rates were lower for patients who had received weight-based dosing. The researchers also found that 48 weeks of treatment offered no additional benefit compared to 24 weeks for patients with genotypes 2 or 3..

Another group of researchers from the same study, also lead by Jacobson, used the study data to understand the impact of weight-based ribavirin with peginterferon alfa-2b in African American patients with HCV genotype 1. Genotype 1 is the hardest to treat, and it afflicts African Americans disproportionately.

Three hundred eighty seven African American patients with genotype 1 were included in the analysis: of those weighing 65 kg or more, and therefore receiving different doses of ribavirin in each arm, 188 had received flat-dose ribavirin, and 174 had received weight-based dosing. Significantly fewer patients in the flat-dose group (10 percent) attained a sustained virological response, compared to 21 percent in the flat-dose group. Relapse rates were 30 percent and 22 percent, respectively.

"An unexpected finding of our study was the increase in efficacy with an increase in ribavirin dose in heavier patients," the authors report. That is, sustained viral response rates increased as body weight increased, suggesting that "ribavirin distribution may be more complex than realized and body weight may only approximate the marker for size required to dose RBV consistently," the authors say.

In conclusion, weight-based dosing of ribavirin offered a significant advantage in efficacy of treatment for African American patients, however, the rate of sustained viral response in this population remains low. "Further studies are needed to elucidate the fundamental basis for the impaired responsiveness in this population," they say.

In an accompanying editorial, Steven-Huy Han, MD and Jason Smith, PharmD of Los Angeles, report that this study adds significantly to our understanding of interferon therapy in African American patients. It will change the approach to ribavirin dosing and will benefit a difficult-to-treat population.

They suggest that the larger question of whether true weight-based dosing of ribavirin is superior to the currently approved standard dosing schemes still awaits head-to-head studies to answer. "At the minimum," they conclude, "the traditional notion that ribavirin dosage should be fixed has now been sidelined by the idea that we should tailor ribavirin dosing to our patients."

Article: "Peginterferon alfa-2b and Weight-Based or Flat-Dose Ribavirin in Chronic Hepatitis C Patients: A Randomized Trial." Jacobson, Ira; Brown, Robert; Freilich, Bradley; Afdhal, Nezam; Kwo, Paul; Santoro, John; Becker, Scott; Wakil, Ed; Pound, David; Godofsky, Eliot; Strauss, Robert; Bernstein, David; Flamm, Steven; Pauley, Mary Pat; Griffel, Louis; Brass, Clifford A. Hepatology; October 2007; (DOI: 10.1002/hep.21932).

Adapted from materials provided by John Wiley & Sons, Inc.

Posted by Editors at 04:12 PM --- Printer-friendly version

November 29, 2007

HCV Treatment Aided by New Platelet-Boosting Drug

In collaboration with health centers across the globe, researchers at Duke University Medical Center are excited about a once daily pill for increasing blood platelet counts. To help patients complete antiviral therapy, the researchers found that eltrombopag effectively raises blood platelets in those with low platelet counts and cirrhosis of the liver due to Hepatitis C.

Drug boosts platelets in hepatitis C patients
www.eurekalert.org

November 28, 2007

DURHAM, N.C. – It’s not a cure, but this may be some of the best news patients infected with the hepatitis C virus (HCV) have heard in a long time: A new drug, eltrombopag, appears to be effective in boosting low platelet counts, one of the major reasons why patients can’t endure antiviral treatments.

Other drugs that can restore normal platelet functions are infusions or injections; eltrombopag is a pill taken just once a day.

Researchers at Duke University Medical Center and other centers world-wide studied eltrombopag (marketed as Promacta in the U.S. and Revolade in Europe by GlaxoSmithKline) in 74 patients with low platelet counts and cirrhosis of the liver due to HCV infection. They found that it boosted platelet counts in a majority of patients at each of three dosage levels, enabling most of them to continue or start conventional antiviral treatment.

The findings appear in the current issue of the New England Journal of Medicine.

“We feel this is an important development for many people infected with the hepatitis C virus world-wide,” says Dr. John McHutchison, professor of medicine and associate director of the Duke Clinical Research Institute. “A significant number of patients with HCV infection will at some point develop platelet problems that will compromise their getting the best treatments we have. Anything we can do to prevent that from happening would improve their care.”

It’s estimated that 4 million people in the U.S. and 170 million world-wide carry the hepatitis C virus. The virus causes inflammation and scarring in the liver, and while it is curable in about half of those who have it, it can lead to significant liver damage, liver cancer and death in others. HCV infection is a common cause of cirrhosis and the most common reason for a liver transplant.

Platelets are cells made in the bone marrow that are important in clot formation, and serious bleeding can occur if platelet levels fall too low. Some diseases, like HCV infection, can cripple the body’s ability to manufacture platelets, but so can some medical treatments. Cancer patients, for example, can experience plummeting platelet levels when undergoing chemotherapy.

In the phase II, multi-center trial, participants were randomized to a control group or to receive 30, 50, or 75 milligrams of eltrombopag daily. The patients had platelet levels ranging from 20,000 to 70,000 (145,000 to 450,000 is normal).

A phase II trial is designed to test the safety and efficacy of a drug at different doses, and the Duke study found that eltrombopag worked in a dose-dependent manner, meaning that patients got a better response with increasing amounts of the drug. Seventy-four percent of those in the trial who took the lowest dose saw their platelet counts go up significantly, while 79 percent and 95 percent of the participants saw increases with the higher doses.

Eltrombopag does cause side effects. Some of the patients complained of headaches, dry mouth, abdominal pain and nausea.

“We are encouraged by these results and are already working on another multi-center, international, phase III trial where we hope these results will be confirmed,” says McHutchison.

###

The study was sponsored by GlaxoSmithKline, which manufactures eltrombopag. McHutchison and many of the coauthors also report having received grants, consulting, advisory or speaking fees from the company.

Colleagues who contributed to the study include Geoffrey Dusheiko, M.D., Royal Free Hospital, London; Mitchell Schiffman, M.D., Virginia Commonwealth University Medical Center; Maribel Rodriguez-Torres, M.D., Fundacion de Investigacion de Diego, San Juan; Samuel Sigal, M.D., Weill Medical College; Marc Bourliere, M.D., Hopital St. Joseph, Marseille; Thomas Berg, M.D., Charite, Berlin; Stuart Gordon, M.D., Henry Ford Hospital and Health System, Detroit; Fiona M. Campbell, B.Sc., GlaxoSmithKline, Greenford, UK; Dickens Theodore, M.D., M.P.H., GlaxoSmithKline, Research Triangle Park; Nicole Blackman, Ph.D. and Julian Jenkins, M.Sc.,GlaxoSmithKline, Philadelphia; and Nezam Afdhal, M.D., Beth Israel Deaconess Medical Center, Boston.

Contact: Michelle Gailiun
michelle.gailiun@duke.edu
919-660-1306
Duke University Medical Center

Posted by Editors at 12:05 PM --- Printer-friendly version

November 09, 2007

Eliminating HCV in Previous Non-Responders

Molecularly different than pegylated interferon, consensus interferon offers hope to non-responders. This retrospective study on U.S. veterans with Hepatitis C demonstrates that those with Hepatitis C RNA remaining after interferon-ribavirin therapy may have another option for future treatment.

Consensus Interferon in Hepatitis C Is an Option for Those Non-Responsive to Peginterferon/Ribavrin: Presented at AASLD

By Maria Bishop

BOSTON, MA -- November 7, 2007 -- In a recent retrospective study of veterans, 12% of hepatitis C virus (HCV) subjects remained HCV ribonucleic acid (RNA) undetectable at least 3 months post-treatment with consensus interferon (Infergen) following prior treatment with peginterferon and ribavirin, researchers reported here at the 58th Annual Scientific Meeting of the American Association for the Study of Liver Disease (AASLD).

Treatment-naïve veterans fared better, with 24% remaining HCV RNA undetectable at least 3 months post-treatment with consensus interferon, noted lead author Helen S. Yee, PharmD, Ambulatory Care Clinical Pharmacist, Pharmacy Service, Department of Veterans Affairs (VA) Medical Center, San Francisco, California, United States.

These data offer an alternative for patients who are nonresponders/relapsers to peginterferon plus ribavirin. At least 50% of chronic HCV patients who receive standard therapy are nonresponders to treatment, added Dr. Yee.

Seven-hundred seventy-six of the hepatitis C patients who were reviewed for this study had been prescribed consensus interferon with ribavirin (99.7%) or without ribavirin in the VA health care system from October 2003 to October 2006. Treatment duration varied significantly between prescribers, and over 57% of the patients in this study discontinued consensus interferon within less than 3 months of starting treatment. The mean treatment duration averaged 3.1 months.

Data were reviewed for documentation of the following: HCV antiviral treatment history and response; time between HCV antiviral treatments; consensus interferon dose, frequency, and duration; and HCV RNA results. Demographic data were also included. The mean age of patients (95.4% of whom were male) was 55.4 ± 5.57 years. The average prior peginterferon treatment duration (n = 646) was 8.9 months.

"Factors associated with outcomes and consensus interferon [with or without ribavirin] -- such as dosing, length of treatment, and other practice variations -- need to be further assessed," concluded Dr. Yee.

This trial was funded in part by the VA National HIV/Hepatitis C Program and a grant from Valeant Pharmaceuticals, makers of Infergen.

[Presentation title: Hepatitis C Virus (HCV) Treatment Outcomes with Consensus Interferon with or without Ribavirin in Peginterferon/Ribavirin Non-responders/Relapsers: Results from National Clinical Practice Settings. Abstract 355]

Posted by Editors at 02:59 PM --- Printer-friendly version

November 08, 2007

Locteron Showing Promise for Hepatitis C

OctoPlus has reported positive results from a Phase IIa trial for the Hepatitis C drug Locteron. Thus far, Locteron is encouraging due to its convenient dosing schedule, tolerability and Hepatitis C anti-viral activity.

OctoPlus says hepatitis C drug effective in study
Tue Nov 6, 2007

AMSTERDAM (Reuters) - Dutch biotechnology firm OctoPlus said on Tuesday European safety and efficacy Phase IIa studies have shown an antiviral effect for its chronic hepatitis C drug Locteron.

"A statistically significant dose response was observed in the study," the company said in a statement, adding that the drug was tolerated at all doses.

The company, which has four other products in pre-clinical and clinical development, said approximately 90 percent of adverse events were rated as mild.

OctoPlus is co-developing Locteron with its partner Biolex Therapeutics, which plans to commence a European safety and efficacy Phase IIb trial of the drug in mid-2008.

With Locteron, OctoPlus is aiming to develop a treatment for patients with chronic hepatitis C, with fewer side effects and a more convenient dosing schedule compared with current therapies.

(Reporting by Harro ten Wolde)

Posted by Editors at 02:44 PM --- Printer-friendly version

November 07, 2007

Encouraging HCV Results Issued by Roche

Delivering encouraging news, pharmaceutical giant Roche shares results of two of its leading HCV drugs. As the result of a Phase IIa trial that combined Pegasys and Copegus with R1626, the Hepatitis C virus was undetectable in 81 percent of the study's participants. In collaboration with Pharmasset, a Phase I study of R7128 also demonstrated great promise against the virus.

Roche Issues Hepatitis Drug Data
www.thestreet.com

By Elizabeth Trotta
Staff Reporter
11/2/2007

Roche said Friday that in a phase IIa study a triple-drug combination for treatment of hepatitis C showed a robust virological response and subsequently will proceed to a phase IIb study.

Presenting results at the American Association of the Study of Liver Diseases (AASLD) meeting in Boston, the Swiss drugmaker said its investigational hepatitis C drug R1626 showed promising antiviral activity in the phase IIa trial when given with Pegasys (peginterferon alfa-2a) and Copegus. The aforementioned Roche drugs are used together to treat adults with chronic hepatitis C whose liver still works normally and who haven't been previously treated with an interferon alpha.

After four weeks of treatment with the three-drug combination, the virus couldn't be detected in 81% of patients with a mean decrease in viral load of 5.2 log10 from the baseline, and Roche said most adverse events were mild to moderate.

Also, no resistance to R1626 was identified following intensive testing for either two weeks of treatment with R1626 as monotherapy or in patients treated with R1626 for four weeks in combination with the standard of care.

The phase IIb study, called POLI 1, which will further investigate R1626 in combination with standard or lower dose of Pegasys and standard dose of Copegus, is now open and enrolling patients in eight countries, including the U.S.

Pharmasset (VRUS - Cramer's Take - Stockpickr), which partners with Roche to develop chronic hepatitis C drug R7128, presented data Friday on a phase I 14-day monotherapy study of patients who failed to respond to standard therapy. Pharmassest said there was a 99% mean decrease in HCV with no serious adverse events. (Pharmasset divulged positive preliminary results for the study in September.) The companies are hoping those results will translate when the drug is used in combination with other therapies for a longer duration in a previously untreated population.

Gilead (GILD - Cramer's Take - Stockpickr - Rating), Idenix, (IDIX - Cramer's Take - Stockpickr - Rating) and ViroPharma (VPHM - Cramer's Take - Stockpickr - Rating) are also developing candidates in a class of antivirals called polymerase inhibitors for hepatitis C virus.

Vertex (VRTX - Cramer's Take - Stockpickr - Rating), which is presenting at AASLD as well, also dished hepatitis C data for its Telaprevir on Friday.

Posted by Editors at 01:58 PM --- Printer-friendly version

October 24, 2007

Boceprevir Trial Delivers Hopeful News for Hepatitis C

Preliminary results from a Phase II trial on Schering-Plough's experimental Hepatitis C drug Boceprevir are promising. If the results of this study prove to be reproducible and the drug is safe, Boceprevir may help many more people defeat the Hepatitis C virus.

Schering says data on hepatitis C drug promising

NEW YORK, Oct 18 (Reuters) - Schering-Plough Corp (SGP.N: Quote, Profile, Research) on Thursday reported promising early results from a mid-stage study involving its experimental hepatitis C drug, boceprevir.

The company said the favorable results were seen in a Phase II trial of patients who had never previously been treated for their infections with the liver-damaging hepatitis C virus.

One group of patients received boceprevir along with Schering-Plough's widely used current dual therapy -- the injectable interferon drug Peg-Intron and anti-viral pill ribavirin -- while another group received only Peg-Intron and ribavirin.

After 12 weeks of treatment, up to 79 percent of patients in the boceprevir group had undetectable levels of the virus in their bloodstreams, compared with 34 percent of those taking only Peg-Intron and ribavirin.

The company noted that the results, although encouraging, were only preliminary. (Reporting by Lewis Krauskopf and Ransdell Pierson, editing by Gerald E. McCormick)

Posted by Editors at 01:41 PM --- Printer-friendly version

October 23, 2007

Recent Findings Present New Strategy to Fight Hepatitis C

California biologists have recently discovered that a defense mechanism known to operate in other species also helps humans fight the Hepatitis C virus. MicroRNA interference explains how interferon inhibits Hepatitis C replication and will likely lead pharmaceutical companies on a new path for developing future treatments.

Discovery Of New Antiviral Mechanism Promising For Hepatitis C Treatment

www.sciencedaily.com

ScienceDaily (Oct. 22, 2007) — A team of researchers led by biologists at the University of California, San Diego has discovered a completely new mechanism that mammalian cells employ to fight infections of the Hepatitis C virus, which affects approximately 2.7 million Americans and 170 million people worldwide.

The achievement, detailed in a paper published in the October 18 issue of the journal Nature, could improve current antiviral regimens or result in new treatments that are more effective and possess fewer detrimental side effects for those with the Hepatitis C virus infection, which frequently leads to liver cirrhosis and/or liver cancer.

“Approximately two percent of the human population worldwide is infected with Hepatitis C virus,” said Michael David, an associate professor of biological sciences at UC San Diego who headed the research team. “And about 50 to 80 percent of those people develop persistent infections and are at great risk of developing liver cancer.”

The only approved therapy for Hepatitis C is alpha-interferon, a protein produced by animal cells when invaded by viruses that induces healthy cells to manufacture enzymes that counter the infection. Often alpha-interferon is used in combination with an antiviral drug called ribavirin. However, only 40 to 80 percent of patients respond to this therapy and about half of those who do respond relapse once interferon treatments are stopped. Only about 25 percent of those treated with interferon, which can also induce flu-like symptoms and kidney damage in some patients, rid themselves of the viral infections. Explaining these varying response rates is difficult, since scientists do not fully understand the mechanisms used by alpha-interferon to fight off Hepatitis C virus infection.

What David and his team discovered is that microRNAs, short strands of RNA that interfere with the expression of specific genes, may also be effective against the Hepatitis C virus, because they are used by mammalian cells to reduce the replication of the virus. Their discovery comes as a surprise because while microRNA interference has been known to occur as a defense mechanism in plants and invertebrates, many scientists doubted it was employed by mammalian cells.

David and his group began by identifying microRNAs whose expression is controlled by alpha-interferon, then used computer prediction to identify potentially affected viral RNAs. Hepatitis C virus emerged as a prime candidate and the UCSD researchers--in collaboration with Hepatitis expert Francis Chisari of The Scripps Research Institute--demonstrated that several alpha-interferon induced microRNAs are able to potently inhibit viral infection and replication.

“This is an entirely new antiviral mechanism in mammalian organisms,” said David. “Use of synthetic microRNAs has become a promising strategy of antiviral treatment. However, selecting the ‘right’ sequence is crucial in order to avoid unwanted and potentially dangerous side effects. The microRNAs used by alpha-interferon have been selected by evolution for efficacy and safety,and might therefore provide a sound basis for the generation of new synthetic antivirals.”

“Now that we have identified this new antiviral pathway or mechanism, pharmaceutical companies may be able to design a more effective therapy against the Hepatitis C virus,” said Irene Pedersen, a project scientist working in David’s laboratory who is the first author of the paper.

Other co-authors of the paper are Francis Chisari, Guofeng Cheng and Stefan Wieland of The Scripps Research Institute and Carlo Croce and Stefano Volinia of Ohio State University. The research was supported by grants from the National Institutes of Health.

Adapted from materials provided by University of California, San Diego.

Posted by Editors at 11:30 AM --- Printer-friendly version

October 17, 2007

Hepatitis C Vaccine Ready for Phase I Trial

A potential Hepatitis C vaccine is beginning Phase I trials in Canada and France. Known as TG4040, this gene-based vaccine will be evaluated for safety and immune response in ribavirin/interferon non-responders and those who have yet to attempt Hepatitis C treatment.

New Therapeutic Vaccine May Offer Hope for Chronic Hepatitis C Patients

www.associatedcontent.com

According to a press release, everything is ready and set to test a new vaccine that may offer hope for people who suffer from Hepatitis C and have relapsed after standard treatment.

Standard treatment consists of treatment with Ribavirin and Pegylated-Interferon Alpha for about six months. Some patients may fail at this standard treatment and may have a relapse in the disease. Additionally, and according to the press release, standard treatment is effective in 50% of the patients completing therapy, is lengthy and often poorly tolerated.

Transgene therapeutic vaccine candidate TG4040 (MVA-HCV) is set to be tried (Phase I trial) on approximately 24 patients that are chronically infected with the Hepatitis C Virus (HCV) and who have relapsed after standard treatment. The trial will be done in Canada.

The protocol for this clinical trial class for one subcutaneous injection of TG4040 per week over a 3-week period together with a boost injection at Month 6. Safeety and immunity responses will be the hallmarks of this study.

The safety data, as well as preliminary viral and immunological data, is planned to be available for the public by end of 2008. Another Phase I study of TG4040 is currently being performed in France on 15 Hepatitis C patients who have never received any other therapy for their condition. Preliminary results are expected at the end of 2007.

Hepatitis C is a blood-borne, infectious, viral disease that is caused by a hepatotropic virus called Hepatitis C virus (HCV). An estimated 150-200 million people worldwide are infected with hepatitis C. In the U.S., those with a history of intravenous drug use, inhaled drug usage, tattoos, or who have been exposed to blood via unsafe sex or social practices are increased risk for this disease. Hepatitis C is the leading cause of liver transplant in the United States (Ryan and Ray 2004).

Sixty to Seventy per cent of people infected develop no symptoms during the acute phase (first 6 months). Some patients experience acute phase symptoms but they are usually mild and rarely lead to a specific diagnosis of hepatitis C. Symptoms of acute hepatitis C infection include decreased appetite, fatigue, abdominal pain, jaundice, itching, and flu-like symptoms.

What is TG4040?

TG 4040 is a recombinant MVA vaccine virus containing nucleotide sequences encoding non-structural immunogenic NS3, NS4 and NS5B proteins of the hepatitis C virus.

Who is Transgene?

Transgene is a biopharmaceutical company dedicated to the discovery and development of gene-based therapeutic vaccines and immunotherapy products for the treatment of cancer and infectious diseases. In addition to TG4040, Transgene has other products in the pip-line such as vaccines candidates for Non Small Cell Lung Cancer, Cervical Intraepithelial Neoplasia (CIN 2-3), and Cutaneous B-cell Lymphoma.

Sources:

Transgene extends therapeutic vaccine candidate TG4040 development program against chronic Hepatitis C. Transgene Press Release. URL: http://www.transgene.fr/us/pdf/communique_presse/communiques_divers_2007/PR-US_%20TG4040_01-10-07.pdf

Ryan KJ; Ray CG (editors) (2004). Sherris Medical Microbiology, 4th ed., McGraw Hill, pp. 551-2.

Transgene web site. URL: http://www.transgene.fr/fr/index.php

By Rafael B.
Published Oct 01, 2007

Posted by Editors at 12:51 PM --- Printer-friendly version

September 19, 2007

Lowering Hep C Viral Load in Non Responders

Pharmasset's nucleoside polymerase inhibitor, R7128, will begin a new round of testing following its positive Phase 1 results. In addition to appearing safe and well-tolerated, R7128 is showing potential to lower Hepatitis C viral load in non-responders.

AFX News Limited

Roche's US partner Pharmasset says hepatitis C trial drug decreases virus level

09.10.07, 10:37 AM ET
www.forbes.com

ZURICH (Thomson Financial) - Roche Holdings AG's US partner Pharmasset Inc said hepatitis C trial drug R7128 successfully lowered the level of the virus in patients who failed to respond to interferon therapy.

The phase I clinical study was carried out for 14 days on 40 patients, with R7128 showing 'potent antiviral activity' as well as being safe and well tolerated, Pharmasset (nasdaq: VRUS - news - people ) said. Dosages used in the study were 750 mg or 1500 mg.

New Jersey based Pharmasset is collaborating with Roche to develop the drug, and based on the results of the trial will start a 28-day study of R7128 in combination with interferon Pegasys plus Copegus.

R7128 is classed as a nucleoside polymerase inhibitor, a new generation of antivirals being developed to treat hepatitis C patients.

sarah.fenwick@thomson.com

Posted by Editors at 09:23 AM --- Printer-friendly version

September 04, 2007

Future HCV Medication and Vaccine from Japan

Using inactivated Hepatitis C particles, a Japanese company has successfully suppressed the Hepatitis C virus in mice. This scientific development holds enormous potential as a Hepatitis C vaccine and possibly as a therapeutic medication for those already infected.

Toray develops Hepatitis C vaccine
28 August 2007

www.domain-b.com

The Tokyo-headquartered Toray Industries, Inc, has announced that it has successfully confirmed for the first time in the world that hepatitis C virus (HCV) particles produced using a novel HCV culture system inactivated have the potential for practical use as an HCV vaccine in experiments using mice.

The culture system was established through the company's joint research on the development of an HCV vaccine with the National Institute of Infectious Diseases (NIID) at Shinjuku-ku, in Tokyo and the Tokyo Metropolitan Institute for Neuroscience (TMIN), Tokyo Metropolitan Organization for Medical Research (Fuchu, Tokyo).

Hepatitis C is a refractory viral infection of the liver. It occurs when HCV infects hepatocytes, and can lead to chronic hepatitis, to hepatic cirrhosis, and eventually to hepatocellular carcinoma. According to a WHO survey, it is estimated that 170 million people worldwide were carriers of HCV in 1999 with reportedly 3 to 4 million people being newly infected with HCV every year. Although a combination therapy of interferon and an antiviral drug, ribavirin, is currently used to treat hepatitis C, the development of new vaccines is urgently required to prevent the spread of HCV infection and eradicate the virus.

Vaccines to prevent infection with viruses occasionally contain component protein, part of the viruses, but whole forms of the attenuated viruses are often used successfully in vaccines such as influenza vaccines and polio (poliomyelitis) vaccines. For HCV, however, the inability to grow the virus under in vitro culture conditions has made it difficult to develop a vaccine.

Since its success in the in vitro cultivation of HCV for the first time in the world in 2005 jointly with TMIN, Toray has been seeking the potential of HCV particlest for use as an HCV vaccine in collaboration with NIID. Based on the research it has conducted, the company has successfully increased the efficiency of HCV production by 10,000 times through the research by preparing and using a human liver cell line which produces more HCV particles than conventional cells producing HCV particles.

Moreover, the company confirmed that the HCV infection of cultured human hepatocytes was suppressed by the serum which was obtained from the mice injected with inactivated HCV particles.

Based on the confirmation of the possibility of using these inactivated HCV particles as a HCV vaccine, the company will continue to work with NIID for further research and development to optimize the HCV particles for a vaccine and establish a culture method appropriate for industrial production.

The HCV vaccine is expected to not only become a new prophylactic drug to prevent new HCV infection, but also serve as a therapeutic drug for HCV-infected people. The company hopes that this HCV vaccine will be very good news for millions of patients suffering from hepatitis C worldwide.

Under its corporate slogan "Innovation by Chemistry", Toray is engaged in the expansion of its advanced materials with a focus on the life science field. The company aims for further expansion of its life science business positioned as one of "Strategically Developing Businesses," by promoting innovation of research and development employing its own advanced technologies.

send this article to a friendToray Industries, Inc. is going ahead with this research with the support of the Japan Health Sciences Foundation (Project for the fiscal years 2004 to 2006, "Establishment of hepatitis C virus infection and replication systems to develop effective anti-viral strategies") and the Ministry of Health, Labour and Welfare (Project for the fiscal years 2004 to 2006, "Development of vaccines using hepatitis C virus cell lines which allow infection, replication, and particle formation in cultured cells").

Posted by Editors at 10:26 AM --- Printer-friendly version

August 28, 2007

Clinical Trial, New Drug for Hepatitis C Viral Infection

Learn about Implicit Bioscience's drug, Oglufanide Disodium, now in a Phase IIa clinical trial to test its ability for overpowering Hepatitis C.

Drug in New Hepatitis C Clinical Trial

www.earthtimes.org

RISBANE, Australia, Aug. 24 /PRNewswire/ -- Physicians at Southern Health have started a phase IIa clinical trial designed to test the efficacy of a new strategy for defeating hepatitis C viral infection, one of the toughest infectious diseases in the modern world.

Implicit Bioscience's drug, oglufanide disodium, which works as a regulator of the body's immune response, is being given by intranasal administration to patients with chronic hepatitis C viral infection.

"The drugs currently in use fail to control this disease in about one half of all patients," said Dr Ian Frazer, Implicit's Chief Scientific Officer. "So there is a compelling need for new and better therapies, and we hope that oglufanide disodium may control or reverse the suppression of the immune system which the hepatitis virus uses to defeat our normally healthy defenses."

Dr Frazer is well known as the co-inventor of the recently approved vaccine for papillomavirus, which is designed to prevent cervical cancer.

Dr William Sievert, who is the Principal Investigator for the trial, welcomed the opportunity to study the action of oglufanide disodium in his busy liver diseases clinic at the Monash Medical Centre, which is part of the Southern Health network. "It is an important opportunity for patients to be involved in a new trial such as this, in which new treatment prospects are explored."

Oglufanide disodium was originally developed to treat severe infectious disease in Russia (where it is a registered pharmaceutical), and was extensively studied in cancer clinical trials in the United States before being acquired by the privately-owned Brisbane biotech company Implicit Bioscience Pty Ltd in 2005.

The phase IIa trial of intranasal oglufanide disodium will complement the ongoing phase Ib study of subcutaneously administered drug at the Princess Alexandra Hospital in Brisbane.

Oglufanide disodium regulates the body's innate immune response to defeat invading germs and cancer cells. The drug is also under development by Implicit as a biodefense therapy and for ovarian cancer.

Implicit Bioscience, Inc.

Posted by Editors at 12:00 PM --- Printer-friendly version

August 24, 2007

Alinia Tablets and Hepatitis C

For HCV genotype 1 patients who have failed to respond to standard therapy (peginterferon and ribavirin), Romark Laboratories has designed a clinical trial to test the safety and effectiveness of Alinia (nitazoxanide). Learn more about the Phase II clinical trial during which nitazoxanide tablets are administered in combination with Pegasys and Copegus, in 60 patients with the most common genotype in North America.

RxTrials Institute Drug Pipeline Alert
Aug. 20, 2007 | Vol. 5 No. 163
http://fdanews.com

Romark Begins Trial of Alinia for Chronic Hepatitis C

Romark Laboratories has initiated a Phase II clinical trial of Alinia for treating chronic hepatitis C in the U.S.

According to Romark, the clinical trial is designed to evaluate the effectiveness and safety of Alinia (nitazoxanide) tablets administered in combination with Pegasys (peginterferon alfa-2a) and Copegus (ribavirin) in 60 patients with chronic hepatitis C genotype 1 who have failed to respond to standard therapy (peginterferon and ribavirin).

The trial is part of the company’s Studies to Evaluate Alinia for Treatment of Hepatitis C (STEALTH C) clinical development program, a series of clinical trials designed to evaluate the safety and efficacy of Alinia tablets in combination with peginterferon or peginterferon and ribavirin in patients with chronic hepatitis C.

The trial is designed to evaluate the effectiveness and safety of Alinia administered 500 mg twice daily for four weeks followed by Alinia-Pegasys-Copegus combination therapy for 48 weeks compared to placebo for four weeks followed by placebo-Pegasys-Copegus combination therapy for 48 weeks, which is the standard of care.

Posted by Editors at 04:21 PM --- Printer-friendly version

August 15, 2007

New Treatment Recommended for Asian Chronic Hepatitis C Patients

The Chinese University of Hong Kong recently made public the results of its three-year study, which evaluated the use of interferon beta-1a and its combination with ribavirin in the treatment of Asian chronic Hepatitis C patients. Find out how it compares to the existing peginterferon-alfa based therapy.

New treatment for chronic hepatitis C leads to less side effects: study

August 14, 2007
http://english.people.com.cn

A study result made public Monday by the Chinese University of Hong Kong reveals that combination of interferon beta-1a and ribavirin treatment for chronic hepatitis C creates less side effects.

Chronic hepatitis C is an important cause of liver cirrhosis and liver cancer. Currently, the standard treatment of chronic hepatitis C is combination of peginterferon-alfa and ribavirin, which, however, leads to common adverse effects including fever and flu-like symptoms, injection site reaction, depression and bone marrow suppression. This decreases patients' compliance and in turn reduces the treatment effect, the university said.

The university hence carried out a three-year study to assess the use of interferon beta-1a and its combination with ribavirin in the treatment of Asian chronic hepatitis C patients.

About 250 Asian chronic hepatitis C patients with active disease were recruited and randomly assigned into two groups which received placebo treatment and interferon beta-1a plus ribavirin combination treatment respectively for 12 weeks, it said.

The result shows that interferon beta-1a and ribavirin combination treatment can achieve a similar rate of viral clearance but a low rate of adverse event and patient discontinuation as compared to the existing peginterferon-alfa based treatment.

The university recommended that interferon-beta-1 and ribavirin combination treatment be considered as an alternative to the existing peginterferon-alfa based therapy for Asian patients with chronic hepatitis C infection.

Source: Xinhua

Posted by Editors at 01:42 PM --- Printer-friendly version

August 06, 2007

New Technology and Methods to Fight Hepatitis C

Recent technology has allowed researchers to safely and effectively kill blood-borne diseases. In July 2007, researchers announced favorable results in Ultraviolet Blood Irradiation (UBI) outside the body. Discover what scientists have to say about using this new method to fight Hepatitis C and AIDS.

by Nicole Cutler, L.Ac.

The purpose of light goes beyond warming the earth’s surface or illuminating a room. Referred to by scientists as electromagnetic radiation, light has wavelengths both visible and invisible to the human eye. Various attempts to help people fight Hepatitis C have included electromagnetic radiation, with reports of success spanning both visible and invisible light.

Invisible Light
With shorter wavelengths than visible light, ultraviolet (UV) radiation is a confirmed environmental human carcinogen. While our sun emits light at all different wavelengths in the electromagnetic spectrum, ultraviolet waves are the portion of light responsible for causing sunburns. However, UV radiation used specifically to target Hepatitis C and other illnesses has been recognized for its potential healing ability.

Ultraviolet Blood Irradiation
Ultraviolet radiation is well-known to purify and deodorize air, sterilize water and destroy bacteria in waste products. First introduced in the 1930s to combat the polio virus, Ultraviolet Blood Irradiation (UBI) was used to remove infections from a person’s bloodstream. Although problems with sterile equipment hampered its success, UBI was considered the first line of defense against infection until the advent of antibiotics and polio’s Salk vaccine.

In modern times, the prevalence of new viral epidemics without a cure or vaccine, including Hepatitis C, has brought back this alternative form of healing. Due to more recent developments in the instrumentation for UBI, controlled application of UV irradiation to the blood within the accepted therapeutic band of light has produced favorable results for infectious diseases of the blood. Additional benefits of UBI are the ability to annihilate several pathogens from the blood at once, and the absence of side effects typically caused by antibiotics or anti-viral medications.

In 2005, Energex Systems, Inc. conducted a successful trial of this technology by reducing viral loads in patients with Hepatitis C. Under investigational device exemption status granted by the U.S. Food and Drug Administration, the trial subjects all had significant viral loads who had previously received Interferon/Ribavirin therapy without a sustained response to treatment.

Researchers extracted three to four percent of the patient’s blood, exposed it to exact amounts of UV light for 20 to 30 minutes, and then returned the irradiated blood to the patient. In each subject, this procedure was repeated five times over a 16-day period. Measured ten weeks after completion of therapy, the results were as follows:

· Three subjects sustained viral load reductions of 90 percent or more
· Eight subjects sustained reductions of 50 percent or more
· Two subjects had no change

While no treatment-related complications from this trial were reported, critics of UBI claim that exposing viruses to UV light can cause genetic mutations. Since a mutation of the Hepatitis C virus would render it even more resistant to therapies currently in development, UBI therapy has remained a fringe alternative therapy in the United States.

Visible Light
Visible light is light that can be perceived by the human eye. When looking at the visible light of the sun, it appears to be colorless, which we call white. Although this light is visible, white light is not considered to be part of the visible spectrum because it is not of a single color or frequency. Instead, white light is a combination of many color frequencies.

In July 2007, scientists from Arizona State University and Johns Hopkins School of Medicine discovered a new method aimed at safely and effectively killing viruses. By using an intense pulse of visible light, the researchers claim that mechanical vibrations rock the virus shell (capsid) causing irreversible damage to its reproduction and ending in the virus’ disintegration. Since UV irradiation is known to cause viral mutations and damage to the DNA of surrounding, healthy cells, the use of visible light is turning heads in the fight against infectious diseases.

The researchers used a power density of 50 megawatts per square centimeter, a quantity low enough to leave surrounding human cells and tissue undamaged, but high enough to produce large-amplitude vibrations in a virus's capsid. It was also too low to cause genetic mutations, meaning the virus would not build up resistance to this treatment over time.

According to Kong-Thon Tsen of Arizona State University and his colleagues, this method may be especially important in designing novel treatments for blood-borne viral diseases. By irradiating a patient’s blood outside the body, cleansing it of infection, and then reintroducing it back to the patient, mortality associated with diseases like Hepatitis C and AIDS can be greatly reduced.

As medical science refines its use of light’s amazing properties, people with Hepatitis C are likely to benefit. While UBI has been an alternative treatment helping people for many years, the risk of mutating a virus or healthy cells has prevented it from being a popular choice. However, as this technology is refocused on the spectrum of visible light, the risks of irradiating blood may disappear and Hepatitis C may finally meet its match.

References:

O’Brien, CB, et al., Extracorporeal photopheresis alone and with interferon-alpha2a in chronic hepatitis C patients who failed previous interferon therapy, Digestive Diseases and Sciences, May 1999.

http://en.wikipedia.org, Ultraviolet, Wikimedia Foundation, Inc., 2007.

http://in.news.yahoo.com, Visible light pulses to zap HIV, Hepatitis C, Ani-Asian News International, July 2007.

http://science.howstuffworks.com, How Light Works, Craig Freudenrich, PhD, How Stuff Works, Inc., 2007.

http://science.hq.nasa.gov, Ultraviolet Waves, National Aeronautics and Space Administration, 2007.

www.fflt.org, Understanding UV Light Therapy, Health and Wellness Foundation, 2007.

www.hemophilia.org, New Therapy Reduces Hepatitis C Viral Loads in Trial, Drug Law Weekly, National Hemophilia Association, April 2005.

www.newscientisttech.com, Visible light pulses knock out viruses in blood, Belle Dume, July 2007.

www.venicehousepizza.com, IBC Hospital - Blood Ultraviolet Irradiation, Victor Loustaunau MD, Serenelli Desktop Publishing, December 2003.

Posted by Editors at 02:24 PM --- Printer-friendly version

August 01, 2007

Mistletoe, Iscador® and Hepatitis C

Learn about mistletoe's therapeutic applications, including convincing evidence for its potential role in preventing long-term complications associated with Hepatitis C.

by Nicole Cutler, L.Ac.

As the most prevalent infectious disease of the liver, an estimated 3 percent of the world’s population carries Hepatitis C. Over time, Hepatitis C infection can lead to liver cancer, liver failure or cirrhosis—irreversible and potentially fatal scarring of the liver. Since only a small percentage of those infected can be cured, medical pioneers are striving to find innovative ways for inhibiting the virus’ growth and preventing these long-term complications from developing.

While researchers are hard at work to develop new drugs for treating and preventing the advancement of Hepatitis C, complementary medical practitioners are always investigating alternative, less toxic means for achieving the same goal. When it comes to alternative medical treatments, European physicians often lead the way. Used as a cancer therapy in Europe since the 1920s, the extract of mistletoe is often administered to people battling various types of illnesses.

Mistletoe
Most people associate mistletoe with the leafy, flowering vine to kiss underneath during the Christmas holiday. However, mistletoe is also used medicinally with a wide array of therapeutic applications ranging from epilepsy, infertility, hypertension, cancer, hepatitis and certain connective tissue disorders. Rudolf Steiner first advocated a special preparation of mistletoe to be injected for cancer treatment. In lectures to doctors in the early 1920s, Steiner mentioned the immune system as an important defense mechanism against cancer.

The Immune Link
The immune system’s role in defeating Hepatitis C and fighting cancer is very similar. Every day, hundreds of cells in our body degenerate because of viral infections or genetic changes, both which can become cancerous. Various types of white blood cells, including natural-killer cells, recognize these harmful cells and destroy them. A healthfully functioning immune system defends against the formation of tumors daily with this process.

In cancer patients, this function of the immune system has been weakened rendering it unable to eliminate cancerous cells. According to Steiner, when prepared in a special way and then injected, the mistletoe enhances the immune system by killing off cancerous cells and cells which are damaged by a viral infection or toxic influences from the environment.

Iscador®
An unlicensed, experimental drug, Iscador® is the trade name for an extract of mistletoe produced by the Hiscia Institute in Switzerland and Weleda in the U.S. In test-tube studies Iscador® has been shown to do the following:

· Improve the ability of immune cells to engulf foreign organisms.
· Increase natural-killer cell activity against foreign organisms or infected cells that have been “tagged” by antibodies.

In many countries, including those within the European Union, Iscador® is a licensed medication for monotherapy and as an adjuvant therapy in cancer treatment. Because mistletoe is potentially poisonous, Iscador® must be prescribed and administered by a physician.

Treatment
The common route of administering Iscador® is via injection just under the skin. As each day of therapy progresses, a more concentrated version is administered. A short-term fever is a typical effect of Iscador® injections. Many doctors theorize that this fever is a sign of immune system activation, an indication that Iscador® is working. Upon reaching the highest concentration of Iscador®, the injections typically continue for a week or longer, depending upon the clinical situation as judged by the treating physician. The most common side effects of Iscador® therapy include low-grade fever, redness and irritation at the injection sites.

Efficacy for Hepatitis C
Although used for decades as an alternative cancer therapy, reports of Iscador’s results for treating liver disease are primarily anecdotal. Evidence of this treatment helping people with Hepatitis C is limited to shared observations by physicians and recipients. While a few scientifically controlled medical trials have been conducted on Iscador® for this purpose, there is not yet enough proof for Iscador’s general acceptance by the American medical community. Although more human research on Iscador® is warranted, the existing evidence is compelling:

· A 2005 study in the Netherlands evaluated 21 patients with chronic Hepatitis C who were treated with a mistletoe preparation as monotherapy for one year. The treatment was well tolerated by the participants and significantly lowered liver enzyme levels. Although few effects on viral load were seen, researchers concluded that mistletoe’s ability to improve liver inflammation could reduce the likelihood of long-term complications developing in people with Hepatitis C.

· A 2001 study also from the Netherlands evaluated 5 patients with chronic Hepatitis C who were treated for one year with Iscador®. Two patients showed 6-20 fold decreases in viral load and normalization of liver inflammation. The treatment was well tolerated meaning that no serious side effects were observed. The authors concluded that Iscador® has potential as a non-toxic therapy for chronic Hepatitis C treatment.

Because of its route of administration and possible toxicity, Iscador® can only be obtained, administered and monitored by a licensed physician. As this is not a mainstream pharmaceutical therapy, doctors of naturopathic medicine are the most likely type of doctor to work with Iscador®.

Until a Hepatitis C cure that works for everyone is available, healthcare practitioners will exhaust every sensible option to conquer this disease. Although there is not yet enough evidence to conclude Iscador® is a person’s best choice to prevent Hepatitis C’s long-term complications like cirrhosis or liver cancer, it is an option to keep our eyes on.

References:

Mansky PJ, Mistletoe and Cancer: Controversies and Perspectives, Seminars in Oncology, December 2002.

Tusenius KJ, et al, Exploratory study on the effects of treatment with two mistletoe preparations on chronic hepatitis C, Arzneimittel-Forschung, 2005.

Tusenius KJ, et al., Iscador Qu for chronic hepatitis C: an exploratory study, Complementary Therapies in Medicine, March 2001.

www.aidsmap.com, Iscador, NAM Publications, 2007.

www.cancure.org, Iscador/Mistletoe, The Cancer Cure Foundation, 2007.

www.healthy.net, Two Studies of Iscador, Robert Gorter, MD, HealthWorld Online, 2007.

www.mayoclinic.com, Hepatitis C, Mayo Foundation for Medical Education and Research, 2007.

www.selfgrowth.com, Iscador: Victory Over Cancer, Phillip Minton, MD, Selfgrowth.com, April 2007.

www.usa.weleda.com, What is Iscador?, Weleda, 2007.

Posted by Editors at 02:14 PM --- Printer-friendly version

July 23, 2007

Will Fast Hepatitis C Diagnostic Test Meet FDA Approval?

On Thursday, July 19th, OraSure Technologies announced the positive performance of a rapid test that can detect the Hepatitis C virus in blood and saliva in just minutes. Learn when the company plans to finalize its clinical studies and file an application for U.S. FDA approval.

OraSure's hepatitis test on target

Company says its prototype performed well in trial.

By Sam Kennedy | Of The Morning Call
July 20, 2007

www.mcall.com

A hepatitis C test under development by OraSure Technologies of Bethlehem performed well in a recent trial, the company announced Thursday.

The news bodes well for OraSure's efforts to win governmental approval to sell a rapid hepatitis test that works similarly to the company's rapid HIV test. That test, called OraQuick, can detect the virus that causes AIDS in both saliva and blood in less than 20 minutes

Performance of the prototype hepatitis C test was shown to be as good as or better than that of currently available laboratory-based tests, the company said at the annual meeting of the American Association of Clinical Chemistry in San Diego.

''Our development efforts are proceeding on schedule, and we intend to begin the final clinical studies required to obtain FDA approval during the next several months,'' OraSure Chief Executive Doug Michels said in a press release.

He said OraSure plans to complete the studies and file an application for U.S. Food and Drug Administration approval in early 2008.

''Assuming we are successful, we expect that our test will be the first rapid [hepatitis C] test approved by the FDA for use in the United States,'' he said.

Hepatitis C kills as many as 10,000 Americans a year, a figure that is expected to double or triple in the next decade or so, surpassing annual AIDS deaths, according to the Centers for Disease Control and Prevention in Atlanta.

It is nonetheless known as a silent epidemic because infections often go undetected for years, even decades. The CDC estimates that 4.1 million people in this country, or nearly 2 percent of the population, have the disease, although fewer than half are aware of it.

The study described Thursday involved the testing of more than 1,000 blood and saliva specimens. According to OraSure, the prototype hepatitis C test performed with nearly 100 percent accuracy.

Posted by Editors at 05:00 PM --- Printer-friendly version

May 31, 2007

New Drug Shows Promise For Hepatitis C Genotype 1

Now in Phase II clinical trials, a new, oral HCV protease inhibitor, SCH 503034, may defeat the virus in interferon non-responders. Find out how well the drug is tolerated and how it is able to reduce the viral load of non-responders with genotype 1.

New HCV Protease Inhibitor Effective Against Hepatitis C

NEW YORK (Reuters Health) May 15 - A new, oral HCV protease inhibitor, SCH 503034, is well tolerated and may be effective against hepatitis C (HCV) genotype 1 that is refractory to interferon treatment, according to a report in the April issue of Gastroenterology.

SCH 503034 is a specific inhibitor of NS3 protease, which plays an essential role in the replication of HCV, the authors explain.

Dr. Christoph Sarrazin from Saarland University Hospital, Hamburg, Germany and associates evaluated the safety and tolerability of SCH 503034, alone and in combination with pegylated interferon-alpha-2b (IFN), in 26 patients with chronic HCV infection that had not responded to treatment with IFN with or without ribavirin.

Both as monotherapy and in combination with IFN, SCH 503034 was generally well tolerated, the authors report.

One week of treatment with SCH 503034 alone resulted in a mean maximal reduction in HCV RNA of 1.08 log10 at 200 mg 3 times daily, and 1.61 log10 at 400 mg 3 times daily, the investigators say.

Combination therapy with SCH 503034 and IFN resulted in greater decreases in HCV RNA than with IFN alone, the researchers note. The best results (a mean decrease in HCV RNA of 2.68 log10 after 2 weeks) were seen with the combination of SCH 503034 400 mg 3 times daily and IFN.

"Evaluation of virologic response during monotherapy and combination therapy suggests that combination SCH 503034 plus IFN was associated with anti-HCV activity in these patients who had previously not responded to IFN with or without ribavirin," the authors report.

"Phase II clinical trials with HCV genotype 1 nonresponders are underway to determine the optimum dosing and exposure levels for this potentially important therapeutic regimen," the researchers add.

"Novel oral antiviral approaches are exciting and fashionable," writes Dr. Jean-Michel Pawlotsky from Hopital Henri Mondor, Creteil, France in a related editorial. "The spectacular antiviral efficacy of some of these drugs should not, however, be allowed to mask the specific new problems they raise."

"Although adjunction of an oral HCV inhibitor may give interesting results, other options are already available for the treatment of chronic hepatitis C, including optimization of the current pegylated IFN-alpha-ribavirin combination," the editorial concludes. "All these options should be explored, as they may benefit patients in the near future."

Gastroenterology 2007;132:1270-1278,1611-1615

Posted by Editors at 11:35 AM --- Printer-friendly version

May 25, 2007

A Cure for Hepatitis C?

Spring 2007 brought a wave of health-related news professing a cure for Hepatitis C. While this publicity inspired hope in millions of people living with chronic HCV, it also sparked frustration and confusion. Learn more about the recent announcement that implied a cure for this disease, as well as what the details of the newsworthy study actually mean for you and your loved ones.

by Nicole Cutler, L.Ac.

According to Mitchell Shiffman, MD, professor in the Virginia Commonwealth University (VCU) School of Medicine, and chief of hepatology and medical director of the Liver Transplant Program at the VCU Medical Center:

“The use of peginterferon alone, or in combination with ribavirin, points to a cure for Hepatitis C, the leading cause of cirrhosis, liver cancer and the need for liver transplant. This paper strongly suggests, for the first time, that Hepatitis C is a curable disease. After treatment, 99.6 percent of the patients remained virus undetectable for over five years.”

Shiffman is one of the lead investigators in a study that was presented in May 2007 at the 38th annual Digestive Disease Week conference in Washington, D.C. Virginia Commonwealth University was among about 40 institutions worldwide studying pegylated interferon alfa-2a, manufactured by Roche, Inc.

The Study
The results are based on a long-term follow-up study designed to determine if the Hepatitis C virus reemerges in patients who have achieved treatment success. The study reviewed 997 patients, either infected with chronic Hepatitis C or co-infected with Hepatitis C and HIV. Those evaluated had already achieved a sustained virologic response following treatment with either PEGASYS (peginterferon alfa-2a) monotherapy or combination therapy with PEGASYS and ribavirin.

After successful treatment, researchers monitored blood levels of Hepatitis C once a year for an average of 4.1 years (range 0.4 to 7 years). Of the 997 patients, 989 maintained undetectable levels of the virus. Although the remaining eight patients tested positive for Hepatitis C at an average of two years following treatment completion, it is unknown why this occurred. Researchers have not determined if these eight patients experienced a relapse of the virus or if they were re-infected.

Sustained Virologic Response
Virginia Commonwealth University’s results are definitely cause for celebration among those who have persevered through PEGASYS treatment and achieved sustained virologic response (SVR). A course of treatment for Hepatitis C is considered successful when Hepatitis C RNA can no longer be detected in the blood. While Hepatitis C RNA may be undetectable immediately following treatment, this test must be repeated six months later to determine if any of the virus remained and reproduced. When the virus remains undetectable in the blood six months (or more) following Hepatitis C therapy, SVR is considered to be achieved.

The longer a person remains free of the virus, the more convinced health officials are that the person is not just in remission, but is actually cured of Hepatitis C. While most studies following Hepatitis C patients for two to three years after they’ve reached SVR reflect a low relapse rate, the results from VCU cement the notion of a cure. By following and testing Hepatitis C patients with SVR for an average of four years, the realization that SVR is permanent is more believable.

The Catch
Understanding what VCU’s study results mean to people with Hepatitis C is creating a great deal of confusion.

· What it DOES mean – Those who have achieved SVR with PEGASYS therapy have a 99 percent chance of being cured of Hepatitis C.

· What it DOES NOT mean – Anyone with Hepatitis C can currently be cured.

While the pharmaceutical industry continues to concentrate on new and improved treatments for Hepatitis C, the fact remains that less than half of patients with the most common genotype in the U.S. undergoing PEGASYS treatment attain SVR. According to the manufacturer, two large clinical trials have been conducted to show the effectiveness of PEGASYS with ribavirin combination therapy in patients with Hepatitis C. These studies found, after 48 weeks of unaltered treatment:

· SVR was achieved by 53 percent of participants in one trial and 61 percent in the other.

· Among patients with genotype 1, the most prevalent genotype in the U.S., 44 percent of participants in one trial and 51 percent in the other achieved SVR. For those who had a high viral load, the success rate was even lower – 41 and 47 percent.

The percentage of trial participants achieving SVR does not include those who, due to side effects, dropped out of the study or who had their medication dosages lowered. Again, according to the PEGASYS manufacturer:

· In Hepatitis C monoinfection trials, 11 percent of patients discontinued therapy.

· In Hepatitis C monoinfection trials, 39 percent required modification of therapy.

· In the HCV/HIV coinfection trial, 16 percent of patients discontinued therapy.

· In the HCV/HIV coinfection trial, 39 percent of patients required modification of therapy.

Considering the overall statistics and likelihood of achieving SVR with PEGASYS therapy, the computations demonstrate that people with genotype 1 have approximately a 25 percent chance of being cured. This is because roughly 50 percent of people with Hepatitis C cannot complete the therapy at the full dosage level. Of the 50 percent who complete treatment, about half of those with genotype 1 achieve SVR.

Hope
Even though the majority of those who undergo the rigors of PEGASYS therapy do not attain sustained virologic response, the idea that Hepatitis C can be eliminated inspires hope. Now that we know that SVR lasts for four or more years and is likely permanent, researchers will shift their focus on making this cure attainable for everyone infected with Hepatitis C.

References:

www.forbes.com, Study Suggests Cure for Hepatitis C, HealthDay News, Forbes.com, LLC, May 2007.

www.pegasys.com, Effectiveness of PEGASYS (detailed), Hoffman- La Roche, Inc., 2007.

www.pegasys.com, Safety and Tolerability, Hoffman-La Roche, Inc., 2007.

www.sciencedaily.com, Cure For Hepatitis C Announced By Researcher, ScienceDaily, LLC, 2007.

www.terradaily.com, Total Hepatitis C Cure Possible, Ed Susman, United Press International, 2007.

Posted by Editors at 02:33 PM --- Printer-friendly version

May 09, 2007

New HCV Preferred Treatment

Human Genome Sciences and Novartis are working together to improve Hepatitis C treatment with the long acting version of interferon, Albuferon. The ongoing, Phase II study demonstrated that Albuferon has a success rate equal to, or better than pegylated interferon. Learn why Albuferon becoming the preferred treatment over pegylated interferon is good news for Hepatitis C patients.

Albumin Interferon May Be as Effective as Pegylated Interferon with Less Frequent Dosing

By Liz Highleyman
www.hivandhepatitis.com

Standard therapy for chronic hepatitis C using pegylated interferon plus ribavirin is often limited by drug-related toxicities such as flu-like symptoms and depression.

Both available forms of pegylated interferon alfa (Pegasys and PegIntron) are injected once weekly -- which is a considerable improvement over conventional interferon, which was administered 3 times per week. For some patients, less frequent injection is associated with fewer side effects and improved quality of life.

Human Genome Sciences and Novartis are collaborating on the development of an even longer-acting form of interferon alfa -- albumin interferon (Albuferon) -- which can be injected once every 2 weeks. Data from studies of albumin interferon were presented at the 42nd Annual Meeting of the European Association for the Study of the Liver last month in Barcelona, Spain.

Genotype 1 Patients

In a late-breaker session, Stefan Zeuzem, MD, presented data from an ongoing Phase IIb study evaluating the safety and efficacy of albumin interferon in treatment-naive genotype 1 chronic hepatitis C patients. A total of 458 subjects in 8 countries were randomly assigned to receive 1 of 3 doses of subcutaneous albumin interferon -- 900 or 1200 mcg once every 2 weeks (Q2W) or 1200 mcg once every 4 weeks (Q4W) – or else 180 mcg once-weekly Pegasys for 48 weeks; all patients also received ribavirin.

Interferon efficacy is usually assessed based on sustained virological response (SVR), or undetectable HCV RNA 24 weeks after the completion of therapy. Here, the researchers reported interim “SVR12” results 12 weeks after the end of therapy; follow-up is continuing.

Results

By intention-to-treat analysis, SVR12 rates in the various arms were as follows:

o Albumin interferon Q2W 900 mcg: 59.3%;
o Albumin interferon Q2W 1200 mcg: 55.5%;
o Albumin interferon Q4W 1200 mcg: 52.6%;
o Pegylated interferon: 54.4%.

Among subjects who achieved at least 80% adherence to prescribe interferon and ribavirin doses, SVR12 rates were higher across all arms, but the improvement was most pronounced in the Q2W albumin interferon arms:

o Albumin interferon Q2W 900 mcg: 73.8%;
o Albumin interferon Q2W 1200 mcg: 72.0%;
o Albumin interferon Q4W 1200 mcg: 67.5%;
o Pegylated interferon: 63.0%.

Among heavier patients (75 kg or more, a group that responds more poorly to therapy) with optimal adherence, SVR12 rates were maintained in the albumin interferon arms, but lower in the pegylated interferon arm:

o Albumin interferon Q2W 900 mcg: 80.6%;
o Albumin interferon Q2W 1200 mcg: 70.4%;
o Albumin interferon Q4W 1200 mcg: 66.7%;
o Pegylated interferon: 56.7%.

Among adherent patients, relapse rates were reduced in all albumin interferon arms, especially Q2W 900 mcg (13.0%), compared with pegylated interferon (29.7%).

Rates of premature discontinuation due to adverse events in the 4 arms were as follows:

o Albumin interferon Q2W 900 mcg: 9.3%;
o Albumin interferon Q2W 1200 mcg: 19.1%;
o Albumin interferon Q4W 1200 mcg: 12.1%;
o Pegylated interferon: 6.1%.

Quality of life as measured by the SF-36 scale was most favorable in the albumin interferon Q2W 900 mcg arm.

Conclusion

The researchers concluded that, “These data suggest that the Q2W albumin interferon regimens may offer at least comparable or increased efficacy, with an improved dosing schedule and the potential for less impairment in quality of life compared with Q1W pegylated interferon. The Q4W 1200 results warrant further investigation of Q4W dosing in clinical trials.”

J.W. Goethe-University Hospital, Germany; Hopital Pitie-Salpetriere, France; University of Alberta, Canada; Hadassah University, Israel; Monash University, Australia; Medical University of Bialystok, Poland; Spitalul Clinic de Adulti Cluj-Napoca, Romania; Nuselská poliklinika – Remedis, Czech Republic; University of British Columbia, Canada; University Of Manitoba, Canada; Duke Clinical Research Institute, Durham, NC; Human Genome Sciences, Rockville, MD.

Genotype 2 or 3 Patient

In a second study, V.G. Bain and colleagues assessed albumin interferon in treatment-naive patients with genotype 2 or 3 HCV. In this multicenter, open-label Phase II trial, 43 subjects were randomly assigned to receive subcutaneous albumin interferon at a dose of 1500 mcg either Q2W or Q4W plus 800 mg/day ribavirin. Patients were treated for 24 weeks, the standard duration of pegylated interferon therapy for these genotypes.

Rapid virological response rates at week 4 were 76% in the Q2W arm and 68% in the Q4W arm; after 24 weeks, however, the end-of-treatment response rates were 71% and 82%, respectively. Albumin interferon was well tolerated overall, with similar safety profiles in the 2 dose groups. There were no dose reductions in the Q4W arm compared with 10% in the Q2W. SVR data from this study are pending.

University of Alberta, Edmonton, Canada; University of Western Ontario, London, ON, Canada; University of Manitoba, Winnipeg, MB, Canada; University of British Columbia, Vancouver, BC, Canada; University of Calgary, Calgary, AB, Canada; Bar Ilan University, Ramat-Gan, Israel; Duke Clinical Research Institute, Durham, NC; Human Genome Sciences, Inc., Rockville, MD.

05/04/07

References

S Zeuzem, Y Benhamou, VG Bain, and others. Antiviral response at week 12 following competion of treatment with albinterferon alfa-2b plus ribavirin in genotype 1, IFN-naive, chronic hepatitis C patients. 42nd Annual Meeting of the European Association for the Study of the Liver (42nd EASL). Barcelona, Spain. April 11-15, 2007.

VG Bain, P Marotta, K Kaita. Comparable antiviral response rates with albumin interferon alfa-2b dosed at Q2W or Q4W intervals in naive subjects with genotype 2 or 3 chronic hepatitis C. 42nd EASL.

Posted by Editors at 01:42 PM --- Printer-friendly version

April 20, 2007

Progress in Stopping HCV Replication

Achillion recently revealed progress in preventing Hepatitis C viral replication. Although discontinued due to its strain on the kidneys, clinical trials with ACH-806 demonstrated potent HCV anti-viral activity. Find out how those results may shape the development of the next generation of drugs that carry the hope of finding a more effective HCV treatment.

Achillion Presents Positive Data on Novel Mechanism for Treating HCV at EASL Annual Meeting

PR Newswire Europe (inc. UK Disclose) - Apr. 16, 2007

NEW HAVEN, Conn., April 16 /PRNewswire-FirstCall/ -- Achillion Pharmaceuticals, Inc. today announced the presentation of data validating the clinical antiviral activity of one of Achillion's NS4A antagonists, ACH-806, for the treatment of hepatitis C virus (HCV) infection at the 42nd Annual Meeting of the European Association for the Study of the Liver (EASL). In three separate presentations, Achillion researchers discussed the potent antiviral activity in HCV-infected subjects, synergy with other classes of HCV inhibitors, and the unique mode of action of a NS4A antagonist. Achillion has shown that blocking NS4A, a viral protein that binds to a portion of HCV protease, inhibits HCV replication. This program is part of a collaboration and exclusive license agreement with Gilead Sciences for the research, development and commercialization of compounds for the treatment of chronic HCV.

In a late-breaker session on April 14th at 5:00 PM, John Pottage, M.D., Senior Vice President and Chief Medical Officer at Achillion, discussed clinical data in a presentation titled, "Short-term Antiviral Activity and Safety of ACH-806 (GS-9132), an NS4A Antagonist, in HCV Genotype 1 Infected Individuals." The randomized, double-blind, placebo-controlled dose-escalation trial measured the antiviral activity, safety and pharmacokinetics of 300 mg of ACH-806 or placebo, dosed orally twice daily as a monotherapy over 5 days. The mean change in HCV RNA (log10) at day 5 was a decrease of 0.91 from baseline for treated subjects versus an increase of 0.05 for control subjects. Elevations in serum creatinine (a marker of kidney function) were observed in ACH-806 treated subjects and were reversible after completion of dosing.

"This study provides the first demonstration of human antiviral activity of an NS4A antagonist for HCV," said Dr. Pottage. "While we and our partner Gilead decided to discontinue development of ACH-806 based upon the increase in serum creatinine levels, we do not believe this effect was target-related. The antiviral activity of the compound validates NS4A as a novel therapeutic target and therefore supports our continued work with Gilead to identify and evaluate next-generation compounds with the same mechanism of action."

A second presentation on April 12 at 6:30 PM, titled "In Vitro Evaluation of Combination Treatment of ACH-806 with Interferon, VX-950 and NM 107," was led by Mingjun Huang, Ph.D., Senior Director of Virology at Achillion, who discussed in vitro evaluations of ACH-806 in combination with interferon, a protease inhibitor, and a polymerase inhibitor. The data revealed that the NS4A antagonist did not show in vitro cross-resistance with agents from these other HCV therapeutic classes, and that NS4A antagonism appears to have a synergistic antiviral effect in combination in vitro with the HCV protease inhibitor VX-950 and the polymerase inhibitor NM 107.

Finally, in a third presentation on April 12 titled "ACH-806: A Potent Inhibitor of HCV Replication with a Novel Mechanism of Action," Dr. Huang described the novel mechanism of action of NS4A antagonists. Achillion's studies demonstrated that these antagonists block the formation of functional viral replication complexes, thereby preventing HCV replication independent of protease or polymerase inhibition.

"The high mutation rate of HCV necessitates the combination use of drugs with complimentary mechanisms of action in order to suppress viral resistance. Therefore, the possibility that candidates with the unique NS4A antagonism mechanism may be complementary to protease and polymerase inhibitors will be an important benefit in treating HCV infection," stated Pottage.

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April 04, 2007

Longer Lasting HCV Treatment in Phase I Trial

Since interferon medication is quickly broken down by a person's circulatory and digestive systems, its potency is typically short-lived. By resisting rapid breakdown, Nautilus Biotech's newly engineered interferon-alpha drug, Belerofon, shows promise in increased effectiveness against Hepatitis C. Now in a Phase I study, we will soon learn of Belerofon's safety and tolerability.

Nautilus Biotech Begins Phase I Clinical Trial In The USA For Subcutaneous Belerofon(R), Its Long-Lasting, Interferon-Alpha Drug

www.medicalnewstoday.com
Article Date: 03 Apr 2007 - 0:00 PDT

Nautilus Biotech has announced that it has initiated a Phase I clinical trial for subcutaneous Belerofon(R), its long-lasting human Interferon (IFN) alpha. Belerofon has therapeutic potential for the treatment of a number of conditions, including chronic Hepatitis C.

Following recent approval by the US Food and Drug Administration, the Phase I clinical trial is being held in Austin, Texas in the USA and involves six treatment groups of eight male and female volunteers, aged 18 to 50 years. The trial is an open-label, ascending dose study of four doses of subcutaneous (SC) Belerofon, which will be compared to SC administered IntronA(R) (a Schering-Plough product) and Pegasys(R) (pegylated Interferon alfa-2a (40KD), a Roche product).

The primary objective of the trial is to evaluate SC Belerofon in healthy adult subjects, for safety, tolerability and pharmacokinetics in comparison with IntronA and Pegasys. The second objective is to evaluate the comparative pharmacodynamics of the three products. Nautilus Biotech expects initial results from the trial to be available during Q3 2007.

Belerofon is an engineered variant of IFN-alpha. It has a single point mutation for lower sensitivity to protease-mediated degradation, unchanged molecular weight and specific antiviral activity compared to non-pegylated IFNs. Following subcutaneous administration in animals, SC Belerofon shows a longer half-life and subsequently improved exposure profile compared to native IFN alpha and pegylated derivatives.

"We are confident that Belerofon has the potential to set a new Gold Standard Interferon in the treatment and management of Hepatitis C," said Nautilus Biotech's CEO, Manuel Vega. "The start of a clinical trial for subcutaneous Belerofon is a major milestone in our move to become a leading drug development company."

"The commencement of a Phase I clinical trial for SC Belerofon represents an important development in our pipeline of novel engineered protein drugs," said Paul Martin, Nautilus Biotech's Vice President Strategy. "It demonstrates Nautilus Biotech's ability to move novel engineered proteins from design to the clinic quickly and efficiently."

In addition to the injectable Belerofon evaluated in this clinical study, Nautilus Biotech has formulated lyophilized Belerofon together with inactive ingredients to produce enteric-coated tablets for oral administration and filed an IND for oral Belerofon in February 2007. All currently marketed Interferon alpha drugs are administered by injection.

About Hepatitis C

Hepatitis C (HCV) is the most prevalent liver disease in the world. HCV infection causes chronic inflammation in the liver that can lead to cirrhosis, liver failure, liver cancer or death. HCV infection represents a significant medical challenge worldwide. Currently, there is no vaccine that can prevent hepatitis C.

According to the World Health Organization, more than 170 million people worldwide suffer from chronic HVC. With only half of all HCV patients benefiting from current therapy, there is considerable market potential for new medical solutions. The HCV market is expected to grow from $2.2 billion in 2005 to $4.4 billion in 2010 and $8.8 billion in 2015 due to improved market penetration and better diagnosis rates (source: Datamonitor).

About Nautilus Biotech

Nautilus Biotech is a drug discovery and development company with a pipeline of next-generation therapeutic proteins with superior pharmacological profiles that address unmet clinical needs. The company's protein engineering technology can significantly improve the pharmacological characteristics of important blockbuster protein drugs, offering improvements in drug stability and administration. The company is also creating proprietary 'third generation' therapeutic proteins which are, per se, suitable for oral administration.

The therapeutic proteins market is currently valued at over $35bn, and growing at a rate of 10-15% per annum. Nautilus Biotech has created a portfolio of next-generation therapeutic proteins with improved profiles, including long-lasting Interferon alpha (Belerofon), hGH (Vitatropin(R)), Interferon beta, Erythropoietin, Interferon gamma, Clotting Factor IX (in collaboration with Wyeth Pharmaceuticals) and HMGB1 (in collaboration with Creabilis Therapeutics). Nautilus Biotech has established a strong intellectual property position covering enhanced versions of these multibillion dollars molecules and is rapidly moving these products into clinical development.

Nautilus Biotech

Nautilus Biotech is a private company with headquarters in Genopole(R) biopark, (Evry, France). For more information about Nautilus Biotech visit http://www.nautilusbiotech.com/

Nautilus Biotech
http://www.nautilusbiotech.com/

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April 03, 2007

New Compound in Development for Patients with Chronic HCV

The results from the Phase I study with XTL-6865, a new compound being tested in patients with chronic Hepatitis C, are promising. In addition to the detailed outcome of this study, you'll learn how XTL-6865 may become a viable treatment option for patients with Hepatitis C undergoing liver transplantation, or for individuals with chronic Hepatitis C who have low viral loads.

XTL Announces the Completion of Phase I Study with XTL-6865 in Patients with Chronic Hepatitis C

29 Mar 2007
www.pipelinereview.com

XTL Biopharmaceuticals Ltd. announced today the completion of the Phase I study with XTL-6865.

NEW YORK, NY, USA | Mar 29, 2007| XTL Biopharmaceuticals Ltd. announced today the completion of the Phase I study with XTL-6865. The primary goal of this Phase I study was to evaluate safety and pharmacokinetic properties of XTL-6865 in patients with chronic hepatitis C. XTL-6865, which targets the E2 envelope protein of the hepatitis C virus, is comprised of two fully-human monoclonal antibodies and is administered intravenously. The study enrolled 32 patients into 8 cohorts, each comprised of 3 treated patients and 1 placebo patient. Of the 8 cohorts in the study, the first 7 were single administration cohorts with doses ranging from 5mg to 2400mg. The 8th cohort received 1200mg for 5 consecutive days.

In this study, XTL-6865 was shown to be safe at high doses (up to 1200mg for 5 consecutive daily doses and a single dose of 2400mg). The study also enabled the Company to establish the pharmacokinetic properties of XTL-6865 in patients with chronic hepatitis C. For all single doses, the t-max was reached immediately at the end of the XTL-6865 infusion. For the highest single dose, 2400mg, the C-max was between 500 and 1000 microg/ml and the t1/2 was approximately 5 days. For the lower single doses, the t1/2 was 2-3 days. The study provided evidence of binding of the antibody to circulating virus and the formation of immune complexes (antibody-virus), believed to be important for virus neutralization in the serum. No statistically significant changes in HCV-RNA were observed. Given the short duration of administration of XTL-6865, and the fact the patients in this study had a high rate of viral replication at baseline, no significant change in viral load was to be expected.

The results of this Phase I trial potentially pave the way for trials that would evaluate XTL-6865 in patients with hepatitis C undergoing liver transplantation - a potential target patient population for this drug - or in chronic hepatitis C patients with low viral load. XTL intends to seek a collaborative partnership for the future development of this compound.

Ron Bentsur, CEO of XTL Biopharmaceuticals, commented, "This trial enabled us to determine the pharmacokinetic properties of XTL-6865, and to demonstrate that it could be safely administered to patients at high doses. This study also clearly demonstrated that the antibody binds to the circulating virus in the serum. We believe that XTL-6865 could potentially play a role in certain clinical settings, such as preventing re-infection of hepatitis C following liver transplantation or in chronic hepatitis C patients who have low viral loads following treatment with other anti-hepatitis C drugs. We believe this is now an appropriate time to seek to out-license the compound." Mr. Bentsur continued, "We intend to focus our resources on commencing our clinical program for Bicifadine, for the treatment of diabetic neuropathic pain, and on completing our Phase I study for XTL-2125, our small-molecule compound for the treatment of chronic hepatitis C."

About XTL Biopharmaceuticals Ltd.

XTL Biopharmaceuticals Ltd. ("XTL") is engaged in the acquisition, development and commercialization of therapeutics for the treatment of neuropathic pain and hepatitis C. XTL is developing Bicifadine, a serotonin and norepinephrine reuptake inhibitor, for the treatment of neuropathic pain. In addition, XTL is developing XTL-2125 - a small molecule, non-nucleoside inhibitor of the hepatitis C virus polymerase. XTL-2125 is currently in a Phase I clinical trial in patients with chronic hepatitis C. XTL is also developing XTL-6865 - a combination of two monoclonal antibodies against the hepatitis C virus. XTL's hepatitis C pipeline also includes several families of pre-clinical hepatitis C small molecule inhibitors. XTL also has an active in-licensing and acquisition program designed to identify and acquire additional drug candidates. XTL is publicly traded on the NASDAQ, London, and Tel-Aviv Stock Exchanges.

SOURCE: XTL Biopharmaceuticals Ltd.

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March 28, 2007

New HCV Treatment Recommended for Non-Responders

A new drug called Infergen is opening new doors for people infected with the Hepatitis C virus who are not responding to standard treatment. Learn why this treatment option is recommended for non-responders, and other key information to share with your physician in determining whether Infergen may be right for you.

Help for Hep C

By Margot Kim
http://abclocal.go.com

Nearly 4 million Americans are living with hepatitis C, and more than a quarter million of them have failed standard treatment options. Now, a newer, tougher drug is curing the virus in more people.

For six years, Louise Overman has battled hepatitis C -- a virus that killed the only two people she ever knew who had it. “To clear the hepatitis C was paramount to me,” she says. Her first treatment -- a yearlong ordeal -- didn't work. Her second treatment also fell short, but her goal has remained unchanged.

“Cure it. Kill the monster.”

Hepatologist Mitchell Shiffman, M.D., says that's a tough job, but it's possible. “It is the only virus that we are aware of that can actually be cured. It can be completely eradicated from the body,” he tells Ivanhoe.

But less than half of people with the most common type of hepatitis C are cured. Now, a drug called Infergen is changing the future for patients who fail standard treatment.

“Re-treatment with Infergen at a daily dose can render an additional 25 percent of these resistant patients’ virus undetectable,” Dr. Shiffman of Virginia Commonwealth University in Richmond, says. Drugs called interferons are commonly used to fight hepatitis C. Infergen is a highly potent interferon that is injected once a day for one year.

Dr. Shiffman says Infergen is FDA-approved and would likely be offered to patients who have failed previous treatments rather than given as a first treatment. That's because Infergen needs to be taken every day as opposed to once a week with other interferons.

Despite failing two different treatments, Shiffman was ready for round three. She was right. After just three months on Infergen, her virus was gone.

“That's just wonderful news. That is really amazing,” Overman says. And she says it's a relief to finally put her six-year battle behind her and get on with her life.

This article was reported by Ivanhoe.com, which offers Medical Alerts by e-mail every day of the week. To subscribe, click on: http://www.ivanhoe.com/newsalert/.

If you would like more information, please contact:

Virginia Commonwealth University Health System
Physician Referrals
(800) 762-6161

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March 19, 2007

Announcing: HCV Study to Examine Fixed Dose Induction of PEGASYS

Roche will soon test a new treatment strategy in Hepatitis C patients who have a high viral load and are overweight. Individuals with hard-to-treat characteristics will be particularly interested in the result of this trial examining the effect of combining different levels of PEGASYS and ribavirin.

http://home.businesswire.com

Roche Driving PROGRESS in Treatment of Hepatitis C Patients with New PEGASYS® Trial

Large study examines fixed dose induction of PEGASYS in patients with difficult to treat characteristics

NUTLEY, N.J.--(BUSINESS WIRE)--Roche today announced the start of a large, multinational trial to examine a new treatment strategy in hepatitis C patients with difficult-to-treat characteristics. This study will evaluate the effect of PEGASYS® (peginterferon alfa-2a) and ribavirin in patients who have a high level of genotype 1 virus in their blood (high viral load) and who are heavier than average in weight. The trial, known as PROGRESS (PEGASYS and Ribavirin Optimized in Genotype 1 high virRal load patiEntS to improve SVR), will examine the potential benefits of using a fixed dose induction (360 mcg) of PEGASYS for the first 12 weeks of therapy.

“We have seen major advances in treatment success rates for hepatitis C in recent years,” said Dr. Rajender Reddy, University of Pennsylvania and one of the lead study investigators. “However, patients with high levels of genotype 1 virus in their blood and who also are overweight tend not to respond as well to current antiviral therapy regimens. PROGRESS will reveal whether induction dosing with PEGASYS in combination with either a higher dose or a standard dose of ribavirin offers these patients an improved chance of treatment success.”

About the PROGRESS Trial

More than 1,000 patients will be enrolled in PROGRESS and will be randomized to receive one of four dosing regimens of PEGASYS plus ribavirin for 48 weeks, followed by a 24-week treatment-free follow-up period. The four dosing regimens are:

* A fixed-dose induction (360 mcg) of PEGASYS given once every week for the first 12 weeks then the standard 180 mcg dose of PEGASYS for the following 36 weeks. Patients will also receive a 1,400-1,600 mg daily ribavirin dose for the full 48 week treatment period.
* A fixed-dose induction (360 mcg) of PEGASYS given once every week for the first 12 weeks then the standard 180 mcg dose of PEGASYS for the following 36 weeks. Patients will also receive the standard dose of ribavirin (1,000-1,200 mg daily) for the full 48 week treatment period.
* The standard 180 mcg dose of PEGASYS for 48 weeks plus a 1,400-1,600 mg daily ribavirin dose for the full 48 week treatment period.
* Control group who will receive the standard of care with weekly 180 mcg PEGASYS dose plus ribavirin (1,000-1,200 mg daily) for the full 48 week treatment period.

Large Multinational Clinical Trial

Fifteen countries will participate in the trial with a total of 150 trial sites. Enrollment is ongoing in the U.S., and well as Belgium, Brazil, Canada, Denmark, Finland, France, Germany, Hungary, Norway, Poland, Romania, Russia, Sweden and the United Kingdom. The trial is expected to conclude in 2008.

“Roche recognizes that there is an urgent need to improve the chances of patients with difficult-to-treat characteristics to achieve treatment success, which is why we are launching PROGRESS,” said Tom Klein, Vice President, Hepatology, Roche. “This new, landmark trial with PEGASYS underscores our long-term commitment to finding treatment solutions for as many patients as possible.”

Previous studies have suggested that induction doses of PEGASYS, together with higher doses of ribavirin, may be of value in improving outcomes in patients with heavier than average bodyweight, genotype 1 hepatitis C and a high viral load. PROGRESS also will assess the critical and evolving role of ribavirin in optimizing treatment for patients with hepatitis C.

Those interested in the trial can find more information at www.roche-trials.com.

About Hepatitis C

Hepatitis C, a blood-borne infectious disease of the liver, is transmitted through body fluids, primarily blood or blood products, and by sharing needles. Hepatitis C chronically infects an estimated 2.7 million Americans and 170 million people worldwide and is the leading cause of cirrhosis and liver cancer and the number one reason for liver transplants in the U.S.

About PEGASYS

PEGASYS, in combination with COPEGUS (ribavirin), is indicated for the treatment of adults with chronic hepatitis C who have compensated liver disease and have not previously been treated with interferon alpha. Efficacy has been demonstrated in patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A) and patients with HIV disease that are clinically stable (e.g., antiretroviral therapy not required or receiving stable antiretroviral therapy). In addition, PEGASYS in combination with COPEGUS is the first and only FDA-approved regimen for the treatment of chronic hepatitis C in patients coinfected with hepatitis C and HIV. PEGASYS is the only pegylated interferon indicated for the treatment of adult patients with chronic hepatitis B (HBeAg positive and HbeAg negative chronic hepatitis B who have compensated liver disease and evidence of viral replication and liver inflammation).

PEGASYS is dosed at 180mcg as a subcutaneous injection taken once a week. COPEGUS is available as a 200mg tablet, and is administered orally two times a day as a split dose. Roche has backed PEGASYS with the most extensive clinical research program ever undertaken in hepatitis C, with major studies initiated to advance treatment for hepatitis C patients with unmet needs, including patients co-infected with HIV and HCV, African Americans, patients with cirrhosis, and patients who have failed to respond to previous therapy.

Important Safety Information about PEGASYS

What is PEGASYS?

PEGASYS is a medicine used to treat some adults who have hepatitis C or hepatitis B and signs of liver damage. PEGASYS works to reduce the amount of virus in your blood, helping your body fight the virus.

PEGASYS (Peginterferon alfa-2a), like other alpha interferons, can cause fatal or make life-threatening problems worse (like mental, immune system, heart, liver, lung, intestinal and infections). Your doctor should monitor you during regular visits. If you show signs or symptoms of these conditions, your doctor may stop your medication. In most patients, these conditions get better after you stop taking PEGASYS (see medication guide for more information and warnings).

What is COPEGUS?

COPEGUS is a medicine that works by slowing down the growth of the virus. COPEGUS should be taken with PEGASYS to fight the virus. Do not take COPEGUS by itself.

COPEGUS (Ribavirin, USP) can be extremely harmful and cause birth defects in an unborn baby. Female patients and the female partners of male patients should avoid getting pregnant. Ribavirin is known to cause anemia (low red blood cells), which can make heart disease worse. Also, Ribavirin can harm your DNA and possibly cause cancer (see medication guide for more information and warnings).

Who should not take PEGASYS and COPEGUS?

Do not take PEGASYS alone or with COPEGUS if:

* You are pregnant or your partner is pregnant
* You or your partner plans to get pregnant during therapy or within 6 months after treatment ends
* You are breastfeeding
* You have hepatitis caused by your immune system (autoimmune hepatitis)
* You have unstable or severe liver disease before or during treatment
* You are allergic to alpha interferons or any of the ingredients in PEGASYS and COPEGUS
* You have abnormal red blood cells (caused by conditions like sickle-cell anemia or thalassemia major)

What if I am pregnant or thinking about having a baby?

If you are a woman who could get pregnant, you must take pregnancy tests before, during and for 6 months after treatment ends to make sure you are not pregnant.

During treatment and for 6 months after treatment, female and male patients must:

* Use two forms of birth control (one being a condom with spermicide)
* Tell your doctor right away if you or your partner becomes pregnant. You or your doctor should also call the Ribavirin Pregnancy Registry at 1-800-593-2214

What medication should I avoid when I am taking PEGASYS and COPEGUS?

You should not take didanosine with COPEGUS. Talk to your doctor about all medications that you are taking.

What are the possible side effects?

The most common side effects of PEGASYS and COPEGUS are:

* Flu-like symptoms (including fever, chills, muscle aches, joint pain, headaches)
* Tiredness
* Upset stomach (like nausea, taste changes, diarrhea)
* Blood sugar problems (may lead to diabetes)
* Skin problems (like rash, dry or itchy skin, redness and swelling at injection site)
* Hair loss (temporary)
* Trouble sleeping

The most serious side effects of PEGASYS and COPEGUS are:

* Risks to pregnancies
* Mental health problems (such as irritability, depression, anxiety, aggressiveness, trouble with drug addiction or overdose, thoughts about suicide, suicide attempts, suicide and thoughts about homicide)
* Blood problems (like a drop in blood cells leading to increased risk for infections, bleeding and/or heart or circulatory problems)
* Infections (which sometimes cause death)
* Lung problems (like trouble breathing, pneumonia)
* Eye problems (like blurred vision, loss of vision)
* Autoimmune problems (such as psoriasis, thyroid problems)
* Heart problems (including chest pain and, rarely, a heart attack)
* Liver problems (rarely, liver function worsens). Patients with both the hepatitis C virus and HIV can have an increased chance of having liver failure during PEGASYS treatment. Change in a blood test that measures liver inflammation occurs more often in patients with hepatitis B. If you have a rise in this blood test you may need to be watched more closely with additional blood tests.

Tell your doctor immediately if you think you or your partner may be pregnant or if any of these symptoms occur.

About Roche

Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. pharmaceuticals headquarters of the Roche Group, one of the world’s leading research-oriented healthcare groups with core businesses in pharmaceuticals and diagnostics. For more than 100 years, the Roche Group has been committed to developing innovative products and services that address prevention, diagnosis and treatment of diseases, thus enhancing people's health and quality of life. An employer of choice, in 2006, Roche was named one of the Top 20 Employers (Science magazine), ranked the No. 1 Company to Sell For (Selling Power), and one of AARP’s Top Companies for Older Workers, and in 2005, Roche was named one of Fortune magazine’s Best Companies to Work For in America. For additional information about the U.S. pharmaceuticals business, visit our websites: http://www.rocheusa.com or www.roche.us.
Contacts

Roche
Mike Nelson, 973-562-2409
mike.nelson@roche.com
or
MS&L
Joseph St. Martin, 212-468-3731
joe.stmartin@mslpr.com

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March 12, 2007

New Dosing Study for HCV Genotype 1

Preliminary results assessing Pharmasset's R7128 treatment for Hepatitis C genotype 1 are encouraging. This well-tolerated polymerase inhibitor will now be evaluated on an ascending dose schedule. Due to current therapies for genotype 1 having a low HCV eradication rate, R7128's development is worthy of attention.

Pharmasset Initiates Multiple Ascending Dose Study of R7128 in Patients Chronically Infected With HCV Genotype 1

PR Newswire Europe (inc. UK Disclose) - Feb. 28, 2007
PRINCETON, New Jersey, February 28 /PRNewswire/ --
http://www.therapeuticsdaily.com

Pharmasset initiated the multiple ascending dose portion of an on-going Phase 1 clinical trial evaluating R7128 in up to 40 patients chronically infected with hepatitis C virus (HCV) genotype 1. The primary objective of this part of the study, being conducted in collaboration with Roche, is to assess the safety, tolerability and pharmacokinetics of multiple doses of R7128 after once-daily or twice-daily dosing for 14 days. The secondary objective is to assess antiviral efficacy of R7128 by measuring the decrease in HCV viral load. As a result of the initiation of the multiple ascending dose portion of this study, Pharmasset triggered a US$5.0 million milestone payment from Roche.

Pharmasset and Roche recently completed part 1 of this Phase 1 study in 38 healthy volunteers who received single ascending doses of R7128. The effect of food on R7128 was also assessed. Preliminary data from the single ascending dose portion of the study indicate:

- All doses of R7128 studied were generally well-tolerated.

- All patients completed the study, and none experienced gastrointestinal adverse events or serious adverse events during the study.

- No hematological or laboratory abnormalities of clinical significance were noted.

The preliminary safety and pharmacokinetic data from part 1 of the study supported progression of R7128 into part 2 of the study in patients chronically infected with HCV genotype 1.

About R7128

R7128 is a polymerase inhibitor being developed for the treatment of chronic hepatitis C. R7128 is a prodrug of PSI-6130, which demonstrated excellent potency in preclinical studies. PSI-6130 is a pyrimidine nucleoside analog inhibitor of HCV RNA polymerase, an enzyme that is necessary for hepatitis C viral replication. Results from an oral single ascending dose study in 24 healthy male volunteers showed that PSI-6130 was generally well tolerated with no serious adverse events in doses up to 3000 mg.

R7128 Phase 1 Study Overview

The Phase I clinical trial is a multiple center, observer-blinded, randomized and placebo-controlled study to investigate the pharmacokinetics, pharmacodynamics, safety, tolerability and food effect of R7128 in healthy volunteers and in patients chronically infected with HCV genotype 1. This study is comprised of two parts:

- Part 1 is a single ascending dose study being conducted in up to 38
healthy volunteers. The primary objective of Part 1 is to assess the
safety, tolerability and pharmacokinetics of R7128 following single
ascending doses under fasting conditions. The secondary objective of
Part 1 is to explore the effect of food on the pharmacokinetics of
R7128.

- Part 2 is a multiple ascending dose study being conducted in up to 40 patients chronically infected with HCV genotype 1. The primary
objective of Part 2 is to assess the safety, tolerability and
pharmacokinetics of R7128 after once-daily or twice-daily dosing for 14 days. The secondary objective is to assess antiviral efficacy by
measuring the decrease in HCV viral load.

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March 09, 2007

HIV Pathology Helps Identify Hepatitis C Protein

Rockefeller University scientists researching the HIV virus recently discovered how a protein commonly found in the liver is necessary for Hepatitis C infection. By targeting this specific protein, scientists may develop more effective treatment strategies for Hepatitis C.

http://newswire.rockefeller.edu
February 26, 2007

Key protein for hepatitis C virus entry identified

For as many as 200 million people worldwide infected with hepatitis C, a leading cause of chronic liver disease, treatment options are only partially effective. But new research by Rockefeller University scientists points to a potential new target for better drugs: a key protein that resides in human liver cells that hepatitis C requires for entry.

Scientists have known that for HCV to infect human cells, at least two molecules — CD81 and SR-B1 — must be present on the surface of the cell. However, they suspected that at least one other molecule also has to be present, because in some cells that contained the known molecules HCV was still unable to gain entry.

Co-first authors Matthew Evans and Thomas von Hahn, postdoctoral associates in Rockefeller’s Laboratory of Virology and Infectious Disease led by Charlie Rice, set out to find the missing receptor. HCV is notorious for being too difficult to replicate in cell culture, so Evans and von Hahn used HCV “pseudoparticles,” HIV particles in which the HIV envelope proteins are replaced with those from HCV. This replacement tricks the host cell into allowing the engineered particle to enter in a manner identical to that of authentic HCV. Once inside the cell, however, the HIV replication machinery takes over.

In order to identify potential entry receptors, Evans and von Hahn teamed up with co-authors Theodora Hatziioannou and Paul Bieniasz, HIV researchers at Rockefeller and the Aaron Diamond AIDS Research Center who had developed a special multiple-round screening technique. The screen pointed them to claudin-1, a protein involved in the maintenance of cell structures called tight junctions that is found in several epithelial tissues in the body, and is most prevalent in the liver.

A series of experiments on various human cell lines confirmed that claudin-1 is a requirement for HCV entry, says von Hahn. The research showed that the HCV pseudoparticle was able to enter cells that contain claudin-1, as well as claudin-1-deficient cells that were made to artificially express the protein, but not other cells. “We did not see HCV enter any cell that did not have claudin-1,” says von Hahn.

Further experiments showed that claudin-1 only appears to come into play after the virus has bound to the cell, perhaps as a means for the virion to actually be taken up by the cell or facilitate fusion between the virus and cell membranes. The scientists reported their findings this week in an advance online publication in the journal Nature.

The researchers believe that there may be additional receptors – yet to be identified – that are necessary for HCV to infect cells, as some human cell lines contain all three receptors but still do not become infected. HCV also does not enter some human cells that express all three factors, nor can it infect mouse cells that have been engineered to express the three human receptors.

The identification of claudin-1, and the possible discovery of additional host cell receptors, offers the promise of new avenues for anti-HCV therapeutics, according to the authors.

“Anti-HCV drugs currently under development are directed against viral enzymes required for viral replication, to which the virus can readily evolve resistance,” says Evans. “HCV may be less able to develop resistance to drugs targeting receptors on the host cell.”

“We also foresee the potential for combination therapies, which would attack different stages of HCV infection, much like the HIV cocktail that has been so effective,” says Rice, who is the Maurice R. and Corinne P. Greenberg Professor and scientific director of the Center for the Study of Hepatitis C, a cooperative endeavor of Rockefeller, Weill Medical College of Cornell University and NewYork-Presbyterian Hospital.

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February 20, 2007

New Approach Shifts Focus on HCV Treatment

New HCV drug treatments are now primarily focusing on inhibiting Hepatitis C viral replication by targeting a particular viral protein. Based on preliminary clinical findings, one treatment option in development has been discontinued, in favor of another lead contender as a breakthrough Hepatitis C treatment.

Gilead and Achillion Announce Positive Antiviral Activity of NS4A Antagonist in HCV, But Discontinue GS 9132 (ACH-806) Development

From the PharmaLive.com News Archive - Feb. 09, 2007

HCV Collaboration to Continue With Potential New Development Candidates

FOSTER CITY, Calif. and NEW HAVEN, Conn., Feb. 8, 2007 /PRNewswire-FirstCall/ -- Gilead Sciences (Nasdaq: GILD) and Achillion Pharmaceuticals (Nasdaq: ACHN) today announced their decision to discontinue the development of GS 9132, also known as ACH-806, for the treatment of hepatitis C viral (HCV) infection, based upon preliminary data from a Phase 1b/2 trial. Preliminary data from the first cohort of the Phase 1b/2 trial indicated that the compound demonstrated antiviral activity, validating the novel anti-HCV mechanism that involves inhibition of a viral protein called NS4A, which binds to a portion of HCV protease. However, based on small elevations of serum creatinine (a marker of kidney function), which were reversible after completion of dosing, Gilead and Achillion have elected to shift their focus to the evaluation of other NS4A antagonists developed by Achillion to identify a lead candidate for development.

"GS 9132 has demonstrated antiviral activity in patients with genotype 1 HCV infection. Even at the low dose studied, we observed significant reductions in hepatitis C viral load. This validation of the mechanism of action is encouraging as we evaluate next-generation compounds for potential development," said Norbert Bischofberger, Ph.D., Executive Vice President, Research and Development, Gilead Sciences. "We look forward to our continued collaboration with Achillion."

"As part of our collaboration with Gilead, we have worked diligently to generate a number of compounds belonging to a different chemical class that demonstrate the same mechanism of action and similar in vitro potency to GS 9132. One of the most promising of these has been designated by Achillion as ACH-1095, and we are evaluating this and other compounds in preclinical studies to determine if one has the right profile to advance into clinical development," stated Milind Deshpande, Ph.D., Chief Scientific Officer of Achillion. "Our goal is to develop a novel, efficacious and safe therapeutic for HCV, and the data indicate that candidates with this mechanism may be complementary to both protease and polymerase inhibitors, as well as interferon therapies."

The GS 9132 Phase 1b/2 trial was a double-blind, randomized, placebo-controlled dose-escalation study initiated in 2006. The goal of the trial was to evaluate the antiviral activity, safety and pharmacokinetics of GS 9132 in patients with HCV genotype 1 infection. Gilead and Achillion are continuing to analyze the data from this trial. Following completion of analysis, these data will be submitted for possible presentation at an upcoming scientific conference.

In November 2004, Gilead and Achillion established an agreement granting Gilead worldwide rights for the research, development and commercialization of certain Achillion compounds for the treatment of hepatitis C. GS 9132 and ACH-1095 are small molecule inhibitors of HCV replication, which target a viral protein called NS4A. NS4A antagonism is a novel mechanism of action for HCV treatment distinct from that of protease or polymerase inhibitors currently in development. GS 9132 and ACH-1095 were discovered by Achillion, and the company completed the initial work necessary to move GS 9132 into clinical development.

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February 06, 2007

Controlled Release Drug for Hepatitis C Being Tested

Marked by less frequent dosing, higher patient compliance and reduced side effects, OctoPlus Pharmaceuticals is now in Phase IIa testing with Locteron^TM. A controlled release version of alfa-interferon, Locteron may end up being the preferred medical treatment for Hepatitis C.

Market Wire - Jan. 30, 2007

LEIDEN, NETHERLANDS, January 30 / MARKET WIRE/ --

OctoPlus N.V. (Euronext: OCTO), the drug delivery and development company, announces today the commencement of a Phase IIa study with LocteronTM, its controlled release formulation of alfa interferon for treatment of chronic hepatitis C. The Phase IIa study is designed to evaluate Locteron in combination with the anti-viral drug ribavirin in previously untreated chronic hepatitis C patients. Recruitment of patients is ongoing and dosing has started.

Locteron is designed to be a best-in-class therapeutic for patients with chronic hepatitis C, with the potential to induce less side effects, improve patient compliance and provide a more convenient once every two week dosing schedule compared with current therapies. Results from the Phase I study, which was completed in April last year, showed that Locteron is both safe and successful in producing a gradual release over two weeks of alfa interferon after a single injection.

Locteron combines OctoPlus' proprietary PolyActive(TM) drug delivery technology with BLX-883, a recombinant alfa interferon produced by OctoPlus' co-development partner Biolex Therapeutics in its patented LEX SystemSM. Locteron is produced in OctoPlus' cGMP manufacturing facilities in Leiden, the Netherlands.

Design of the Phase IIa study

The Phase IIa study, known as SELECT-1 (Safety and Efficacy of Locteron: European Clinical Trial 1) is a European multi-center, randomized, open- label trial. SELECT-1 will evaluate a range of up to four doses of Locteron administered every two weeks in combination with ribavirin. A total of 32 treatment-naïve hepatitis C genotype I patients will receive this treatment during the 12 week study.

The study will assess viral response, safety and tolerability of Locteron. Results from this study are expected mid-2007 and will be used to select the optimal dose range to be tested in a subsequent Phase IIb study.

"The start of our lead product in its Phase IIa study is a major milestone for OctoPlus," says Joost Holthuis, CEO of OctoPlus. "We believe that Locteron has the potential to be the future treatment of choice for chronic hepatitis C, with less frequent administration and fewer side effects compared to currrent therapies."

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February 05, 2007

Announcing: New Liver Transplant Option on the Horizon

Two pharmaceutical companies are taking a similar approach in helping those facing acute liver failure. Recognizing both the ability of healthy liver cells to replicate and the difficulties involved in liver transplantation, the collaboration between Vesta and Cytonet is based on transplanting healthy liver cells to those in need.

Ex-rivals tackle acute liver disease - Vesta to produce cells for Cytonet
www.newsobserver.com
Sabine Vollmer, Staff Writer

Vesta Therapeutics, a small Durham company that is working on an alternative to liver transplants, announced Tuesday that it has gotten a contract to produce liver cells for German competitor Cytonet.

The therapies that Vesta and Cytonet are developing differ slightly. But both essentially target healthy liver cells for transplantation into patients with acute liver failure. The cells come from donated livers that were unsuitable as transplants.

Both companies hope that the contract is a step toward getting a therapy to market more quickly.

"Sometimes competitors get together and become friends," said Christian Tidona, Cytonet's head of business development.

Financial details were not disclosed.

Cytonet wants to explore whether a U.S. location makes sense, Tidona said. The deal could expand into a partnership or might even lead to Cytonet acquiring Vesta, he said.

Spun off by Swiss pharmaceutical company Roche in 2000, Cytonet is testing its therapy in humans. The company has about 50 employees.

The liver cells that Cytonet expects to receive from its contractor starting midyear will be used to determine how well Cytonet's therapy works in patients.

Development of Vesta's therapy isn't as far along. Mark Johnston, Vesta's president, said testing in patients is planned to begin this year.

Vesta is the Triangle remnant of Incara Pharmaceuticals, a once-promising Research Triangle Park company that held an initial public offering of stock in 1996. In 2002, cash-strapped Incara sold its liver cell therapy to Vesta. Incara changed its name to Aeolus Pharmaceuticals two years ago and moved its corporate headquarters to Laguna Niguel, Calif.

Since its inception, Vesta has raised more than $5 million in venture capital and research grants, Johnston said.

The contract with Cytonet provides revenue and allows Vesta to hire two lab technicians, increasing its work force to 14.

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February 02, 2007

New Virus Culture System for Hepatitis C

A new culture method greatly improves researchers' ability to study the Hepatitis C virus. Experts believe this breakthrough may enhance our knowledge of HCV, eventually contributing to enhanced treatment options.

New Culture Method For Hepatitis C Virus Uses Primary Hepatocytes And Patient Serum
medicalnewstoday.com
January 25, 2007

Researchers open the way for improved study of hepatitis C virus by devising a novel virus culture system that allows replication of patient-isolated virus in nontransformed hepatocytes, instead of culture-adapted virus strains in transformed cell lines. The related report by Lázaro et al, "Hepatitis C virus replication in transfected and serum-infected cultured human fetal hepatocytes," appears in the February issue of The American Journal of Pathology.

Hepatitis C virus (HCV) infection affects approximately 170,000,000 people worldwide. HCV liver disease, which may induce liver inflammation, cirrhosis, and/or hepatocellular carcinoma, represents the foremost reason for liver transplantation in much of the U.S.

Study of HCV replication within liver cells, or hepatocytes, has been hampered by a lack of adequate virus culture systems. Some systems allow the virus to infect cells but do not permit prolonged replication and production of virus, while other systems rely on derivatives of permissive virus isolates for efficient replication in transformed (mutated) cell lines. Still lacking has been a system to sustain replication of novel virus isolates from patients using nontransformed hepatocytes.

Nelson Fausto of the University of Washington School of Medicine has crossed this hurdle using a human fetal hepatocyte culture system that was previously developed in his lab. Using this system, his group has demonstrated sustained replication and production of virus particles for at least 2 months, with these virus particles able to infect new cells.

In their first experiments, Fausto and colleagues transfected hepatocyte cultures with HCV genomic RNA and found replication of HCV RNA genomes and production of core protein (for virus particle formation). Release of infectious virus particles was confirmed, as media from these cells were able to infect naive hepatocytes. Finally, virus particles were examined by electron microscopy and shown to possess the expected size and shape of HCV virus particles.

Once the system was established, the group examined whether sera from patients carrying HCV could infect the human fetal hepatocytes. When sera from patients infected with different HCV strains were added to the hepatocyte culture system, viral replication occurred and new virus particles were produced.

In both transfection and infection models, virus particles were released in a cyclical manner, with bursts of virus produced every 10-14 days. This is similar to what has been reported during clinical HCV infection, possibly due to the host's natural defenses. Interestingly, cultured hepatocytes responded to viral replication by displaying signs of distress and cell death and by expressing interferon-beta, a cellular antiviral, in an effort to control the infection.

This culture system provides a breakthrough in studying HCV replication in nontransformed hepatocytes, the natural target of the virus. By allowing infection by patient serum containing a wide array of virus strains, this system may allow better understanding of the differences between different strains, further improving treatment strategies.

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January 18, 2007

Announcing New Hepatitis C Treatment to Prevent Drug Resistance

A Stanford University discovery has identified certain proteins as necessary components for Hepatitis C virus replication. Presidio Pharmaceuticals has licensed the rights to use this information for developing a Hepatitis C treatment that prevents drug resistance, the leading cause of viral eradication failure.

www.endonurse.com
Presidio Pharmaceuticals Receives Exclusive License to Novel Hepatitis C Technology
January 18, 2007

SAN FRANCISCO -- Presidio Pharmaceuticals, Inc. announced today that it has licensed the exclusive worldwide rights to novel hepatitis C virus (HCV) technology from Stanford University. This technology, invented in the lab of Stanford scientist Jeffrey Glenn, targets a specific region found in the HCV proteins NS4B and NS5A, viral proteins that are absolutely required for virus replication. Disrupting the normal function of these two proteins provides for a new method of HCV treatment and should combat the emergence of drug resistance to new HCV polymerase and protease inhibitors that will be on the market in the near future.

"We are very pleased to have licensed the rights to this exciting new technology," said Omar K. Haffar, PhD, president and CEO of Presidio. "We expect to work closely with Glenn and other experts in the field to identify and test new small molecules that bind to NS4B and NS5A in order to interrupt the life cycle of the virus."

About the Hepatitis C Virus
Infections from the hepatitis C virus (HCV) have reached pandemic proportions, affecting almost 200 million people worldwide. According to the Centers for Disease Control (CDC), 3.9 million Americans have been exposed to HCV, resulting in 2.7 million cases of chronic infection, with up to 30,000 new infections occurring each year.

Source: Business Wire

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January 16, 2007

New HCV Botanical Drug Enters Clinical Trial

Utilizing Chinese medicine's long history of safe and therapeutic use, a pharmaceutical company has developed a drug derived from botanicals to treat Hepatitis C symptoms. Now that it has received FDA approval to begin clinical trials, this unique approach may become a new treatment option for Hepatitis C patients.

www.pharmalive.com
Phynova Obtains FDA Approval of its IND to Enter Into a Clinical Trial of PYN17 for the Treatment of Chronic Hepatitis C

OXFORDSHIRE, England, Jan. 8, 2007-Phynova Group PLC (AIM: PYN), a developer of pharmaceuticals derived from Chinese botanical drugs targeting viral and metabolic diseases and cancer, is pleased to announce that its first drug candidate will shortly enter into clinical trials in the US.

The Group has received approval from the US Food and Drug Administration (FDA) for an Investigational New Drug (IND) application in respect of its lead drug candidate PYN17, to proceed to the clinical trial phase. This trial will evaluate 40 patients in the USA with chronic hepatitis C (CHC).

Phynova's trial is expected to begin in Q2 2007 and will investigate the effect of PYN17 on safety and efficacy parameters. These include the key symptoms associated with CHC such as fatigue, poor concentration and abdominal pain leading to a marked deterioration in an individual's quality of life. There are no treatments currently available to effectively manage these disease symptoms.

PYN17 is a botanical drug derived from Chinese medicinal plants with a long history of safe use in humans.

Hepatitis C is a major viral disease with over 200 million sufferers worldwide including over four million in the USA.

Phynova's drug pipeline includes PYN18, an anti-viral drug for the treatment of hepatitis C and PYN22, an anti-obesity drug. In both cases patents have been filed to support these drug programmes.

Robert Miller, the CEO of Phynova said "This is a major milestone for us, validating our business model to shorten the time it takes to progress new drug candidates into human trials by developing products derived from Chinese
medicines which have a long history of use in humans. The US is the largest pharmaceutical market in the world and this approval sets us on the path to targeting that market."

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January 08, 2007

Coming Soon: More Affordable Hepatitis C Treatments

The 20-year patent on pegylated interferon is up, allowing an Indian pharmaceutical company to devise and offer an effective medication at a fraction of the cost of the current treatment. The long-time hope of HCV patients of an affordable Hepatitis C treatment may soon be realized.

Clinical trials on for low-cost hepatitis C drug
www.hindustantimes.com
Posted January 2, 2007

Treatment for hepatitis C is likely to get cheaper in the near future, with clinical trials for a new drug — called PEGylated-interferon alpha molecule — beginning in India in 2007. The new affordable drug has been developed by Dr Sunil Shaunak, professor of infectious diseases at Imperial College based at Hammersmith hospital, with scientists from Imperial College and the London School of Pharmacy.

Calling their efforts “ethical pharmaceuticals, a revolutionary new model,” Shaunk said he and his colleagues have developed a cost-effective technology that allows them open up the interferon protein, drop in a sugar molecule called PEG and close the protein. The PEGylated-interferon retains its shape and cures hepatitis C infection in many of the 170 million people affected with the disease worldwide. The new method of pegylation does not infringe existing patents because it tweaks the molecular structure of an existing drug no longer under a 20-year patent to turn it into a new medicine that can be sold much cheaper.

The efforts of Shaunak and his colleague Steve Brocchini from the London School of Pharmacy will reduce the cost of treating hepatitis C to a fraction of the current cost. It will help millions in poor countries get a cure for hepatitis C, which is a leading cause of chronic liver disease and cancer.

Hyderabad-based Shantha Biotech will manufacture the drug in India. “I have been greatly inspired by Shantha Biotech founder Varaprasad Reddy, whom I met about four years ago. The company has a record of manufacturing affordable health products. If clinical trials co-sponsored by the Indian government are successful, the new drug can be supplied the world over at an affordable price,” says Shaunak.

The new molecule, a report in the journal Nature said, appeared to be as effective as the existing drug used to treat Hepatitis C. “The aim of this work is to make affordable cures for infectious diseases for the poor people by doing most of the work in universities and hospitals using funds from charitable institutions and hospitals,” Shaunak told HT.

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January 04, 2007

Hepatitis C Immune Response Breakthrough

University of Texas researchers have recently identified the mechanism controlling the body's fight against Hepatitis C. This groundbreaking research is already being utilized to design new treatments allowing the body to clear this and other viruses.

Posted 12/29/06
Star Community Newspapers
www.carrolltonleader.com

DALLAS — Much like flipping a light switch, the hepatitis C virus turns on human immune defenses upon entering the body but also turns off those defenses by manipulating interaction of key cellular proteins, UT Southwestern Medical Center researchers have found.

This same molecular “on/off switch” controls immunity against many viruses, highlighting a potential new target for novel therapeutics to fight viruses, the researchers report.

In a study available online and in an upcoming issue of the “Proceedings of the National Academy of Sciences,” UT Southwestern scientists describe how the proteins RIG-I and LGP2 normally interact to turn on and off immune response to hepatitis C.

It’s known that when a virus invades a cell, the RIG-I protein triggers the body to generate an immune response. Once the virus has been cleared out, the LGP2 protein turns off the RIG-I signals.

This interaction between RIG-I and LGP2 is vital for properly regulating immunity, but viruses such as hepatitis C can disrupt the normal process to shut down immune defenses early, the research team found.

“This knowledge will help us design drugs that mimic the viral effects on these proteins to either activate a host’s immune response or shut it down,” said Dr. Michael Gale, associate professor of microbiology and the study’s senior author. “This holds great potential in developing new disease therapies, because the tactics employed by hepatitis C to trigger immune response are similar to those employed by other viruses such as West Nile, influenza and the common cold.”

Dr. Gale’s research centers on studying the mechanisms viruses use to evade immune defenses. Of particular interest is the hepatitis C virus, a blood-borne infection transmitted by intravenous drug use, blood transfusions and sexual contact. It affects 4 million U.S. residents and is the nation’s leading cause of cirrhosis and liver cancer.

In 2005 Dr. Gale, of Carrollton, and his team completed several breakthrough studies on hepatitis C, discovering that the RIG-I protein binds to viral genetic material. Then, RIG-I changes its shape and sends signals to other proteins that spur production of interferon, a molecule that stops viral replication. The researchers also found that the virus launches a counterattack on RIG-I, producing a protein called a protease to disrupt the signaling process, preventing interferon production and allowing viral replication.

Just how RIG-I signaling is normally regulated, however, hadn’t been known.

In the current study, UT Southwestern researchers found that RIG-I and LGP2 each contain a repressor domain, a sort of docking site that controls the actions of each protein. The domain is the key site that regulates the ability of RIG-I to bind to its signaling partners, including LGP2, acting as a switch for controlling immune response, Dr. Gale said.

“Hepatitis C and others viruses hijack this signaling pathway to stop immune defenses,” he said.

His research team and others are working to design novel therapeutics and drugs that could mimic viral effects on RIG-I to spur antiviral response or, conversely, mimic viral effects on LGP2 to shut down RIG-I activity. RIG-I shutdown would be necessary in cases when the immune system’s response to a virus is dangerously overactive, which happened in many flu cases during the 1918 pandemic.

“Fine-tuning immune response to infection is where antiviral or immune regulatory drugs are headed,” said Dr. Gale, a Nancy Cain and Jeffrey A. Marcus Scholar in Medical Research, in Honor of Dr. Bill S. Vowell.

Other UT Southwestern researchers involved in the study were microbiology postdoctoral researcher and lead author Dr. Takeshi Saito; microbiology postdoctoral researcher Dr. Yueh-Ming Loo; graduate student researchers Cynthia Johnson and David Owen; and Dr. Sangita Sinha, an instructor in internal medicine. Researchers from Kyoto University and Osaka University in Japan also were involved in the study.

The National Institutes of Health, the Burroughs Wellcome Fund and Mr. and Mrs. R. Batcheldor supported the study.

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December 27, 2006

Hepatitis C Treatment Improved with Anemia Drug

Anemia is a common side effect caused by the drugs used in Hepatitis C combination therapy. For affected individuals, researchers found that a red blood cell-boosting drug can increase tolerance for receiving full-strength Hepatitis C treatment.

Anemia Drug Helpful in Patients with Hepatitis C
December 27, 2006
paktribune.com

The hepatitis C virus can cause permanent liver damage, cancer, or even death. Early symptoms include fatigue, which can progress to the yellow staining of the skin called jaundice and swelling of the abdomen. People can get the virus through any exposure to infected blood, including intravenous drug use, body piercing, tattooing, unbandaged cuts or poorly sterilized medical equipment and blood transfusions.

Standard treatment for hepatitis C infection includes the immune system protein interferon alfa in combination with the antiviral agent ribavirin, both of which are associated with decreased hemoglobin levels, Dr. Douglas T. Dieterich and his associates note in The American Journal of Gastroenterology. When anemia results, ribavirin doses are usually reduced to levels that are likely to be less effective in controlling the hepatitis C virus.

Dieterich, from Mount Sinai School of Medicine, New York, and colleagues evaluated the efficacy of once-weekly doses of epoetin alfa in alleviating anemia and minimizing ribavirin dose reductions in 64 anemic, HCV-infected patients. After 16 weeks, patients assigned to epoetin alfa treatment had higher mean hemoglobin levels than did patients assigned to standard care, the authors report. Moreover, 83 percent of patients receiving epoetin alfa maintained daily ribavirin doses of 800 mg or more, compared with only 54 percent of patients receiving standard care.

Improvements in quality of life measures were greater in the epoetin alfa treatment group than in the standard care group, the investigators report, and epoetin alfa treatment was well tolerated.

"Based on the results of this study," the authors conclude, "epoetin alfa seems to be promising for the treatment of anemia in HCV-infected patients receiving ribavirin/interferon combination therapy. Further research is warranted to investigate the potential impact of epoetin alfa therapy on outcomes, including quality of life and sustained viral response."

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Liver Cancer Trial Yields Positive Results

Encouraging results were just announced regarding the battle on liver cancer, a devastating illness that may follow Hepatitis C infection. Recently demonstrated to decrease liver tumor recurrence by 76 percent, Progen Industries' PI-88 will progress to Phase III clinical trials for liver cancer treatment.

Positive Results For Liver Cancer Trial
December 24, 2006
www.medicalnewstoday.com

Liver cancer (or hepatocellular cancer) is the fourth most common cancer in the world and one of the most deadly, killing most patients within a year. [1] In Australia in 2002 1.3% of all male deaths were due to liver disease in (AIHW National Morbidity Database, Australia's Health 2004, AIHW).

Most cases of liver cancer are caused by hepatitis infection (usually hepatitis B or C) or cirrhosis (alcoholism being the most common cause of hepatic cirrhosis). In countries where hepatitis is not endemic, most malignant cancers in the liver are not primary liver cancer but metastasis (spread) of cancer from elsewhere in the body, e.g. the colon. Treatment options of liver cancer and prognosis are dependent on many factors but especially on tumor size and staging.

Progen Industries (ASX: PGL; Nasdaq: PGLA) today announced positive preliminary results from its Phase II clinical trial of PI-88 for the treatment of patients with primary liver cancer following surgical resection of the tumour. The trial demonstrated that PI-88 increased time to tumour recurrence by 76%.

The patient group treated with 160 mg of PI-88 had a substantial delay in tumour recurrence compared to those not receiving PI-88 (30 weeks compared with 17 weeks).

"These results are clinically very encouraging. It's hard to overstate the importance to the patient's quality of life of each day that they remain free of liver cancer. It is well known that once liver cancer recurs, the patient's survival prognosis is poor and the quality of life deteriorates dramatically," said Professor John Zalcberg, Chief Clinical Advisor to and Non-executive Director of Progen.

Justus Homburg, Chief Executive Officer of Progen stated, "We conducted this preliminary data analysis of all 168 evaluable patients at the 30-week time point to assist us now with a timely Phase 3 trial design. These results offer excellent support as we proceed to Phase 3 development, with the guidance of the FDA, as rapidly as possible. These 30-week data will not change and will be expanded upon as final 48 week data are analysed."

The final data for this Phase 2 trial (at 48 weeks -- comprising 36 weeks of treatment and a 12-week follow-up period) are expected to be available by the second quarter of 2007, once the final data from all trial sites have been checked, processed and statistically analysed. The trial is being conducted at six sites in Taiwan.

Progen is now preparing for much larger Phase III trial of PI-88 for the treatment of liver cancer which will include sites in the US, Taiwan, Singapore, China, Hong Kong and South Korea.

Dr. Chris Parish, PI-88 founding scientist from the Australian National University commented, "I am thrilled to see such strong clinical data on a product that I have spent many years studying. This demonstrates that the early discoveries we made in collaboration with Progen are now translating into benefits for cancer patients."

"The treatment of patients in a post-resection liver cancer setting is a very good match for the biological mechanism of action of PI-88. We know that even though the patient has surgery to remove the tumour there are still small tumours present. PI-88 works via a process called angiogenesis or the inhibition of growth of new blood vessels to these tumours and also on the spread of tumours, or metastatis. It is by this dual mechanism of action that we believe PI-88 has the potential to be any exciting alternative to current cancer treatments."

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December 12, 2006

Alternate HCV Combination Therapy in Phase 4 Study

Pegylated interferon and ribavirin therapy non-responders are the focus of a Phase 4 study evaluating the safety and efficacy of Infergen® (consensus interferon) in combination with ribavirin.

Valeant Pharmaceuticals International (NYSE:VRX) today announced its plans to initiate a phase 4 study of Infergen(R) (Consensus Interferon), which is in development for daily use in combination with ribavirin in the treatment of hepatitis C in patients who were non-responsive to previous pegylated interferon and ribavirin therapy. The study will evaluate the use of Infergen 15 ug/day plus ribavirin (1.0-1.2 g/day) in patients who did not have an optimal response at week 12 of treatment with pegylated interferon and ribavirin.

"Approximately 50 percent of patients do not respond to initial pegylated interferon and ribavirin therapy. Week 12 has been shown to be a pivotal time point in determining the likelihood of responding to therapy. Patients who still have detectable virus at week 12 have less chance of sustaining an SVR than those who are undetectable at week 12. These patients are in need of a new treatment regimen to improve their chance at achieving a sustained response," commented Mitchell L. Shiffman, the study's principal investigator and Chief of Hepatology at Virginia Commonwealth University Medical Center.

The multi-center, randomized U.S. study will enroll patients who received initial treatment with pegylated interferon and ribavirin and achieve a greater than 2log10 decline in HCV RNA at week 12 but still have detectable virus. The patients will be immediately randomized to receive Infergen 15 ug/day plus ribavirin (1.0-1.2 g/day) for 36 or 48 weeks or continue on their pegylated interferon and ribavirin regimen for an additional 36 weeks of therapy. All treatment groups will have a 24 week follow up period to measure sustained virologic response.

"Based on interim results from the DIRECT trial, a shorter washout period from previous pegylated interferon and ribavirin therapy and the degree of fibrosis, may affect response to daily Infergen and ribavirin. This study is the next step in the development of Infergen in patients who exhibit a poor response to initial treatment with pegylated interferon and ribavirin," said Wesley P. Wheeler, Valeant's President of North America and Global Product Development.

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December 11, 2006

Reports of New Therapy Eradicating HCV

A Brazilian case study report indicates that by adding thalidomide to standard combination therapy, six HCV-positive, prior non-responders experienced total remission of their chronic Hepatitis C. Known to cause severe congenital abnormalities, thalidomide's safety and efficacy must be investigated in future Hepatitis C trials before being considered as a viable treatment.

Report of 6 Cases of Complete HCV Remission in Prior Non-Responders Treated with Pegylated Interferon Plus Ribavirin Plus Thalidomide

By Ronald Baker, PhD
Excerpt taken from www.hivandhepatitis.com

Although it represents the current standard of care for chronic hepatitis C virus (HCV) infection, combination therapy with pegylated interferon plus ribavirin does not provide optimal treatment for this debilitating and life-threatening disease, which impacts a significant portion of the world's population.

The present article reviews a recent Brazilian paper published in Revista do Instituto de Medicina Tropical de Sao Paulo. This report describes 6 chronic HCV patients who failed initial combination therapy with pegylated interferon/ribavirin (Peg-IFN/RBV). After the addition of thalidomide to Peg-IFN/RBV therapy, all 6 experienced complete remission of their chronic hepatitis C infection and presented with negative HCV RNA, according to the author of these case reports.

The use of thalidomide in a triple combination regimen with pegylated interferon and ribavirin for the treatment of hepatitis C is described in these Brazilian case reports for the first time in the medical literature.

Source:

M M Caseiro. Treatment of chronic hepatitis C in non-responsive patients with pegylated interferon associated with ribavirin and thalidomide: report of six cases of total remission. Revista do Instituto de Medicina Tropical de Sao Paulo 48(2): 109-112. April 2006.

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December 07, 2006

New Partnership Develops Hepatitis C DNA Vaccine

DNA vaccines are the next wave of hope in disease prevention. Scheduled to make its clinical trial debut in early 2007, Inovio's proprietary electroporation DNA delivery system is designed to activate a T-cell response capable of clearing HCV.

Inovio Biomedical Partner Tripep Files Application for Phase I Clinical Study of Hepatitis C DNA Vaccine
Tuesday, December 5th

SAN DIEGO--(BUSINESS WIRE)--Inovio Biomedical Corporation (AMEX:INO), a leader in enabling the development of DNA vaccines using electroporation-based DNA delivery, announced today that its partner, Tripep AB of Sweden, has filed an application for a phase I clinical study with the Swedish Medical Products Agency. The application is designed to permit initial clinical testing of Tripep’s proprietary DNA vaccine, ChronVac-C®, administered using Inovio’s MedPulser® DNA Delivery System. This combination is designed to activate a T-cell response capable of clearing hepatitis C virus. Tripep intends to conduct a phase I clinical study in healthy volunteers at the Center for Gastroenterology at Karolinska University Hospital in Sweden beginning in early 2007.

“Our partnership with Tripep has rapidly moved this vaccine from concept to initial clinical evaluation in less than a year,” stated Avtar Dhillon, MD, Inovio’s president and CEO. “This vaccine trial represents the first study in man of an infectious disease vaccine delivered with electroporation and we are excited about the product’s potential.”

About Inovio’s DNA Delivery Technology

DNA vaccines have the potential to by-pass the numerous problems that plague conventional vaccines. For example, DNA vaccines may be better in stimulating cellular immunity necessary to fight chronic infection or diseases such as cancer. Despite this promise, vaccination using DNA plasmids alone, without enhanced delivery, has not been shown to reach the threshold for clinical benefit.

Intramuscular delivery of DNA vaccines using Inovio’s proprietary electroporation technology has been shown in primate studies to boost the immune response by orders of magnitude over DNA plasmid alone. Plasmid-based vaccines induced higher levels of antibodies and T-cell responses when delivered via electroporation, suggesting the potential to provide better protection from infectious diseases such as HIV and hepatitis C.

ChronVac-C(R) is designed to be a therapeutic DNA vaccine that can stimulate the body’s immune system. Animal experiments have demonstrated that ChronVac-C vaccination activated B-cells and T-cells (the latter being regarded as the most significant to clearing the chronic infection relating to hepatitis C) that killed cells producing HCV protein. In humans, the ChronVac-C DNA plasmid will be injected into muscle tissue, where vaccinations are usually given, and taken up by muscle cells with the assistance of Inovio’s electroporation-based DNA delivery system. These muscle cells would be expected to then produce predetermined proteins that may activate the body’s immune system to attack all cells producing HCV proteins.

Source: Inovio Biomedical Corporation

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November 24, 2006

Oglufanide Tested as Potential Hepatitis C Treatment

An Australian clinical trial is testing a novel strategy for battling Hepatitis C. Physicians are starting to treat Hepatitis C patients with oglufanide, a drug capable of regulating the body's immune response.

Drug in New Hepatitis C Clinical Trial
Tuesday November 14, 11:26 pm ET

BRISBANE, Australia, Nov. 14 /PRNewswire/ -- Physicians at Brisbane's Princess Alexandra Hospital have treated the first two patients in a clinical trial designed to test a new strategy for defeating hepatitis C viral infection, one of the toughest infectious diseases in the modern world.

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Implicit Bioscience's drug, oglufanide, which works as a regulator of the body's immune response, is being given to patients with chronic hepatitis viral infection.

"The drugs currently in use fail to control this disease in about one half of all patients," said Dr. Ian Frazer, Implicit's Chief Scientific Officer. "So there is a compelling need for new and better therapies, and we hope that oglufanide may control or reverse the suppression of the immune system which the hepatitis virus uses to defeat our normally healthy defences."

Dr. Frazer is well known as the co-inventor of the recently approved vaccine for papillomavirus which is designed to prevent cervical cancer.

Dr. Elizabeth Powell, who is the Principal Investigator for the trial which will be recruiting patients into 2007, welcomed the opportunity to study the action of oglufanide in her busy liver diseases clinic at the Princess Alexandra Hospital. "It is an important opportunity for patients to be involved in a new trial such as this, in which new treatment prospects are explored."

Oglufanide was originally developed to treat severe infectious disease in Russia (where it is a registered pharmaceutical), and was extensively studied in cancer clinical trials in the United States before being acquired by the privately-owned Brisbane biotech company Implicit Bioscience Pty Ltd in 2005. Oglufanide regulates the body's innate immune response to defeat invading germs and cancer cells. The drug is also under development by Implicit for severe respiratory diseases such as influenza (including pandemic disease) and ovarian cancer. Oglufanide has US Investigative New Drug status and Orphan Drug designation for cancer.

Source: Implicit Bioscience Inc.

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New Method for Improving HCV/HIV Co-Infection Response

Spanish researchers recently investigated the growing trend of basing ribavirin dosages on weight for those co-infected with HIV and Hepatitis C. Their results demonstrate substantial benefit to weight-dosing, and confirm the need for this individualized treatment approach.

Weight-based ribavirin dosing achieves high success rates in hepatitis C/HIV co-infected patients

Gus Cairns, Tuesday, November 21, 2006
aidsmap.com

Increasing the dose of ribavirin in interferon/ribavirin therapy and basing it on the patient’s weight can achieve impressive treatment success rates, approaching if not yet equalling those seen in HIV-uninfected patients, Spanish researchers reported last week.

Study results from the PRESCO trial of pegylated interferon and eight-based ribavirin were presented by Vincent Soriano to the Eighth Glasgow International Congress on Drug Therapy in HIV Infection in Glasgow.

PRESCO is a trial of hepatitis C (HCV) therapy in reasonably well patients: participants had to have a CD4 cell count of over 300 cells/mm3, were not allowed to take AZT (zidovudine, Retrovir) or ddI (diadosine, Videx) and were not cirrhotic. It was an open-label study, with no comparison with other regimens.

The study gave patients 180 micrograms of pegylated interferon alfa-2a (Pegasys) per week and combined it with a daily dose of either 1000mg ribavirin if the patient weighed less than 75kg or 1200mg if they weighed more.

The original PRESCO protocol, devised in December 2002, prescribed 48 weeks of treatment for patients with genotypes 1 or 4 of HCV and 24 weeks for genotypes 2 or 3. However after the APRICOT study results came out, this was amended in August 2004 to allow 72 weeks of treatment for genotypes 1 or 4 and 48 weeks for 2-3.

In the end 192 patients with genotype 1/4 took 48 weeks of treatment and 45 for 72 weeks. Ninety-six patients with genotype 2/3 took treatment for 24 weeks and 56 for 48 weeks.

Presenter Vincent Sorriano commented that it had been difficult to persuade patients to extend their treatment period and results were “hampered by voluntary withdrawal”.

The Sustained Viral Response (SVR) rates were 49.6% for all patients, 35.6% for genotype 1, 32.6% for genotype 4 and 72.4% for genotype 3 – there were virtually no genotype 2 patients in the study.

Extended treatment did convey additional benefit. SVR results for patients with genotypes 1/4 were 53% for patients who took treatment for 72 weeks and 82% for patients with genotypes 2/3 who took 48 weeks of treatment.

Hepatitis C treatment can appear to be successful, with undetectable HCV viral loads at the end of treatment, but it can then relapse and HCV can reappear, which is why the SVR is measured twelve weeks after the end of treatment and is the measure of treatment success. The relapse rate for patients with genotype 1 was 35% and with genotype 4 was 20%, with few relapsers for genotypes 2/3.

About a third (34.6%) of patients discontinued their treatment with 8.2% doing so for adverse events and 16.4% withdrawing voluntarily. About 15% of patients had their interferon dose reduced for toxicity and about 20% of patients had their ribavirin dose reduced.

The dose-limiting toxicity of ribavirin is usually anaemia. Four had to stop treatment at twelve weeks for this reason, four at 24 weeks and one at 48 weeks.

There was one death attributed to treatment in the trial – a patient who committed suicide, presumably due to the depression which is a notorious side-effect of interferon.

Sorriano contrasted his trial results with those from two previous trials: the APRICOT trial (Torriani), which is the largest study ever conducted in HIV/HCV co-infected patients but used an 800mg fixed dose of ribavirin, and the PISG trial (Fried) which used weight-based ribavirin but in monoinfected patients.

Sorriano said that PRESCO was the largest trial using weight-based ribavirin conducted in co-infected people so far and said that his results justified using this approach in future.

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November 09, 2006

Next Generation Hepatitis C Drug Begins Clinical Trial

Designed to have more anti-viral and immune-stimulating activity, Maxy-alpha is Roche's next generation interferon alpha for Hepatitis C treatment. Roche has initiated a Phase 1a study to determine the safety and efficacy of this drug.

Maxygen's Next-Generation Interferon Alpha Enters Phase 1a Clinical Trial
PR Newswire

REDWOOD CITY, Calif., Nov. 7 /PRNewswire-FirstCall/ -- Maxygen, Inc. announced today that Roche has initiated a Phase Ia clinical trial in New Zealand to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profile of Maxy-alpha, a next-generation interferon alpha for the treatment of hepatitis C virus infection.

The Phase Ia clinical trial is a double-blind, dose-escalation, controlled study of a single sub-cutaneous administration of Maxy-alpha in healthy volunteers with both placebo and PEGASYS(R) (peginterferon alfa-2a (40KD)) control groups. Maxy-alpha, also known as R7025, Roche's internal designation for the molecule, is a novel PEGylated interferon alpha variant created through the use of Maxygen's proprietary MolecularBreeding(TM) directed molecular evolution technologies. Maxy-alpha has been designed to have more anti-viral activity against the hepatitis C virus and be more effective in stimulating immune responses to help combat the infection. Preclinical data comparing Maxy-alpha to PEGASYS(R) demonstrated that Maxy-alpha has increased anti-viral and immune stimulatory activity compared to PEGASYS(R). Roche and Maxygen worked together to PEGylate Maxy-alpha to ensure comparable pharmacokinetics and dosing convenience to Roche's currently marketed PEGylated interferon alpha, PEGASYS(R).

Maxygen will receive a $2 million dollar milestone payment for the commencement of the Phase Ia trial.

"Maxy-alpha is the first 'shuffled' protein to enter clinical development," said Russell Howard, Chief Executive Officer of Maxygen. "This demonstrates how Maxygen's proprietary technologies can be used to specifically enhance desired properties of potential protein drugs. We designed this molecule to have greater potency over the currently marketed interferon alpha drugs in the hopes of addressing the large percentage of patients that are not effectively served by current therapies. We are hopeful that the forthcoming clinical trials of Maxy-alpha will demonstrate a significant improvement in the treatment of hepatitis C virus infection. Roche is an ideal partner for Maxygen's next-generation interferon alpha and we are encouraged by their enthusiasm and commitment to the program."

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October 26, 2006

Announcing a Major Breakthrough in Hepatitis C Treatment

When two separate studies produce identical results, medical innovations quickly follow. Researchers from Scripps Institute and La Jolla Institute for Allergy and Immunology have come to the same conclusion: Altering a specific immune system molecule allows a rat to successfully fight Hepatitis C. If these findings can be reproduced in humans, an entirely new way to eradicate Hepatitis C may be on the horizon.

Major Advance In Fight Against Hepatitis C And Other Chronic Virus Infections

A major finding that could lead to a new approach for treating hepatitis C and other chronic virus infections was announced today by researchers at the La Jolla Institute for Allergy & Immunology (LIAI). The research team, using controlled laboratory studies of mice, was able to eliminate a chronic virus infection in the animals by blocking a key messenger molecule in the immune system. The finding has particular relevance for hepatitis C, a viral illness which can cause liver disease and cancer, but may also be applicable to AIDS, cytomegalovirus and other chronic virus infections.

"This is a significant advance that holds great promise for the treatment of chronic virus infections," said Mitchell Kronenberg, LIAI President & Scientific Director. He noted that the research is particularly exciting because the scientific team was able to completely eradicate the usually chronic infection in the mice, not just tone it down, like many of the current treatment methods for such infections.

The research team, led by Matthias von Herrath, M.D., announced its finding in a paper, "Resolution of a Chronic Viral Infection Following IL-10 Receptor Blockade," published today in the online version of the Journal of Experimental Medicine. A separate study, led by Michael Oldstone from the Scripps Research Institute, produced similar results and was published Sunday in a science journal.

LIAI's research team used a novel method for tackling a chronic viral infection, which involved releasing the disease-fighting power of the immune system by blocking the interleukin-10 (IL-10) messenger molecule receptor with a simple antibody. Normally, this molecule, which is produced at substantial levels during hepatitis C, HIV and cytomegalovirus infections, acts to suppress the immune system's attack on chronic virus infections. "We thought, 'what if we try to correct what the immune system seems to be doing wrong in response to many chronic viral infections?,'" said von Herrath. "So we unleashed the power of the immune system by using an antibody to block the IL-10 receptor. This taught the immune system to take the right action and fight the disease."

The discovery by scientific researchers that mice chronically infected with lymphocytic choriomeningitis virus produce large amounts of IL-10 led to the development of this new intervention. Von Herrath used a version of the virus that causes chronic infections in a study involving 40 infected mice. The mice were treated with the IL-10-blocking antibody for two weeks. "They got better after one week," he said. "After two weeks, the infection was resolved in the majority of the mice and, in the end, all animals were able to cope with the virus. They developed a normal antiviral immune response, gained weight and returned to a healthy state." Von Herrath noted that their studies showed that the treatment worked best when given immediately after infection. "The later you give it after the infection, the lesser the efficacy," he said.

Von Herrath said that future studies in humans should primarily target hepatitis C because it causes the body to produce the most IL-10 of any of the chronic virus infections. Hepatitis C has been compared to a "viral time bomb." The World Health Organization estimates that about 180 million people, some 3% of the world's population, are infected with hepatitis C virus, 130 million of whom are chronic carriers at risk of developing liver cirrhosis and/or liver cancer. The hepatitis C virus is responsible for 50-76% of all liver cancer cases, and two thirds of all liver transplants in the developed world. Current estimates in the U.S. are that 3.9 million Americans are chronically infected with hepatitis C.

Currently, hepatitis C is treated with a variety of drugs, with only modest success. "The problem is you need to strengthen the immune system to fight the (chronic) virus, but in doing so it may destroy too many cells. This cellular damage can eventually become intolerable for the body," Von Herrath explained, a condition known as immunopathology. However, in their studies with IL-10, "we found that by blocking this molecule, you can release the brakes on the immune system at a crucial juncture," he said. "This results in an immune system attack that is intense enough to rid the body of the disease, but not so high as to cause immunopathology."

Von Herrath said the research team will continue to expand on the finding. "One of the next steps will be to test the IL-10 blocking antibody on human cells in the lab to see whether these cells also become normal and functional against the virus and to test combination therapies that add viral vaccines, anti-viral drugs and other antibodies to the IL-10 receptor blockade. Combination therapies bear the promise to minimize potential side effects while achieving synergy in combating the viral disease."

Source: Medical News Today

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October 20, 2006

New HCV Combination Therapy Means Fewer Sick Days

Currently in a Phase 2b clinical trial to evaluate its efficacy, safety and quality of life effects, HCV participants on Albuferon^TM with Ribavirin are showing positive results. Compared to one of the most popular treatment options available, interim trial results after 12 weeks show more favorable life markers with this new drug combination.

Source: Human Genome Sciences, Inc

Positive Interim Quality-of-Life Data From Phase 2B Trial of Albuferon(TM) With Ribavirin in Treatment-Naive Hepatitis C Patients

Albuferon associated with fewer missed work days and better patient-reported quality-of-life scores than pegylated interferon through week 12 -

ROCKVILLE, MD -- October 16, 2006 -- Human Genome Sciences, Inc. today reported 12-week interim quality-of-life results from a phase 2b clinical trial to evaluate the efficacy, safety and impact on health-related quality of life of Albuferon(TM) in combination with ribavirin in patients with genotype 1 chronic hepatitis C (HCV) who are naive to interferon alpha-based treatment regimens.

The interim results demonstrate that all Albuferon treatment groups consistently performed favorably through week 12 compared to the pegylated interferon alpha treatment group, based on patient-reported disability days and health-related quality of life as measured by the SF-36 health survey. The data were presented over this past weekend at the annual Australian Gastroenterology Week in Adelaide.

Health-related quality-of-life issues, including lost days of work and normal activity, pose a significant challenge for patients undergoing treatment for chronic hepatitis C," said Stephen Pianko, MD, FRACP, PhD, Associate Professor of Medicine, Monash University (Melbourne, Australia). "Interim results of the current study suggest that Albuferon may have the potential to offer a therapeutic alternative with less impairment of health-related quality of life, and fewer disability days, compared with the current standard of care, with at least comparable safety and efficacy. We look forward to continuing the evaluation of Albuferon to determine its appropriate role in the treatment of hepatitis C."

"Through week 12 of the phase 2b study, patients in the Albuferon treatment groups recorded fewer missed work days and, based on the SF-36 health assessment, reported better quality of life than patients in the pegylated interferon treatment group," said David C. Stump, MD, Executive Vice President, Drug Development, HGS. "This result was observed in both the physical and mental component summary measures, as well as in the 8 individual domain scores. The SF-36 results in mental health suggest significantly less impairment of psychological well-being across the Albuferon treatment groups."

About the Albuferon Phase 2B 12-Week Quality-of-Life Results
Albuferon treatment groups recorded fewer disability days and reported less impairment of health-related quality of life through week 12 of the phase 2b study than patients in the pegylated interferon treatment group. The 900- mcg Albuferon dose administered at 2-week intervals was associated with 75% fewer disability days, and the 1200-mcg Albuferon doses administered at 2-week and 4-week intervals were associated with 25% fewer disability days.

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October 19, 2006

HCV Genotype 1: Anti-viral HCV Drug Advances to Phase II

Granted fast track status, Roche's® R1626 is beginning a Phase II study to evaluate its safety and HCV anti-viral activity. Administered in combination with PEGASYS® and COPEGUS®, this trial is now enrolling people with HCV genotype 1 who have previously not received treatment.

BASEL, Switzerland, October 13
FDA Grants Fast Track Status to R1626
excerpt taken from Earthtimes.org

Roche announced today the start of the first phase II development studyto evaluate R1626, their promising new polymerase inhibitor, for the treatment of hepatitis C. The investigational drug has also been granted FastTrack status by the US Food and Drug Administration (FDA), a program designed to facilitate the development and to expedite the review of new drugs withthe potential to help treat serious or life-threatening conditions.

R1626 has been shown in an earlier study to have a strong antiviraleffect against the hepatitis C virus. In the phase I study[1] , the drug achieved significant reductions in viral load in chronic hepatitis C patients infected with the difficult-to-cure genotype 1 virus. By moving R1626 intophase II trials, Roche signifies its commitment to finding more therapeutic solutions for patients with hepatitis C. This trial will evaluate the safety and antiviral effects of R1626 in combination with the current standard of care for hepatitis C, Roche's PEGASYS (peginterferon alfa-2a (40KD)) and COPEGUS (ribavirin).

About the phase II trial

This on-going multicenter phase II trial that is enrolling patients with genotype 1 chronic hepatitis C who have not previously received treatment.

Patients are randomised into four treatment groups. These treatment groups are:

- Group A: R1626 1500mg twice a day + Pegasys 180mcg as a subcutaneous injection every week for 4 weeks

- Group B: R1626 3000mg twice a day + Pegasys 180mcg as a subcutaneous injection every week for 4 weeks

- Group C: R1626 1500mg twice a day + Pegasys 180mcg as a subcutaneous injection every week + Copegus 1000-1200mg daily for 4 weeks

- Group D: Pegasys 180mcg as a subcutaneous injection every week + Copegus 1000-1200mg daily (standard of care group) for 4 weeks

Following the first 4 weeks of treatment, all patients will receive Pegasys 180mcg subcutaneously every week + Copegus 1000-1200mg daily for another 44 weeks, making the total treatment duration of 48 weeks. The objectives of the study are to evaluate the 4 week safety and antiviral effect of combining R1626 with Pegasys alone or R1626 with Pegasys plus Copegus.

The study is currently enrolling patients in the US. Patients and healthcare providers interested in the trial can find more information at www.roche-trials.com.

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October 06, 2006

New Hepatitis C Drug Enters Phase III Trial

Nearly 1,300 people with Hepatitis C genotype 1, the most common strain in the US, will be testing a new drug in a Phase III trial. The new drug, Albuferon, will be compared with the current gold standards of HCV treatment, PEGASYS® and PEG-IFN alpha 2a.

Human Genome Sciences tests Hep C drug
United Press International

ROCKVILLE, Md., Oct. 4 (UPI) -- U.S. firm Human Genome Sciences said Wednesday it has begun a phase 3 trial of Albuferon in patients with chronic hepatitis C.

The company said it would test its albumin-interferon alpha 2b in more than 2,000 treatment-naive patients with the disease.

"We believe that Albuferon could become the best-in-class immunomodulator in treatment regimens for chronic hepatitis C, and we are pleased to move this important program forward," said H. Thomas Watkins, HGS's president and chief executive officer. "Advancing Albuferon to Phase 3 development is a major step toward the transformation of HGS into a development and commercialization company."

The phase 3 development program will compare therapy with Albuferon in combination with ribavirin, versus PEGASYS, or PEG-IFN alpha 2a, in combination with ribavirin.

The testing will consist of two separate clinical trials -- ACHIEVE 1, which will enroll at least 1,278 patients with chronic hepatitis C genotype 1 -- and ACHIEVE 2/3, which will involve a minimum of 918 subjects with chronic hepatitis C genotype 2 or 3.

The studies will assess the drug's efficacy, safety and impact on health-related quality of life.

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October 04, 2006

New HCV Combination Therapy

The current medications composing HCV combination therapy are being challenged by Valeant Pharmaceuticals. A recent study reported that HCV therapy with interferon and Viramidine® has fewer side effects than today's standard combination therapy.

Valeant Pharmaceuticals Reports VISER2 Results for Viramidine®
Company Initiates Phase 2b Weight-Based Dose-Ranging Study

COSTA MESA, Calif., September 12, 2006 – Valeant Pharmaceuticals International (NYSE: VRX) today reported summary results of VISER2, the second of two Phase 3 pivotal trials, for Viramidine®. The company is developing Viramidine (taribavirin hydrochloride), a nucleoside (guanosine) analog prodrug of ribavirin, in oral form, for administration in combination with a pegylated interferon for the treatment of chronic hepatitis C in treatment-naïve patients. The VISER2 trial included two co-primary endpoints: one for safety (superiority to ribavirin in the incidence of anemia) and one for efficacy (non-inferiority to ribavirin in sustained viral response, SVR).

The VISER2 study did not meet the non-inferiority efficacy endpoint on an intent-to-treat (ITT) basis, with overall SVR rates of 40 percent versus 55 percent for the Viramidine and ribavirin arms, respectively. However, consistent with the results seen in VISER1, SVR rates in VISER2 trended higher among patients receiving increased exposure on a mg/kg basis in the Viramidine arm without a substantial increase in the anemia rate.

Consistent with results from the VISER1 trial released earlier in the year, VISER2 confirmed the safety advantages of Viramidine. Anemia rates (Hgb < 10g/dL) during the treatment period were significantly lower in patients treated with Viramidine than those treated with ribavirin (6 percent versus 22 percent; p<0.001).

As a result of the combined VISER1 and VISER2 data, the company also announced that it is initiating a Phase 2b program to evaluate the efficacy of Viramidine at higher doses. The Phase 2b program is a multi-center, randomized, parallel, open-label study in 240 treatment naïve, genotype-one patients and will evaluate Viramidine at 20 mg/kg, 25 mg/kg, and 30 mg/kg per day in combination with pegylated interferon alpha-2b. There also will be a control group comprised of ribavirin and pegylated interferon alpha-2b. Treatment duration will be 48 weeks with a post-treatment follow-up period of 24 weeks. Based on a 12-week interim analysis of this study, the company will decide whether to begin a third Phase 3 study at the appropriate higher dose indicated by the Phase 2b study. The company will seek to co-develop the product should it decide to pursue another phase 3 registration trial next year.

Timothy C. Tyson, president and chief executive officer, said, “As expected, VISER2 results were consistent with those seen in VISER1. Although VISER1 and 2 did not meet non-inferiority efficacy endpoints, Viramidine demonstrates meaningful clinical efficacy. Our retrospective analyses of 750 patient plasma samples indicate that Viramidine could be as effective as ribavirin at higher doses. These analyses, coupled with feedback from the medical community that there will continue to be a strong need for ribavirin or ribavirin analogues in the treatment of hepatitis C, indicate that further clinical testing is prudent. Our Phase 2b program should provide us with sufficient information at little relative cost and time to confirm the dose response, select an appropriate dose, test safety at higher doses, establish the path for registration of the drug and make a go/ no-go decision .”

The company also announced the issuance of a U.S. patent for Viramidine for use in the treatment of hepatitis C, which will not expire until 2020.

The majority of adverse events other than anemia and gastrointestinal side effects were similar between treatment groups. The anemia rate was lower in the Viramidine arm, while the gastrointestinal rate was lower in the ribavirin arm. The most common other adverse events associated with combination therapy included fatigue, headache, insomnia, depression and myalgia.

VISER2 Trial Design

The VISER2 trial (VISER stands for VIramidine’s Safety and Efficacy vs. Ribavirin) evaluated a fixed 600 mg BID dose of Viramidine to a weight-based 1,000/1,200 mg daily dose of ribavirin, both in combination with peginterferon alfa 2a. The study, conducted in the United States, Canada, Europe, Israel, Argentina and Australia , enrolled 962 treatment-naïve subjects with chronic HCV. Treatment duration was based on genotype, with genotypes 2 and 3 receiving 24 weeks of treatment and genotype non 2, 3 receiving 48 weeks of treatment, each with a post-treatment follow-up period of 24 weeks. The study was stratified for genotype, weight and viral load.

Additional information regarding the Phase 3 trial will be furnished by the company today with the Securities and Exchange Commission on Form 8-K and is also available on the company’s Web site at www.valeant.com.

Viramidine is an investigational compound that has not been found by the Food and Drug Administration (FDA) or any other regulatory agency to be safe or effective in the diagnosis, mitigation, treatment or cure of any disease or illness. It may not be sold or promoted in the United States unless and until FDA has approved a New Drug Application. Similar restrictions apply in other countries.

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September 28, 2006

Discovery May Prompt New HCV Treatments

Scientists have discovered a protein necessary for liver cell regeneration, an ability that is directly impacted by liver disease. The identification of this protein in helping the liver to heal itself opens up a new realm of liver disease treatment possibilities.

Regenerating Hope For Liver Disease, University Of Queensland
Medical News Today
September 15, 2006

A protein essential in the process of liver regeneration has been identified by a team of scientists in a discovery that could lead to treatments for serious liver diseases such as hepatitis.

The protein, caveolin-1, was identified as being necessary for regeneration by a team of scientists from the Institute for Molecular Bioscience at The University of Queensland, and the University of Barcelona.

“The liver has an amazing capacity to regenerate and repair itself after damage, such as a heavy session of drinking,” Professor Robert Parton, one of the team leaders, said.

“But in some diseases, such as hepatitis and cirrhosis, the liver is so damaged that it loses this regeneration capacity.

“Identifying that caveolin-1 is an essential ingredient in the process of liver regeneration brings us a step closer to finding treatments for people whose livers are not able to heal themselves.”

The team members made their discovery by comparing normal mice with mice that were unable to produce caveolin-1.

The livers of the vast majority of normal mice were able to regenerate after damage, while three-quarters of the mice without caveolin-1 died if they sustained significant liver damage.

“The livers of mice that couldn't produce caveolin-1 were not significantly different to normal mice before any damage occurred,” Professor Parton said.

“This suggests that other proteins may compensate for the lack of caveolin-1 when the liver is functioning normally, with its essential role becoming apparent only when the liver is injured.”

The team's findings have been published in the current edition of top international journal Science, on the eve of UQ's Research Week.

Research Week celebrates the outstanding research that is produced at The University of Queensland with public forums, seminars, workshops and the annual UQ Foundation Research Excellence Awards.

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September 15, 2006

MRI Breakthrough for Liver Diagnosis

Magnetic Resonance Imaging (MRI) technology can now help detect end stage liver disease. Needle biopsies will quickly become archaic as this painless, low-risk and accurate method continues to demonstrate promise in evaluating liver fibrosis.

Mayo Clinic in Rochester

Thursday, September 07, 2006

Liver Diagnosis Breakthrough with Mayo Clinic MRI Development
MR Elastography provides early warning

Mayo Clinic researchers have developed a new technique for using magnetic resonance imaging (MRI) to accurately measure the hardness or elasticity of the liver. First tests show this technology -- called MR Elastography (MRE) -- holds great promise for detecting liver fibrosis, a common condition that can lead to incurable cirrhosis if not treated in time. Traditionally, liver fibrosis is usually diagnosed using needle biopsies, which can involve complications and may be inaccurate due to sampling errors. The new technology promises to provide an accurate, painless, and lower risk alternative to liver biopsy and may have implications for diagnosing cancer. These research findings appeared in the journal Radiology.

"This is potentially an important diagnostic advance, since conventional imaging techniques, such as CT, MRI and ultrasound are not capable of identifying liver fibrosis prior to the onset of cirrhosis," says Richard Ehman, M.D., Mayo researcher and lead investigator on the study.

"The Elastogram"

The healthy liver is very soft compared to most other tissues and especially compared to a liver with cirrhosis, which is rock hard. The development by Dr. Ehman and his colleagues applies vibrations to the liver and then utilizes a modified form of MRI to obtain pictures of the mechanical waves passing through the organ. The imaging can be accomplished in as little as 20 seconds. The wave pictures are then processed to generate a quantitative image of tissue stiffness -- called an elastogram.

Researchers compared results of the process on 12 patients with biopsy-proven liver fibrosis with those of 12 healthy participants. This pilot trial of MRE showed strikingly elevated stiffness in patients with fibrosis and that the stiffness increased with the progression of the condition.

Impact of the Research

The availability of a reliable, non-invasive method for detecting liver fibrosis could lead to early diagnosis -- in patients considered at risk for liver disease -- and increase their chances for successful treatment. For example, 170 million people worldwide are infected with chronic hepatitis C and a significant number will develop cirrhosis, which is untreatable. Even if some risk factors are identified, there is no way to predict which patients will develop fibrosis, and successive liver biopsies in all these patients aren't possible. Non-invasive monitoring with MRE of those at risk would detect the problem early and help assess the effect of treatments.

Collaboration and Support

Others on the research team include Meng Yin; Olivier Rouviere, M.D.; Jayant Talwalkar, M.D.; M. Alex Dresner, Ph.D.; Phillip Rossman; Lawrence Burgart, M.D.; and Jeff Fidler, M.D. The research was funded in part by the National Institutes of Health.
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September 14, 2006

Oral Medication Lowers HCV Viral Load

Results of a Phase II study indicate that the oral medication Suvus (TM) can significantly lower HCV viral load without any major side effects. Because it was only tested to battle HCV genotype 4a, this medication may not directly benefit those with other HCV genotypes. However, hope lies in the fact that progress is being made against the virus as a whole, with new breakthroughs occurring every day.

Bioenvision's Suvus(TM) Lowers Viral Load in Chronic Hepatitis C; Randomized Study Data Presented at Scientific Conference

Bioenvision, Inc. (NasdaqGM:BIVN) today announced results of a randomized Phase II trial of Suvus(TM) in patients with chronic hepatitis C virus infection (HCV). The data was presented at the British Association for the Study of the Liver's annual meeting in Dublin.

The study assessed the safety, tolerability and efficacy of Suvus(TM) in patients with chronic HCV genotype 4a infection. Patients were randomized to receive Suvus(TM) orally 60 mg twice daily for either 50 days or 100 days of treatment. In patients receiving 50 days of Suvus(TM) treatment the median viral load fell from a pre-treatment level of 7.3x10(6)/ml to 1.4x10(6)/ml, with a mean percentage decrease of 83%. In patients receiving 100 days of Suvus(TM) treatment the median viral load fell from a pre-treatment level of 6.0x10(6)/ml to 0.53x10(6)/ml, with a mean percentage decrease of 92%. Suvus(TM) was well tolerated, and slight discoloration of the feces was the only reported side-effect.

"We are excited to see critically ill patients with HCV responding so well to Suvus(TM). The results are particularly significant when you consider most of the patients had failed prior therapy and had cirrhosis of the liver," said Professor Habib, the lead investigator of the study.

These results confirm those of a previous investigator sponsored Phase II study in which Suvus(TM) achieved significant reduction in viral load in patients with refractory HCV infection.

"We want to make Suvus(TM) available first in countries where HCV has a high prevalence and where cost-effective treatment options are essential," said Dr. Christopher B. Wood, Chairman and Chief Executive Officer of Bioenvision.

Bioenvision has filed for marketing authorization in Egypt. An estimated 7-8-million people in Egypt are infected with hepatitis C and most (90%) have genotype 4a. The World Health Organization estimates approximately 3-percent of the world's population (approximately 170-200-million people) are infected with HCV.

SOURCE: Genetic Engineering News

CONTACT: Bioenvision, Inc. Investors: David P. Luci, Esq., 212-750-6700 davidluci@bioenvision.com or Media: Hugh S. Griffith, + 44 (0) 131 248 3555 hughgriffith@bioenvision.com or Mary Ann Ondish, 212-750-6700 maryannondish@bioenvision.com

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September 01, 2006

Discovery of Gene Gives HCV Patients Hope

Researchers have uncovered a gene capable of preventing HCV replication. With modern technology's ability to use genetic microbiology in the fight against disease, this discovery could lead to viable treatment developments for Hepatitis C.

Media Release
Wednesday 9 August, 2006
New hope for hepatitis C research

The mystery surrounding Hepatitis C, a disease that affects millions of people worldwide, is one step closer to being solved.

In a paper published in the August edition of Journal of Virology, scientists describe how they replicated,or reproduced the hepatitis C virus (HCV) in mouse cells. Working with different models, they showed a gene called protein kinase R (PKR) blocked the replication of HCV in mice.

“When a person becomes infected with HCV, the immune system produces a protein called interferon to fight the infection,” said co-author and Director of the Monash Institute of Medical Research, Professor Bryan Williams. “We now know genes interferon stimulates PKR to try to stop the virus spreading throughout the body.”

HCV replicates at a very high rate – approximately one trillion viral particles are produced each day in an infected person. Professor Williams’ research will provide a better understanding of how this replication occurs and how and why PKR blocks the production of the virus.

Hepatitis C affects 210,000 Australians. Worldwide, it is estimated more than 170 million people suffer from the disease1. The virus attacks the liver, causing flu-like symptoms, fevers, abdominal pain, depression, and for two-thirds of patients, chronic liver disease.

The discovery may also shed light on why some hepatitis C patients respond better to treatment than others.

“As there is no vaccine or cure for HCV, the only treatment on offer for patients is interferon therapy,which aims to slow the progression of the disease. However, there are six different genotypes, or strains of HCV, which all react differently to treatment,” Professor Williams said. “We can now explore why some strains are more sensitive to interferon therapy, and how we can adapt treatment to the different strains of the disease.”

“Our research is still in the early stages, but the research model we have created will be a valuable tool in understanding the underlying mechanisms of chronic HCV infection, and how the virus responds to interferon treatment” said Professor Williams.

Research collaborators were the Monash Institute of Medical Research, the Department of Microbiology,Immunology and Molecular Genetics, University of Kentucky College of Medicine, Kentucky, USA and the Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, USA.

A full copy of the research paper is available at: http://jvi.asm.org/current.dtl#VIRUS_CELL_INTERACTIONS
1. Hepatitis C Council of Victoria: www.hepcvic.org.au
More information / interview opportunities:
Contact Julie Jacobs, Public Relations Manager: (+613) 9594 7109 or 0408 135 256.

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August 31, 2006

New Hepatitis C Treatment Being Unveiled

A novel approach to hepatitis C treatment will be presented at this year's annual meeting of the American Association of Liver Diseases. The preliminary results for a new class of drug designed to destroy both HCV viral particles and HCV infected cells show great promise. Bavituximab's recognition at this high-profile and well-respected event signifies this drug's potential.

Peregrine's Final HCV Phase 1a Study Results Accepted for Oral Presentation at AASLD Annual Meeting

- Study Results for First-in-Class Agent Bavituximab Will Be Presented at The Liver Meeting(R), the Leading Scientific Meeting on Liver Disease -

TUSTIN, Calif., Aug. 16 /PRNewswire-FirstCall/ -- Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM), a biopharmaceutical company with a portfolio of innovative, clinical stage products for the treatment of hepatitis C virus (HCV) infection and cancer, today announced that data from its Phase la study of bavituximab in patients with chronic hepatitis C viral (HCV) infection have been accepted for oral presentation at The Liver Meeting(R) 2006, the premier event in the science and practice of hepatology hosted by the American Association for the Study of Liver Diseases (AASLD).

"We believe that bavituximab represents a potentially valuable new approach for the treatment of chronic HCV infection. Given the novel nature of this approach, we are very pleased that AASLD has selected our clinical data for an oral presentation," said Steven W. King, president and CEO of Peregrine. "The next phase of the HCV clinical program is already underway with patient enrollment in the Phase 1b repeat dose study proceeding well and on track for completion by year-end. The presentation at The Liver Meeting gives us an excellent opportunity to raise awareness of the potential promise of the bavituximab HCV program as we continue clinical development."

Over 5,000 hepatologists and hepatology health professionals from around the world will meet at the 57th Annual Meeting & Postgraduate Course of AASLD -- The Liver Meeting at the John B. Hynes Convention Center in Boston, Massachusetts from October 27-31, 2006. The bavituximab presentation is scheduled for October 30, 2006 at 3:00 pm EST.

About Bavituximab

Bavituximab is the first investigational agent in a new class of anti-phosphatidylserine (anti-PS) immunotherapeutics that targets and binds to cellular components not normally present on the outside of cells, but which become exposed on certain virally infected cells and on the surface of enveloped viruses. Bavituximab helps stimulate the body's immune defenses to destroy both the virus particles and the infected cells. Bavituximab is currently in clinical trials for the treatment of chronic hepatitis C virus infection. Preliminary results from an ascending single dose Phase la trial in HCV patients reported earlier this year indicated that bavituximab was well tolerated, and it showed promising signs of anti-viral activity. A repeat dose Phase 1b HCV trial is ongoing and is expected to be completed by year-end. Similar to their proposed anti-viral mechanism, anti-PS immunotherapeutics also bind to phospholipids exposed on tumor blood vessels in all solid cancers tested to date. Bavituximab is currently in Phase 1 clinical trials for the treatment of advanced refractory solid tumor cancers.

About Peregrine Pharmaceuticals

Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative product candidates in clinical trials for the treatment of cancer and hepatitis C virus (HCV) infection. The company is pursuing three separate clinical trials in cancer and HCV infection with its lead product candidate bavituximab (formerly Tarvacin) and Cotara(R). Peregrine also has in-house manufacturing capabilities through its wholly owned subsidiary Avid Bioservices, Inc. (www.avidbio.com), which provides development and bio-manufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at www.peregrineinc.com.

Safe Harbor Statement: Statements in this press release which are not purely historical, including statements regarding Peregrine Pharmaceuticals' intentions, hopes, beliefs, expectations, representations, projections, plans or predictions of the future are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The forward-looking statements involve risks and uncertainties including, but not limited to, the risk that bavituximab's safety profile in a repeat dose trial or in a combination therapy trial will not be at the same safety level as was found in the Phase 1a trial, the risk that the results of future trials will not correlate to the results from the Phase 1a trial, and the risk that bavituximab will not be as well tolerated at ascending doses. It is important to note that the company's actual results could differ materially from those in any such forward-looking statements. Factors that could cause actual results to differ materially include, but are not limited to, uncertainties associated with completing preclinical and clinical trials for our technologies; the early stage of product development; the significant costs to develop our products as all of our products are currently in development, preclinical studies or clinical trials; obtaining additional financing to support our operations and the development of our products; obtaining regulatory approval for our technologies; anticipated timing of regulatory filings and the potential success in gaining regulatory approval and complying with governmental regulations applicable to our business. Our business could be affected by a number of other factors, including the risk factors listed from time to time in the Company's SEC reports including, but not limited to, the annual report on Form 10-K for the year ended April 30, 2006. The Company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. Peregrine Pharmaceuticals, Inc. disclaims any obligation, and does not undertake to update or revise any forward-looking statements in this press release.

SOURCE Peregrine Pharmaceuticals, Inc.

/CONTACT: Barbara Lindheim, +1-212-918-4949, ir@peregrineinc.com; or Media, Stephen Gendel, +1-212-918-4650, both of GendeLLindheim BioCom Partners, for Peregrine Pharmaceuticals, Inc.

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August 30, 2006

Delivery System Stimulates HCV Immunity

Two companies committed to finding a vaccine for hepatitis C have released encouraging news on their progress. Tripep and Inovio's efforts to introduce a genetically engineered medicine through a patented DNA delivery system appear to stimulate immunity against Hepatitis C. As it evolves, this technology represents great hope for controlling the spread of the Hepatitis C virus.

Tripep Produces Additional Positive Data for Its Hepatitis C DNA Vaccine Using Inovio's DNA Delivery System

SAN DIEGO--(BUSINESS WIRE)--Aug. 28, 2006--Inovio Biomedical Corporation (AMEX:INO) announced today that its partner, Tripep AB of Sweden, has achieved additional positive pre-clinical results showing that its ChronVac-C DNA vaccine combined with Inovio's MedPulser® DNA delivery system produced a strong immune response against hepatitis C virus (HCV) in a large animal model. Ongoing toxicity studies of ChronVac-C® delivered using Inovio's electroporation-based system revealed that the combination induces a humoral response in rabbits that is comparable to results previously observed in mice.

"These results provide encouragement that the combination of ChronVac-C with the MedPulser DNA delivery system may work well in humans and indicate that our collaboration with Inovio is progressing very well," said Tripep's CEO, Jan Nilsson.

"We are pleased to see continuing positive data from this program and Tripep's ongoing commitment to the development of this DNA vaccine with the goal of initiating a clinical study using Inovio's MedPulser® DNA delivery system," stated Avtar Dhillon, MD, Inovio's president and CEO.

About Hepatitis C and ChronVac-C

Hepatitis is a disease characterized by inflammation of the liver. Hepatitis C virus (HCV) is a major cause of acute hepatitis. HCV is spread primarily by direct contact with human blood, the major causes worldwide being the use of unscreened blood transfusions, and re-use of needles and syringes that have not been adequately sterilized. As many as 70% - 90% of newly infected patients may progress to develop chronic infection (WHO: 2002). Of those with chronic liver disease, 5% - 20% may develop cirrhosis. About 5% of infected persons may die from the consequences of long term infection (due to liver cancer or cirrhosis). Globally, an estimated 170 million people are chronically infected with HCV, which represents a reservoir sufficiently large for HCV to persist, and 3 to 4 million persons are newly infected each year. In the US, while new incidences of HCV have dropped dramatically, an estimated 4.1 million (1.6%) Americans have been infected with HCV, of whom 3.2 million are chronically infected (Centers for Disease Control and Prevention: 2006).

HCV infections in the liver do not trigger an immune response very effectively. Certain antiviral therapies, while expensive, are somewhat effective in treating hepatitis C, but there is no vaccine currently available to prevent hepatitis C. ChronVac-C® is designed to be a therapeutic DNA vaccine that can stimulate the body's immune system. Animal experiments have demonstrated that ChronVac-C vaccination activates B cells and T-cells (the latter being regarded as the most significant to clearing the chronic infection relating to hepatitis C) that killed cells producing HCV protein. In humans, the ChronVac-C DNA plasmid would be injected into muscle tissue, where vaccinations are usually given, and taken up by muscle cells with the assistance of Inovio's electroporation-based DNA delivery system. These muscle cells would be expected to then produce predetermined proteins that may activate the body's immune system to attack all cells producing HCV proteins.

About Tripep AB

Tripep AB is a Swedish biotechnology research company that develops and commercialises candidate drugs based on patented and proprietary technologies. Its main focuses are research and clinical development of ChronVac-C®, a therapeutic vaccine against hepatitis C; preclinical research focusing on the development of the therapeutic and prophylactic vaccines against influenza A and HIV; the RAS® technology platform. More information is available at www.tripep.se or contact Jan Nilsson, CEO at +46 8 449 8480 or jan.nilsson@tripep.se.

About Inovio Biomedical Corporation

Inovio Biomedical Corporation is a late stage biomedical company focused on commercializing its proprietary Selective Electrochemical Tumor Ablation (SECTA) therapy. SECTA is designed to target a significant unmet clinical need: a local treatment for solid tumors, with selective killing of cancer cells while preserving surrounding healthy tissue. Inovio is moving its lead product, the MedPulser®, through pre-marketing studies for head and neck cancer and skin cancers in Europe, where it has CE Mark accreditation, a U.S. Phase III pivotal study for head and neck cancer, and Phase I trials for pancreatic and breast cancer. Merck, Vical, University of Southampton, and H. Lee Moffitt Cancer Center are using Inovio's gene delivery technology in clinical studies of novel DNA therapeutics delivered using electroporation. Inovio is a leader in developing human therapeutic applications of electroporation, with the industry's most extensive patent portfolio covering in vivo electroporation. More information is available at www.inovio.com.

This press release contains certain forward-looking statements relating to our plans to develop our electroporation drug and gene delivery technology. Actual events or results may differ from our expectations as a result of a number of factors, including the uncertainties inherent in clinical trials and product development programs (including, but not limited to, the fact that pre-clinical results referenced in this release may not be indicative of results achievable from testing in humans), the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of Inovio's technology as a delivery mechanism, the availability or potential availability of alternative therapies or treatments for the conditions targeted by Inovio or its collaborators, including alternatives that may be more efficacious or cost-effective than any therapy or treatment that Inovio and its collaborators hope to develop, evaluation of potential opportunities, issues involving patents and whether they or licenses to them will provide Inovio with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether Inovio can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of our technology by potential corporate or other partners or collaborators, capital market conditions, and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2005, our Form 10-Q for the six months ended June 30, 2006, and other regulatory filings. There can be no assurance that any product in our product pipeline will be successfully developed or manufactured, or that final results of clinical studies will be supportive of regulatory approvals required to market licensed products.

CONTACT: Inovio Biomedical Corporation
Bernie Hertel, 858-410-3101 (Investor Relations)
or
Porter Novelli Life Sciences
Susan Neath, 858-527-3486 (Media Relations)

SOURCE: Inovio Biomedical Corporation

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August 18, 2006

New Test Identifies HIV/HCV Co-Infection

One-third of all HIV positive patients are also infected with the hepatitis C virus. A new diagnostic test allows physicians to quickly identify both viruses with a single blood sample. With this diagnostic tool, doctors can immediately begin tailoring a comprehensive treatment plan.

MedMira Offers New Rapid Diagnostic to Combat “the hidden epidemic” - Co-infection with HIV/Hepatitis C

Multiplo Delivers Simultaneous Rapid Diagnosis of HIV and Hepatitis C - XVI International AIDS Conference

Toronto, ON, August 14, 2006 – An estimated 56,000 Canadians are living with HIV infection (The Public Health Agency of Canada) – and 30% of them don’t know it. Another estimated 251,000 Canadians are infected with hepatitis C and, because of the lack of symptoms, 95,000 of them don't know it. (Public Health Agency of Canada)

Up to 33% of those infected with HIV/AIDS are also infected with Hepatitis C (www.hivandhepatitis.com) - prompting some researchers to describe HIV/Hepatitis C co-infection as “the hidden epidemic.”

The issue of co-infection is one of growing concern for delegates at Toronto’s XVI International AIDS Conference this week. MedMira, a leading Canadian manufacturer of reliable, fast, and easy-to-use diagnostics, is launching a tool to make the important diagnosis of HIV/Hepatitis C co-infection much simpler.

Multiplo™ Rapid HIV/HCV Antibody Test (Multiplo HIV/HCV) is the first rapid test to simultaneously identify both HIV and Hepatitis C (HCV) infections.

Co-infected individuals have a more rapid progression of HCV liver disease. In addition, some studies suggest that infection with certain HCV genotypes may accelerate the progression of HIV. HCV may also result in patients discontinuing HIV antiretroviral treatment due to liver toxicity.

“More health agencies and researchers are recognizing the benefits of testing for both HIV and Hepatitis C in the same three-minute procedure. Multiplo HIV/HCV lets you know more and know quickly, so that you can make the right treatment decisions, right away,” says Hermes Chan, President & CEO, MedMira.

Multiplo HIV/HCV is a product that enables healthcare providers and other users to obtain two test results in three minutes or less in comparison to other tests that may take 10 to 40 minutes to obtain just a single result.

Chan continued, “Multiplo HIV/HCV is the first of a series of combination tests that MedMira will launch under the Multiplo line. Multiplo means that with a single specimen, patients and healthcare providers can receive multiple, instant results, without timers, or specialized equipment. One test, more answers.”

MedMira will be showcasing the Multiplo HIV/HCV at the XVI International AIDS Conference in Toronto, from August 13-18th.

About MedMira
MedMira is the leading global manufacturer and marketer of in vitro flow-through rapid diagnostic tests. MedMira’s tests provide reliable, rapid diagnosis in just 3 minutes for the detection of human antibodies in human serum, plasma or whole blood for diseases such as HIV and hepatitis C. The United States FDA, the SFDA in the People’s Republic of China and European Union have approved MedMira’s Reveal® G2, MiraWell® and MiraCare™ rapid HIV tests, respectively. The MedMira Rapid HIV Test has been approved by Health Canada.

MedMira’s Reveal® G2 and MiraWell® rapid HIV tests are currently used in clinical laboratories, hospitals, and clinics where professional counselling and patient treatment are immediately available.

MiraCare™ is sold through MedMira’s distributor network to pharmacies, hospitals and laboratories in the European Union. It is also available over-the-counter (OTC) in pharmacies throughout Hong Kong and Macao Special Administrative Regions, in the People’s Republic of China.

Multiplo HIV/HCV is the first in MedMira’s line of rapid tests for multiple diagnoses of infectious diseases. Multiplo HIV/HCV simultaneously detects HIV and HCV antibodies in a single specimen in less than 3 minutes.

MedMira delivers rapid diagnostic solutions to healthcare communities around the globe. Its corporate offices and manufacturing facilities are located in Halifax, Nova Scotia, Canada with a representative office and joint venture manufacturing facility in Guilin, China.

This news release contains forward-looking statements, which involve risk and uncertainties and reflect the company’s current expectation regarding future events. Actual events could materially differ from those projected herein and depend on a number of factors including, but not limited to, changing market conditions, successful and timely completion of clinical studies, uncertainties related to the regulatory approval process, establishment of corporate alliances and other risks detailed from time to time in the company quarterly filings.

The TSX Venture Exchange has not reviewed and does not accept responsibility for the adequacy or accuracy of this statement.

For more information visit MedMira’s website at www.medmira.com.

For further information
Dr. James Smith, Investor Relations
Tel: 902-450-1588
E-mail: ir@medmira.com

Andrea Young, Corporate Communications
Tel. 902-450-1588
Email: ayoung@medmira.com

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August 16, 2006

Milestone for Promising Hepatitis C Compound

The preliminary results from the Phase 1b study of a compound taken in conjunction with pegylated interferon are expected later this month. This proof of concept milestone indicates progress toward a feasible and functional Hepatitis C treatment. The next step is a Phase 2 trial. We will be anxiously awaiting the results and will report them to you as soon as have them.

ViroPharma and Wyeth Announce Achievement of Proof of Concept Milestone for HCV-796

- Companies Preparing to Initiate Phase 2 Clinical Evaluation -

EXTON, Pa. and COLLEGEVILLE, Pa., Aug. 14 /PRNewswire-FirstCall/ -- ViroPharma Incorporated (Nasdaq: VPHM) and Wyeth (NYSE: WYE) today announced that while the analysis of data from their Phase 1b study of HCV-796, an investigational oral non-nucleoside hepatitis C virus (HCV) polymerase inhibitor, in combination with pegylated interferon, is still ongoing, data analyzed to date indicate that HCV-796 has achieved a "proof of concept" milestone under the companies' agreements. The companies expect that preliminary data from the Phase 1b study will be available for release by the end of August 2006. Based upon the preliminary data reviewed to date, ViroPharma and Wyeth are preparing to initiate Phase 2 combination studies of HCV-796. The companies expect to begin dosing patients in the Phase 2 study in the fourth quarter of 2006.

In connection with meeting the proof of concept milestone, ViroPharma will issue to Wyeth 981,836 shares of ViroPharma's common stock for a purchase price of Ten Million Dollars ($10,000,000), which represents the last of three stock purchases outlined in the companies' agreements. The price per share for the stock was based on a premium to a trailing average price.

"ViroPharma and Wyeth have been partners in hepatitis C antiviral development since 1999; through the years, our goal has been to identify, develop and eventually market drugs to treat hepatitis C patients," said Michel de Rosen, ViroPharma's president and chief executive officer. "HCV-796 is the most promising compound we have developed together to date, and we look forward to announcing the Phase 1b data later this month. The achievement of this milestone and progression toward Phase 2 clinical trials marks an exciting time for us, and a promising opportunity for patients with HCV."

"With HCV-796, we now have for the first time in our collaboration a unique compound with a novel mechanism of action that has achieved proof of concept in combination with pegylated interferon," commented Robert Ruffolo, Ph.D., Wyeth Pharmaceutical's president of research. "We are excited to reach this milestone and to be collaborating with ViroPharma to move this promising compound toward Phase 2 trials."

In December 1999, ViroPharma and Wyeth entered into an alliance to develop and commercialize ViroPharma's lead small molecule antiviral drug candidates for hepatitis C virus (HCV) and to discover, develop and commercialize additional novel inhibitors of HCV. In this agreement, Wyeth agreed to purchase shares of ViroPharma's common stock at the time of completion of certain product development milestones. Under rules promulgated by the Securities and Exchange Commission, ViroPharma is required to publicly file, via Form 8-K, the fact that common stock is being issued in connection with the achievement of the proof of concept milestone.

About HCV-796

HCV-796 is an investigational non-nucleoside polymerase inhibitor compound for the treatment of hepatitis C that is being evaluated in ongoing clinical trials in combination with PEG-Interferon by ViroPharma and Wyeth.

About Hepatitis C

Hepatitis C is a blood-borne virus recognized as a major cause of chronic hepatitis worldwide. The World Health Organization estimates that 170 million persons worldwide are chronically infected with HCV, and three to four million persons are newly infected globally each year. According to the U.S. Centers for Disease Control and Prevention (CDC), about four million people in the U.S., or 1.8 percent of the population, are infected with HCV.

Currently, there is no specific antiviral agent directed against HCV that is commercially available, and no vaccine for prevention of HCV infection. Several interferon (IFN) products are available worldwide, but there are substantial limitations to the use of these products when given as monotherapy or in conjunction with ribavirin in the treatment of chronic HCV infection. In addition to the relatively poor treatment response in patients infected with genotype 1 HCV, the most common strain in the U.S., Western Europe and Japan, the considerable side effects frequently associated with the use of IFN can lead to discontinuation of therapy in approximately 20 percent of patients.

About ViroPharma Incorporated

ViroPharma Incorporated is a biopharmaceutical company dedicated to the development and commercialization of products that address serious diseases treated by physician specialists and in hospital settings. ViroPharma commercializes Vancocin(R), approved for oral administration for treatment of antibiotic-associated pseudomembranous colitis caused by Clostridium difficile and enterocolitis caused by Staphylococcus aureus, including methicillin-resistant strains (for prescribing information, please download the package insert at http://www.viropharma.com/docs/pulvules_pi.pdf). ViroPharma currently focuses its drug development activities in viral diseases including cytomegalovirus (CMV) and hepatitis C (HCV). For more information on ViroPharma, visit the company's website at http://www.viropharma.com.

About Wyeth

Wyeth is one of the world's largest research-driven pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing, and marketing of pharmaceuticals, vaccines, biotechnology products and nonprescription medicines that improve the quality of life for people worldwide. The Company's major divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare and Fort Dodge Animal Health.

Certain statements in this press release are forward-looking statements that involve a number of risks and uncertainties, including those relating to anticipated continued development of HCV-796, clinical development and data release timelines and ability to find an effective small molecule antiviral treatment for HCV disease. Actual results could differ materially from those results expressed in, or implied by, these forward-looking statements. The development and commercialization of pharmaceutical products is subject to risks and uncertainties. There can be no assurance that estimated clinical development and data release timelines will be achieved, Wyeth and ViroPharma's additional HCV studies will yield positive results, or that ViroPharma and Wyeth will be successful in gaining regulatory approval of any of HCV product candidate. These factors, and other factors, including, but not limited to those described in ViroPharma's quarterly reports on Form 10-Q for the quarters ended March 31, 2006 and June 30, 2006 filed with the Securities and Exchange Commission and Wyeth's periodic reports filed with the Securities and Exchange Commission (particularly Item 1A. RISK FACTORS of Wyeth's 2005 annual report on Form 10-K) could cause future results to differ materially from the expectations expressed in this press release. The forward-looking statements contained in this press release may become outdated over time. ViroPharma and Wyeth do not assume any responsibility for updating any forward-looking statements.

SOURCE ViroPharma Incorporated

CONTACT:
ViroPharma Incorporated Contacts:
William Roberts,
Director, Corporate Communications,
+1-610-321-6288,
or Robert Doody,
Manager, Corporate Communications,
+1-610-321-6290;
Wyeth Contacts:
Media:
Gerald Burr,
+1-484-865-5138,
or Douglas Petkus,
+1-973-660-5218,
Investors:
Justin Victoria,
+1-973-660-5340
Web site: http://www.viropharma.com
http://www.viropharma.com/docs/pulvules_pi.pdf /
(VPHM WYE)

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July 17, 2006

New Component Improves HCV Combination Therapy Results

By replacing ribavarin with anti-cholesterol medications, researchers of a recent study improved the effectiveness of combination therapy in preventing the replication of the hepatitis C virus. This is welcome news, particularly to the 45% of chronic hepatitis C patients who do not respond to current combination therapy.

Statins stop hepatitis C virus from replicating
Source: John Wiley & Sons, Inc.
Contact: Amy Molnar
July 6, 2006

A new study shows that statins, which are typically used as anti-cholesterol medications, can inhibit the replication of the hepatitis C virus (HCV). They could replace ribavirin in combination therapy with interferon.

These findings are published in the July 2006 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD).

Currently, 170 million people worldwide are infected with HCV. The standard treatment is a combination therapy of interferon and ribavirin, which is only effective in about 55 percent of patients. The remaining 45 percent face a threat of the disease progressing to cirrhosis and liver cancer. Based on recent reports that one statin, lovastatin, inhibits HCV replication, researchers led by Masanori Ikeda of Okayama University in Japan, tested other statins in search of a more effective anti-HCV therapy.

Using the OR6 cell culture assay system, they evaluated the anti-HCV activities of five statins: atorvastatin, fluvastatin, lovastatin, pravastatin and simvastatin. When the statins were tested alone, all except pravastatin inhibited HCV replication. Fluvastatin had the strongest effect. Atorvastatin and simvastatin had moderate effects while lovastatin had a weak effect. While pravastatin exhibited no anti-HCV activity, it did work as an inhibitor for HMG-CoA reductase, suggesting that the anti-HCV activities of the other stains are not due to the direct inhibition of HMG-CoA.

The researchers determined that the anti-HCV activities of statins were not related to cytotoxicity, meaning they did not kill the host cell. Additional experiments also suggested that, "the statins possess the ability to inhibit the replication of HCV RNA via a specific antiviral mechanism," the authors report.

The researchers tested the theory that certain proteins are required for HCV RNA replication and that statins block the replication by inhibiting those proteins. In support of this theory, they found that the addition of both mevalonate and geranylgeraniol restored HCV RNA replication in the statin-treated cells.

To evaluate statins as potential replacements for ribavirin in combination therapy, the researchers tested the anti-HCV activities of each one when combined with interferon. Each combination, except the one including pravastatin, had even stronger inhibitory effects on HCV RNA replication than when the statin was used alone. Again, fluvastatin plus interferon exhibited the strongest effect. "We clearly demonstrated that co-treatment of interferon and fluvastatin was an overwhelmingly effective treatment," the authors report. This combined therapy was more effective against HCV RNA replication than interferon alone and more effective than the standard combination therapy of interferon and ribavirin.

"Statins are good reagents for combination therapy with interferon in patients with chronic hepatitis C," the authors conclude. "Furthermore, our developed OR6 assay system will be useful for the time-saving screening of new anti-HCV reagents."

The journal Hepatology is published by John Wiley & Sons, Inc.

REFERENCE:
"Different Anti-HCV Profiles of Statins and Their Potential for Combination Therapy with Interferon," Masanori Ikeda, Ken-ichi Abe, Masashi Yamada, Hiromichi Dansako, Kazuhito Naka, Nobuyuki Kato, Hepatology; July 2006; (DOI: 10.1002/hep.21232).

SOURCE: John Wiley & Sons, Inc., Wiley Interscience.

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June 07, 2006

Alert: Fast Track for ACTILON

Hepatitis C patients can add ACTILON to their list of treatments to keep an eye on. After positive preliminary testing, the USFDA granted Fast Track status to this drug designed to sustain immune responses in chronically infected liver patients.

Wellesley, MA - May 17, 2006

Coley Pharmaceutical Group, Inc. (Nasdaq: COLY) today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to ACTILON (CPG 10101) for use in treatment-refractory patients chronically infected with the Hepatitis C virus (HCV).

The Fast Track program of the Food and Drug Administration is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs.

“A Fast Track designation for our ACTILON development program allows Coley to work closely and expeditiously with the FDA to potentially benefit patients who currently have no other treatment alternatives,” said Ferdinand E. Massari, M.D., Senior Vice President, Drug Development and Chief Medical Officer of Coley Pharmaceutical Group.

ACTILON Clinical Development Status
ACTILON is an investigational Toll-like receptor 9 (TLR9) agonist designed to induce both rapid and sustained immune responses that can have durable anti-viral effects.

Positive data from the company’s 12-week Phase Ib clinical study of ACTILON in combination with pegylated interferon and ribavirin among treatment-refractory patients, who had initially responded but then relapsed after treatment with pegylated interferon and ribavirin, were presented in April 2006 at the European Association for the Study of the Liver (EASL) meeting in Vienna, Austria.

A 48-week Phase II clinical study evaluating safety and activity of ACTILON in combination with pegylated interferon and ribavirin is currently enrolling treatment-refractory HCV patients who never responded after a minimum of 12 weeks of pegylated interferon and ribavirin treatment.

About Hepatitis C Treatment-Refractory Patients
Hepatitis C virus, or HCV, is a blood-borne infectious disease of the liver.

Current treatment for HCV infection is a 48-week combination regimen of long-acting interferon and ribavirin. According to the National Institutes of Health, an estimated 42-46 percent of patients treated with pegylated interferon and ribavirin will fail to clear the virus, thus becoming part of the growing “treatment-refractory” population. Treatment-refractory patients number approximately 400,000 in the U.S., with a similar number in Europe. There are no currently available FDA-approved alternative therapies for this population.

About Coley Pharmaceutical Group
Coley Pharmaceutical Group, Inc. is an international biopharmaceutical company, headquartered in Wellesley, Massachusetts, USA, that discovers and develops TLR Therapeutics™, a new class of investigational drug candidates that direct the human immune system to fight cancers, infectious diseases, asthma and allergy. Coley has established a pipeline of four TLR Therapeutic product candidates currently advancing through clinical development either independently or with partners, and additional product candidates in preclinical development. Coley has product development, research and license agreements with Pfizer, sanofi-aventis, Novartis Vaccines & Diagnostics (formerly Chiron), GlaxoSmithKline and the United States government. For further information on Coley Pharmaceutical Group please visit www.coleypharma.com.

Safe Harbor Statement
Certain statements in this news release concerning Coley's business are considered "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, those relating to the future clinical evaluation of a triplet combination therapy including ACTILON for the treatment of HCV, and the design and enrollment of Coley’s Phase II study of ACTILON in combination with pegylated interferon and ribavirin. Any or all of the forward-looking statements in this press release may turn out to be wrong. They can be affected by inaccurate assumptions Coley might make or by known or unknown risks and uncertainties, including, but not limited to: the early stage of product development; uncertainties as to the future success of ongoing and planned clinical trials; and the unproven safety and efficacy of products under development and other risks identified in Coley’s filings with the Securities and Exchange Commission including, but not limited to, Coley’s Annual Report on Form 10-K for the fiscal year ended December 31, 2005. Consequently, no forward-looking statement can be guaranteed, and actual results may vary materially. Coley undertakes no obligation to publicly update forward-looking statements, whether because of new information, future events or otherwise, except as required by applicable law.

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June 06, 2006

3 New Combination Therapies

New combinations of therapies are making significant progress in improving hepatitis symptoms. Learn more about these progressive treatments.

LOS ANGELES (May 21, 2006) According to recent estimates, hepatitis has become a worldwide health problem, affecting millions of people in the U.S. and abroad. Researchers are experimenting with combinations of anti-inflammatory medicines like interferons to improve hepatitis symptoms. In research presented today at Digestive Disease Week® 2006 (DDW), new combinations of therapies are making significant progress to improve symptoms of the disease. DDW is the largest international gathering of physicians and researchers in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.

Hepatitis is caused by a virus that attacks the liver, triggering painful inflammation and often leading to more serious conditions like liver failure and even death. Several different forms of hepatitis exist, including hepatitis A, B and C. Hepatitis A is generally food-borne, while hepatitis B and C are spread primarily through parenteral or sexual routes. The disease is often caused by a virus, but can also result from alcohol, toxins or drugs.

"Despite the significant number of people suffering from hepatitis, treatment options have been lagging in comparison to other major diseases," said John Vierling, M.D., FACP, president, the American Association for the Study of Liver Diseases (AASLD); professor of Medicine and Surgery at the Baylor College of Medicine in Houston, Texas; and director of Baylor Liver Health and Chief of Hepatology. "We hope that continued research like these studies will lead to more significant breakthroughs and relief for these patients."

Valopicitabine (NM283), Alone or with Peg-Interferon, Compared to Peg Interferon/Ribavirin (pegIFN/RBV) Retreatment in Hepatitis C Patients with Prior Non-Response to PegIFN/RBV: Week 24 Results [Abstract 4]

More than half of currently treated hepatitis patients are infected with strains of hepatitis C that do not respond to current interferon therapies and have no other effective treatment options. Combination treatment using a new antiviral therapy is showing promise in suppressing the virus, according to a phase II US multi-center study. The therapy, valopicitabine, has shown anti-HCV activity alone and in combination with pegIFN (pegylated interferon) in early trials, without viral breakthrough for study periods up to six months.

The current study compared the outcomes of five different treatments in patients who have not experienced remission with standard therapies: valopicitabine alone (800 mg/d), one of three combination arms with the drug at 400 mg/d, 800 mg/d or dose-ramping 400 to 800 mg/d plus pegIFN, or pegIFN with ribavirin as a control group.

For the 162 patients who have completed the trial period at 24 weeks, results show that the two higher-dose combination arms had much better response rates than the control group, experiencing on average a 2.5 to 3.0 log decrease in hepatitis RNA reductions by week 24, a significantly better response than the comparator. No viral breakthrough has been seen to date. However, vomiting and dehydration requiring hospitalization occurred in three patients taking the highest dose (800 mg), forcing the research team to halt the use of that dose and continue using only the lower doses of 200 to 400 mg of the drug.

"For patients whose disease has not responded to current therapies, this new combination treatment may produce excellent results, at the maximally acceptable dosage," according to Paul Pockros, M.D., of Scripps Clinic in California, and lead study author. "Continued treatment will determine if these encouraging early responses will result in a sustained response, hopefully improving patient quality of life and long-term survival."

Comparison of Daily Consensus Interferon versus Peginterferon alfa 2a Extended Therapy of 72 Weeks for Peginterferon / Ribavirin Relapse Patients with Chronic Hepatitis C [Abstract S1060]

In chronic diseases like hepatitis, symptoms have a tendency to fluctuate in severity. As a result, researchers are finding that the diseases may react more successfully to a longer duration of therapy. In this study, researchers at the University of Tuebingen in Germany compared two combination therapies for an extended treatment period of 72 weeks, compared to the current standard of 48 weeks, in patients with chronic hepatitis C.

Previous studies have shown that with 48 weeks of therapy, relapse rates are near 20 to 30 percent, but with an extended duration of 72 weeks, rates may be reduced. The research team compared the efficacy of daily doses of CIFN (consensus interferon) plus ribavirin (RBV) versus pegIFN (pegylated interferon alfa 2a) plus RBV for 72 weeks in patients with a prior relapse to 48 weeks of treatment. A total of 81 patients were treated with either CIFN or with pegIFN a2a for 72 weeks, both in combination with RBV.

After the initial 12 weeks, a primary response to therapy, noted as a reduction in hepatitis RNA, was observed in 83 percent of patients in the CIFN group and 78 percent of the pegIFN group. At the end of treatment at week 72, the vast majority (89 percent) of both the CIFN group and pegIFN group (76 percent) were in remission. After finishing treatment, two-thirds of the CIFN group (69 percent) experienced sustained response, but less than half of the pegIFN group (44 percent) experienced these results, indicating a significantly higher relapse rate in this group.

"While many patients did relapse after discontinuing treatment, the overall sustained response rates are nevertheless promising, showing a sustained response in up to 70 percent of patients," said Stephan Kaiser, M.D., of the University of Tuebingen, and lead study author. "We believe that extended treatment with CIFN combined with RBV may be a better option than current standards for this difficult-to-treat patient group."

The overall tolerability of the CIFN regimen was comparable to PEG IFN. Three patients experienced thrombocytopenias (reduced blood platelets), but there were no severe neutropenias (low white blood cell count) or thrombocytopenias. CIFN patients experienced a higher rate of injection site reactions and a slightly higher drop-out rate of 18 percent, compared to only 12 percent of the pegIFN group.

28 Days of the Hepatitis C Protease Inhibitor VX-950, In Combination with Peg-Interferon-Alfa-2a and Ribavirin, is Well-Tolerated and Demonstrates Robust Antiviral Effects [Abstract 686f]

Scientists are reviewing new compounds in combination with current standard hepatitis therapies to produce better patient outcomes. A new oral peptidomimetic protease inhibitor, VX-950, has previously shown substantial anti-viral effects in combination with the frequently used hepatitis therapy pegylated interferon (pegIFN). In this study, researchers evaluated the safety and antiviral response of VX-950 in combination with pegIFN and ribavirin (RBV).

The study included 12 hepatitis C patients who received 750 mg of VX-950 every eight hours, 180 ìg of pegIFN weekly, and either 1000 or 1200 mg of RBV daily. After 28 days, patients began standard therapy with pegIFN/RBV.

All patients responded to the study drug regimen and showed continual declines in hepatitis RNA throughout the treatment period. Two patients had levels of HCV RNA in their blood below the limits of detection of a highly sensitive assay after just eight days. All patients had undetectable HCV RNA by the end of 28 days. No patients experienced viral breakthrough at any time.

"These data confirm the rapid and dramatic antiviral effects of VX-950. All subjects achieving undetectable HCV RNA within 28 days of treatment is an unprecedented result with an investigational agent," said Eric Lawitz, M.D., of Alamo Medical Research, Texas, and lead author of the study. "We look forward to future studies which will evaluate the ability of VX-950 to produce sustained viral responses with as little as 12 weeks of therapy."

VX-950 + pegIFN + RBV was well tolerated, with no serious adverse events and no treatment discontinuations. A detailed analysis of adverse events will be presented.

###

Digestive Disease Week® (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW takes place May 20-25, 2006 in Los Angeles, California. The meeting showcases more than 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology.

Reprinted with permission of Digestive Disease Week® 2006.

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April 14, 2006

Replication Discovery Provides New Treatment Approach

The recent discovery that the Hepatitis C virus needs a small part of RNA found only in the liver to replicate itself has sparked new treatment approaches. If researchers can determine whether lowering the amount of this RNA decreases viral load without adversely affecting the liver we may see a promising breakthrough.

April 5, 2006
Stanford Office of Communication and Public Affairs

STANFORD, Calif. — Last year Peter Sarnow, PhD, professor of microbiology and immunology at the Stanford University School of Medicine, identified a previously unknown mechanism that the hepatitis C virus uses to replicate, yielding a promising new approach to combating the disease-causing virus. On April 5 at the Experimental Biology meeting in San Francisco, Sarnow will discuss recent developments in this work—including his partnership with two pharmaceutical companies that seeks to use the new understanding of the virus to develop treatments.

According to the World Health Organization, hepatitis C virus infects 170 million people worldwide. About 70 percent of those infected develop liver disease, including cirrhosis and liver cancer. In the United States, it is the most common blood-borne viral infection, killing more than 10,000 people each year. Currently available treatments are expensive and do not work in about half of the cases.

“Normally with an RNA virus like hepatitis C, resistance to antivirals very quickly emerges, so the drug is not effective any more,” said Sarnow, who has been studying the virus for years, sorting out how the viral RNA amplifies in cultured liver cells.

In the normal sequence of events, genetic information is stored in DNA and then is copied into RNA, which serves as a template to create proteins. With RNA viruses such as hepatitis C, the genetic information is stored in RNA instead of DNA.

RNA is genetically more unstable than DNA, resulting in the accumulation of many mutations. These mutations allow the virus to outwit the immune system and develop resistance to antiviral medication.

Sarnow’s group has shown that a small fragment of RNA found in the liver, known as a microRNA, is necessary for hepatitis C to grow and reproduce. Their work, published in September 2005 in the journal Science, is the first to link the presence of a specific microRNA with a major infectious disease.

When the researchers inactivated the microRNA, called miR-122, the amount of hepatitis C virus RNA was reduced by approximately 80 percent. “The cool thing is that here, an antiviral is encoded by a host function and not by the virus — so it cannot change,” said Sarnow. In other words, because the virus needs miR-122 to replicate, there is no way the virus could develop resistance to a strategy that inactivates miR-122.

A couple of years ago, Sarnow learned that other scientists had discovered miR-122, found only in the liver. He knew that there could be up to 65,000 copies of miR-122 per cell in the liver. “And we know that the virus can persist in the liver for as long as 30 years, so we made the hypothesis that the virus might interact with miR-122 in some way,” he said. “It turns out that yes, the virus grabs it for its own good.”

“This is a completely different way for microRNA to interact with its target from what is known and it brings up the idea that other microRNAs might work like that,” said Catherine Jopling, PhD, a postdoctoral researcher in Sarnow’s laboratory who spearheaded the work. “But nobody’s been looking for that.”

The researchers think that their findings may have therapeutic potential for a new antiviral target that does not attack the virus directly.

“If you can lower the amount of the microRNA in the liver without affecting liver function maybe this will help lower the viral load,” said Sarnow. Stanford has entered into a licensing agreement with Alnylam Pharmaceuticals and Isis Pharmaceuticals to explore the possibility of using miR-122 as a novel therapeutic against hepatitis C.

The big question is what does this microRNA normally does in the liver. It is possible that lowering microRNA levels in the liver might produce an undesirable outcome, such as cancer, said Sarnow. However, recent promising reports from researchers at Rockefeller University, Alnylam and Isis have demonstrated that miR-122 can be inactivated in mouse liver for some time without impairing liver function.

The Experimental Biology meeting is an annual gathering of groups covering a range of scientific disciplines, including anatomy, biochemistry, molecular biology, pharmacology and pathology. This year 12,000 scientists are expected to attend the event at the Moscone Center in San Francisco.

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March 30, 2006

Ability to Culture Hepatitis C Virus Leads to Research Advancements

By overcoming the difficulties of culturing live HCV, scientists are now capable of studying the virus more closely. We anticipate this progress will open the door to hepatitis C treatment and prevention.

Researchers show laboratory hepatitis C strain is also infectious in animal models
27 March 2006
Rockefeller University Newswire

An important step in developing a treatment for viral diseases is for scientists to culture live viruses from infected patients, but the hepatitis C virus (HCV), a major cause of chronic and sometimes fatal liver disease, has proven to be particularly wily. For many years scientists have struggled with an inability to efficiently culture HCV in the laboratory. Now, researchers at Rockefeller University have overcome several obstacles and successfully shown that a strain of HCV they created in the laboratory, which can efficiently be cultured in vitro, is also infectious in animals. The findings, reported in the March 7 issue of the Proceedings of the National Academy of Sciences, will enable scientists to study the life cycle of HCV at the molecular level and develop better treatments for this disease.

The researchers, led by Brett Lindenbach at Rockefeller and Philip Meuleman at Ghent University in Belgium, used a cell-culture version of HCV, developed by Lindenbach and colleagues at Rockefeller, called HCVcc. HCVcc, which was the first infectious cell-culture version of hepatitis C, was used to infect two chimpanzees as well as mice bearing human liver grafts. The researchers found that in both the chimpanzees and the mice, hepatitis C infection lasted for as long as 15 weeks. Also, the infections raised in the mice could be passed to other mice. Samples of the test tube-cultured strain could be recovered from infected animals and was easily recultured in vitro, unlike most other strains of HCV isolated from infected animals or people.

“The ability to study a genetically defined virus in the test tube and in living animals allows us to completely dissect the HCV life cycle,” says senior author Charles Rice, Maurice R. and Corinne P. Greenberg Professor and head of the Laboratory of Virology and Infectious Disease at Rockefeller.

The chimpanzees, which are housed at the Southwest National Primate Research Center in San Antonio, Texas, were previously used for studies of HIV and other strains of hepatitis, and were not infected with HCV before being inoculated with HCVcc. The mouse experiments, which took place at Ghent University, involved a strain of mice called uPA-SCID, which lack an immune system and mimic the liver failure that can accompany chronic hepatitis C infection in people.

In addition, the researchers found that the virus recovered from the experimentally infected animals had a higher infectivity than the original HCVcc. They also found that virus particles with a lower buoyant density — a measure of how well they float — had increased infectivity, suggesting that differences in the physical properties of the viruses grown in vitro and in vivo are important for biological activity.

These results show that it should be possible to culture HCV from clinical samples and provide a useful positive control to help isolate additional strains that grow in cell culture, Lindenbach and Rice say.

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February 20, 2006

A Breakthrough Discovery for Hepatitis C

Biologists at Florida State University have recently produced a study illuminating the replication and mutation of the Hepatitis C virus. This kind of progress represents a giant leap forward in tracking this persistent virus, which likely means more accurate and efficient therapy will be coming soon.

LANDMARK FSU STUDY OF HEPATITIS C VIRUS SOLVES MYSTERY THAT HAS STYMIED QUEST FOR CURE

By Libby Fairhurst
February 7, 2006

TALLAHASSEE, Fla. --The hepatitis C virus (HCV) infects more than 170 million people worldwide and leads to both acute and chronic liver diseases. Since its discovery several decades ago, the insidious human pathogen has stymied the quest for anti-viral therapies by refusing to reproduce in test tubes for more than a few hours or days, denying scientists an efficient virus production and infection system for experimental research.

Now, in a landmark study by Florida State University biologists that could bolster the development of anti-viral therapies for HCV -- as well as for related RNA viruses such as West Nile and influenza -- Assistant Professor Hengli Tang and doctoral student/co-author Heather B. Nelson have discovered the molecular mechanism that inhibits HCV replication in vitro after its host cells become crowded and stopped dividing.

What's more, their groundbreaking discovery came about as a result of the new test they developed that can quickly and easily monitor HCV replication in the laboratory. Finally, after Tang and Nelson uncovered the reason for suppression of the virus in cell culture -- in a nutshell: not enough nucleotide molecules, the building blocks of HCV -- they then adapted an existing cell technology to remedy the problem right in the test tube.

The Tang-Nelson study and a description of the innovative technologies they devised to enable and track it will appear in the Feb. 8 edition of the Journal of Virology."Our findings could prove critical to research on HCV's complex virus-host cell interactions and lead to better, targeted treatments," Tang said. "Currently, any nucleotide starvation therapies, used primarily to treat cancer, can inhibit replication by depriving viral agents of their molecular building blocks. However, those therapies may impact healthy cells, as well, causing undesired side effects."

In the human liver, the parasitic HCV makes copies of its genetic material by hijacking nucleotides -- the little molecules produced by its dividing host cells. It is only in the liver that pools of nucleotides remain available to HCV in sufficient supply after the host cells reached confluence (stop dividing). Not so in test tubes, say the FSU researchers.

To address the shortage of HCV building blocks in vitro, their unique adaptation of an existing cell technology enabled the introduction of nucleoside molecules to a culture of liver cancer cells. The nucleosides then converted to the essential nucleotide molecules that Tang calls the missing link. In turn, the nucleotides generated in vitro replication of infectious HCV particles that continued even after host cell confluence -- as it does in the liver.

That's not all. "Our new cell line also allows us to rapidly identify and isolate drug-resistant HCV mutants in vitro and to screen for anti-viral drug candidates," Tang said. "This will help researchers better study the mechanism of drug resistance, a big problem with this virus and others such as HIV (human immunodeficiency virus) that mutate quickly."

Underpinning everything, Tang says, is their novel, easy-to-use assay. It can track mutant strains of HCV in a week or less while other assays take weeks or months.

"Our assay, for which FSU has filed a provisional patent application, employs a new reporter cell line, which means the cells give out a detectable signal when certain events happen inside them," said Tang. "In this case, they emit a green fluorescence whenever HCV is replicating. The fluorescence is tracked in the cell culture through a technique known as flow cytometry, which employs a machine equipped with a laser and lights that follows the green to find the virus."

Between earning his PhD at the University of California-San Diego in 1998 and joining FSU's biological science faculty in 2004, Tang served as a lead researcher in an industry setting, seeking targeted anti-viral therapies primarily for HIV.

"I find it particularly rewarding to play a part in research that may actually help somebody soon," he said.

The Tang-Nelson study at FSU -- "Effect of Cell Growth on Hepatitis C Virus (HCV) Replication and a Mechanism of Cell Confluence-Based Inhibition of HCV RNA and Protein Expression" -- was supported in part by a grant from the American Heart Association.

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February 02, 2006

SCH 503034 Jumps on the Fast Track

Schering-Plough's oral HCV protease inhibitor, SCH 503034, is in phase II trials, and may make for a better combination with Peg-intron. Check-in with us regularly, as we will be keeping close tabs on this development.

Schering Hepatitis Drug Gets Fast Track Status

Pharmaceutical Business Review Online
February 1, 2006

By Staff Writer

The FDA has agreed to review Schering-Plough's investigational oral hepatitis C drug on a fast track basis, potentially allowing the treatment to reach the market quicker.

The drug, named SCH 503034, is an orally active inhibitor of the hepatitis C virus (HCV) serine protease that inhibits HCV replication. This mechanism is distinct from those of current therapies, thus SCH 503034 represents a novel class of HCV inhibitor. The treatment is currently in phase II clinical development.

Fast track designation allows FDA to expedite review of drugs and biologics for serious or life-threatening conditions and which demonstrate the potential to address unmet medical needs. An important feature of fast track designation is that it emphasizes the critical nature of close, early communication between the FDA and the sponsor company to improve the efficiency of product development.

SCH 503034 has demonstrated potent antiviral activity and was well- tolerated, both as monotherapy and in combination with another of the company's products Peg-intron (peginterferon alfa-2b). In phase I clinical studies patients chronically infected with HCV genotype 1 who had not responded to previous therapy seemed to benefit from SCH 503034.

Based on the results of the phase I clinical program and extensive preclinical safety and pharmacology studies, Schering-Plough is conducting a large, randomized phase II dose-finding study involving 300 patients worldwide. This study is further evaluating the safety and efficacy of SCH 503034 in combination with Peg-intron.

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January 17, 2006

MedMira Rapid Test

The start of the New Year was accompanied by the European Patent Office granting a patent for a rapid HCV test. Now that the technology is here, let's hope the test proves accurate, with high levels of selectivity and specificity.

MedMira Granted Hepatitis C Patent in Europe

Patent Further Protects MedMira's Diagnostic Technology

HALIFAX, Jan. 3 /PRNewswire-FirstCall/ - MedMira Inc., ("MedMira") (TSX Venture: MIR, NASDAQ: MMIRF) the global market leader in premium rapid diagnostic solutions, announced today that it has been granted a patent for the HCV Mosaic Antigen by the European Patent Office. This is the company's first major patent on its rapid diagnostic technology in Europe, and paves the way for the world's first combination HIV and Hepatitis C instant rapid test.

Hepatitis C (HCV) impacts over 170 million people worldwide according to the World Health Organization, which also indicates over 40% of individuals with HIV are co-infected with HCV. A combination rapid HIV/HCV test can play a critical role in patient outcomes.

Patent No. EP 1328 811 B1 will ensure that MedMira's rapid HCV diagnostic technology is protected as it is brought to market in Europe. The patented technology is a key component in MedMira's rapid HCV tests and HIV/HCV combination tests slated for market entry in 2007.

"We are very pleased to receive this patent for our groundbreaking technology," said Hermes Chan, president and COO of MedMira, and principal inventor of the HCV Mosaic Antigen. "Considerable R&D efforts were dedicated to developing this technology in the past years. Protecting this valuable diagnostic solution through the patent process was an important step in bringing the complete line of rapid HCV diagnostic products to the European market."

The HCV Mosaic Antigen is a highly immunoreactive mosaic antigen composition containing a plurality of different antigenic peptides encoded from the core region of the HCV genome. The granted patent also describes a test kit utilizing the antigen, and a method for its use for the purpose of detecting antibodies to HCV in a test sample.

About MedMira

MedMira is the leading global manufacturer and marketer of in vitro flow-through rapid diagnostic tests. MedMira's tests provide reliable, rapid diagnosis in just 3 minutes for the detection of human antibodies in human serum, plasma or whole blood for diseases such as HIV and hepatitis C. The United States FDA and the SFDA in the People's Republic of China have approved MedMira's Reveal(TM) G2 and MiraWell(R) rapid HIV tests, respectively.

MedMira's Reveal(R) G2 and MiraWell(R) rapid HIV tests are currently used in clinical laboratories, hospitals, and clinics where professional counselling and patient treatment are immediately available.

The MiraCare(TM) Rapid HIV Antibody Test, MedMira's over-the-counter (OTC) product, is available in pharmacies throughout Hong Kong and Macao Special Administrative Regions, in the People's Republic of China.

This news release contains forward-looking statements, which involve risk and uncertainties and reflect the company's current expectation regarding future events. Actual events could materially differ from those projected herein and depend on a number of factors including, but not limited to, changing market conditions, successful and timely completion of clinical studies, uncertainties related to the regulatory approval process, establishment of corporate alliances and other risks detailed from time to time in the company quarterly filings.

The TSX Venture Exchange has not reviewed and does not accept responsibility for the adequacy or accuracy of this statement.

For more information visit MedMira's website at http://www.medmira.com.

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January 09, 2006

GlobeImmune Recruiting for Clinical Trial

While GlobeImmune's therapeutic vaccine for Hepatitis C is only in Phase Ib of clinical trials, their focus on immunity to the Hepatitis C virus is fascinating. GI-5005 is based on tarmogens being potent activators of antigen-specific immune responses against disease.

Safety and Efficacy of the Therapeutic Vaccine GI-5005 Versus Placebo for the Treatment of Chronic Hepatitis C Infection

This study is currently recruiting patients.
Verified by GlobeImmune July 2005
Sponsored by: GlobeImmune
Information provided by: GlobeImmune
ClinicalTrials.gov Identifier: NCT00124215

Purpose:
The GI-5005 therapeutic vaccine or placebo will be injected under the skin of hepatitis C virus (HCV) subjects. Patients will be monitored for safety, immune responses and any therapeutic benefits related to the injections.

Condition	Intervention	Phase
Hepatitis C	Vaccine: GI-5005	Phase I

MedlinePlus related topics: Hepatitis C

Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Single Group Assignment, Safety/Efficacy Study

Official Title: A Phase 1 Double-Blind, Placebo Controlled, Dose-Escalation, Multi-Center Therapeutic Trial of the Safety, Immunogenicity, and Efficacy of GI-5005; an Inactivated Recombinant Saccharomyces Cerevisiae Expressing a Hepatitis C Virus NS3-Core Fusion Protein, in Patients With Chronic Hepatitis C Infection

Further study details as provided by GlobeImmune: GI-5005 targets two HCV antigens which are highly conserved, abundant and essential for virus replication. GI-5005 has demonstrated robust activity in preclinical models of HCV. Because the body’s response to Tarmogens resembles successful natural immunity to the hepatitis C virus, the Company believes that the GI-5005 Tarmogen may represent a successful approach to treating this difficult disease. The Company initiated a Phase 1b trial at five US centers for GI-5005 in July 2005.

Expected Total Enrollment: 48

Study start: June 2005

Eligibility:
Ages Eligible for Study: 18 Years and above
Genders Eligible for Study: Both Criteria

Inclusion Criteria:
• Patients with chronic hepatitis C virus infection including treatment naive subjects as well as subjects who are partial responders and relapsers to prior interferon therapy
• >18 years of age
• Negative skin test for hypersensitivity to saccharomyces cerevisiae.

Exclusion Criteria:
• Non-responders to previous interferon treatments
• Cirrhosis
• HCV treatment within 3 months
• Hepatitis B infection
• HIV infection

Location and Contact Information:
Please refer to this study by ClinicalTrials.gov identifier NCT00124215
John Ferraro 720-859-4134

California
Huntington Medical Research Institutes, Pasadena, California, 91105, United States; Recruiting
Ruth Co 626-397-5825
Myron Tong, M.D., Principal Investigator

Colorado
University of Colorado Health Sciences Center, Denver, Colorado, 80262, United States; Recruiting
Jennifer DeSanto 303-315-1128
Gregory Everson, M.D., Principal Investigator

Florida
University of Miami, Miami, Florida, 33136, United States; Recruiting
Angelique Brown 305-243-2184
Eugene Schiff, M.D., Principal Investigator

Illinois
University of Chicago, Chicago, Illinois, 60637, United States; Recruiting
Katie Wherity 773-702-4477
Helen Te, M.D., Principal Investigator
Donald Jensen, M.D., Sub-Investigator

New York
Weill Medical College of Cornell University, New York City, New York, 10021, United States; Recruiting
Mary Ahern 212-746-2115
Ira Jacobson, M.D., Principal Investigator

More Information:
Sponsor's website: http://www.globeimmune.com
Study ID Numbers: GI-5005-01
Last Updated: December 8, 2005
Record first received: July 25, 2005
ClinicalTrials.gov Identifier: NCT00124215
Health Authority: United States: Food and Drug Administration

Posted by Editors at 02:23 PM --- Printer-friendly version

December 08, 2005

VX-950 To Get Fast Tracked

As you may recall we've been saying VX-950 is the revolutionary new therapy to watch for HCV. Now it looks like the FDA agrees this treatment is quite promising and deserving of faster approval than a lesser worthy approach. Another reason they are doing this is they know current therapy options are less than ideal.

UPDATE 1-Vertex hepatitis C drug will get fast track review
Thu Dec 8, 2005 11:07 AM ET

BOSTON, Dec. 8 (Reuters) - Vertex Pharmaceuticals Inc. (VRTX.O: Quote, Profile, Research) said on Thursday that U.S. regulators will review its experimental hepatitis C drug on an accelerated basis.

The Cambridge, Massachusetts-based company said the U.S. Food and Drug Administration granted "fast track" status to the drug, VX-950, a designation given to drugs aimed at treating serious or life-threatening conditions.

The drug is currently in early clinical trials and the company won't be ready to submit a marketing application until 2008, according to Joshua Boger, its chief executive officer.

Fast track status will, however, speed the drug's journey to the market as Vertex will have more frequent contact with the FDA, and it will be able to submit data from its clinical trials as it comes in, rather than waiting until the entire package is complete.

Hepatitis C is a liver disease caused by a virus in the blood. It affects about 3.4 million people in the United States.

Vertex's drug is an oral treatment that goes into the blood stream and blocks the HCV protease, a protein the hepatitis C virus makes in the liver cells. Blocking the protein prevents the virus from reproducing.

The company hopes that the drug will dramatically shorten the time it takes to eliminate the virus from the blood stream. Current treatments typically take a year to reduce the virus to undetectable levels and only work in about 50 percent of patients.

The current standard of care is a combination of pegylated interferon and ribavirin. Vertex plans to test its drug in combination with pegylated interferon next year.

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December 02, 2005

Indenix is Nearing Phase III for Valopicitabine

It is always good to see progress with alternatives to current medical therapy for HCV. Even though companies that are working on solutions to be used with interferon are not really offering anything groundbreaking or revolutionary, it does continue the evolution of treatment.

The fact that Valopicitabine is nearing Phase III studies is certainly notable. No other seems to be that far along.

Idenix Provides Update on Clinical Development Program for Valopicitabine (NM283) for the Treatment of Hepatitis C

CAMBRIDGE, Mass., Dec. 2 /PRNewswire-FirstCall/ -- Idenix Pharmaceuticals, Inc., (Nasdaq: IDIX), announced today that the company met with the United States Food and Drug Administration (FDA) on November 30, 2005 to discuss the clinical development program for valopicitabine (NM283) for the treatment of hepatitis C.

Based upon this meeting, the company anticipates finalizing the study design for a phase III clinical trial in treatment-refractory patients by the end of the first quarter of 2006 and starting to enroll patients thereafter. At the meeting, the FDA requested additional information from the two ongoing phase IIb clinical trials evaluating valopicitabine. In response, Idenix plans to provide the FDA with comprehensive 24-week data from the ongoing phase IIb clinical trial in treatment-refractory patients.

Idenix also expects to provide initial data from the ongoing phase IIb trial evaluating valopicitabine in treatment-naive patients, which includes a patient cohort receiving valopicitabine 800 mg plus pegylated interferon beginning on day 1 of treatment. This is the treatment regimen that the company currently expects may be evaluated in phase III clinical trials. The company anticipates that it will provide in January 2006 these additional data that have been requested and thereafter meet with the FDA to review such additional data.

At that meeting, the company anticipates further discussing with the FDA the proposed phase III clinical trial protocol. "We are pleased with the interaction we have had with the FDA to date regarding valopicitabine development," said Jean-Pierre Sommadossi, chief executive officer of Idenix. "We are optimistic that we will continue to advance the valopicitabine clinical program, particularly in view of the serious unmet need in the treatment-refractory patient population in hepatitis C," he said.

About Valopicitabine
Valopicitabine, which is administered orally once a day, is intended to block HCV replication by specifically inhibiting the HCV RNA polymerase, the enzyme that makes new copies of HCV viral chromosome inside infected cells. Initial phase I clinical trials sponsored by Idenix showed that valopicitabine is active in patients infected with the genotype 1 strain of HCV, the strain that infects the majority of patients in North America, Europe, and Japan. The ongoing clinical trials are designed to evaluate the combination of valopicitabine and pegylated interferon in hepatitis C genotype 1 patients who previously failed to respond to antiviral treatment, as well as in genotype 1 patients who have not been treated previously. Preliminary results from phase II clinical trials to date have demonstrated that the antiviral effect of valopicitabine is enhanced when this agent is used in combination with pegylated interferon.

About Hepatitis C
Hepatitis C is an infectious liver disease caused by the hepatitis C virus. The World Health Organization estimates that 170 million individuals worldwide carry chronic HCV infection, with 3 to 4 million new infections occurring globally each year. It is the most common chronic blood-borne infection in the United States, with 2.7 million people chronically infected. Chronic HCV infection causes inflammation of the liver, which may cause progressive liver damage that can lead to liver scarring, liver cancer, liver failure, and death. Patients infected with HCV genotype 1 are difficult to treat, with half or fewer such patients achieving sustained responses to current standard treatment regimens involving a combination of pegylated interferon plus ribavirin. These "non-responders" or treatment-refractory patients comprise a growing patient population, who have no proven alternative treatments available and who are at risk for progressive HCV-associated liver disease. As the prevalence of severe liver disease attributable to chronic hepatitis C rises, deaths due to complications from hepatitis C infection, currently 8,000 to 10,000 per year in the United States, are expected to increase dramatically over the next 15 to 20 years.

About Idenix
Idenix Pharmaceuticals, Inc. is a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral and other infectious diseases. Idenix's current focus is on the treatment of infections caused by hepatitis B virus, hepatitis C virus and human immunodeficiency virus (HIV). Idenix's headquarters are located in Cambridge, Massachusetts and it has drug discovery and development operations in Montpellier, France and drug discovery operations in Cagliari, Italy. For further information about Idenix, please refer to http://www.idenix.com.

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November 22, 2005

Vertex Progresses with VX-950

Vertex is the racehorse to watch right now. They are progressing quicky on their preliminary good results.

While it's not yet time to line up for their treatment, we believe theirs will be first to market of the new approaches (although there can still be serious unforseen setbacks).

Vertex Announces Filing of IND in Support of VX-950 Phase II Development in the U.S.

SAN FRANCISCO, Nov. 11 /PRNewswire-FirstCall/ -- Clinical data being presented this week while attending the 56th American Association for the Study of Liver Diseases (AASLD) Annual Meeting confirm that VX-950, an investigational oral hepatitis C protease inhibitor developed by Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX), was well-tolerated and possessed potent antiviral activity in a 14-day study in patients with hepatitis C virus (HCV) infection.

The rapid decline in plasma HCV-RNA levels observed in HCV patients taking VX-950, together with a viral kinetic analysis that projects the potential duration of treatment required to achieve sustained virologic response (SVR), support the evaluation of VX-950 in a novel, three-month combination treatment paradigm.

Vertex also announced today that it has filed an investigational new drug application (IND) with the U.S. Food and Drug Administration (FDA) to support Phase II clinical development of VX-950. "The clinical data demonstrate a swift and dramatic decline in viral levels with VX-950, and provide insight into VX-950's potential to transform future HCV treatment," said Joshua Boger, Ph.D., Chairman, President and Chief Executive Officer of Vertex. "Our clinical development effort is gaining momentum, as indicated by our recent IND submission with the FDA to support the planned initiation before year-end of the first clinical study in what we expect will be a broad Phase II program."

Phase Ib Study Clinical Results: Major Findings Five presentations taking place at the meeting provide a comprehensive analysis of the Phase Ib study of VX-950 given as monotherapy. Results being presented at the conference are from a dose-ranging Phase Ib study of VX-950 dosed in an oral suspension for 14 days in patients with chronic hepatitis C. Dr. Henk Reesink, Principal Investigator for the study, will present the major findings in an oral presentation at the Presidential Plenary Session and at a press conference on Monday, November 14.

In the Phase Ib study, VX-950 in all dose groups exhibited substantial antiviral effects, with 26 of 28 patients receiving any dose of VX-950 achieving more than a 3-log reduction in plasma HCV-RNA within two days. After 14 days, patients in the best dose group (750 mg every 8 hours) achieved a mean reduction in HCV-RNA of 4.4 log10, a 25,000- fold reduction in viral levels. In the trial, VX-950 was well-tolerated. Overall in the Phase Ib study, adverse events observed in patients receiving VX-950 that were considered possibly related to the drug were mild, and generally similar in frequency to events in the placebo group.

The most common adverse events reported in both placebo and VX-950 patients were headache, frequent urination, and gastrointestinal symptoms.(1) In a separate analysis of the Phase Ib trial results to be presented in detail in a poster presentation on Tuesday, November 15, Vertex researchers analyzed the relationship between blood concentrations of VX-950 and antiviral effect over 14 days.

A dose-response was established with higher ranges of VX-950 blood concentrations being associated with a better outcome relative to the responses established at lower blood concentrations of VX-950. The researchers found that the steep decline in plasma HCV-RNA seen in patients during the first two days was correlated closely with total blood concentrations during the first dosing interval, as measured by area under the curve (AUC). In addition, the achievement of a greater than 3.5 log10 reduction in plasma HCV-RNA at day 7 or greater than 4.5 log10 reduction at the end of the full 14 days of treatment was closely correlated with blood concentrations at "trough" (minimum concentration in blood immediately prior to receiving the next dose). Further, these researchers analyzed the viral kinetics to estimate the treatment duration required to achieve viral eradication. In this analysis, researchers projected the continued slope of viral decline that could be expected with dosing beyond 14 days in the patients who achieved HCV-RNA levels below the limit of quantitation at the end of dosing in the Phase Ib study.

The results of this simulation suggest that, with continued steep viral decline on treatment, it may be possible with approximately 12 weeks of treatment to reduce levels of HCV-RNA in patients to less than 10 viral copies (total body viral load). A total body viral load in this range is considered to be what may be required for potential host eradication of infection and achievement of SVR. Vertex is taking the encouraging results of this viral kinetic analysis into account in the design of planned Phase II clinical studies of up to 12 weeks duration.(2)

"The complete data set for the Phase Ib study suggests that VX-950 is well-tolerated and can substantially reduce virus in a 14-day study," said Henk W. Reesink, M.D., Associate Professor of Medicine at Academic Medical Center in Amsterdam. "The results of the blood-concentration versus antiviral effect analysis are encouraging because they indicate that optimal antiviral response could be maintained if certain trough concentrations are achieved. Moreover, the viral kinetic analysis supports the evaluation of VX-950, at doses that maintain the target trough concentration, in a novel treatment paradigm of 12 weeks duration."

Phase Ib Study: Viral Sequencing Results In a further analysis planned for presentation on Monday, November 14, researchers used a novel sequencing approach to analyze the sequences of the HCV NS3 protease gene in samples isolated from patients prior to and following treatment in the Phase Ib study from all dose groups, including suboptimal dose groups.

The relative frequencies of wild-type and variant virus, as well as the sensitivity of variant protease enzymes to inhibition by VX-950 in vitro, were assessed and correlated with the viral load response obtained during dosing with VX-950. Three categories of HCV-RNA response were identified: continued decline (decline in HCV-RNA from day 1 through day 14), viral rebound (increase in HCV-RNA between nadir and day 14), and plateau response (minimal change in HCV-RNA between nadir and day 14). The patients with a continued decline in HCV-RNA had the highest mean trough VX-950 concentration, while the patients with viral rebound had the lowest mean trough blood concentrations. In the group of patients with continued viral decline on treatment, HCV- RNA levels at the end-of-dosing were below the limit of detection (less than 100 IU/mL) of the sequencing assay. At 7-10 days post-treatment, virus could again be isolated. In the post-treatment period, wild-type virus predominated, with some variants detected that displayed a minimally-reduced sensitivity to VX-950 in vitro.

In the other two groups of patients, sequence changes associated with reduced sensitivity to VX-950 in vitro were detected at the end-of-dosing, including some variants with moderately- to highly- reduced sensitivity to VX-950. However, these sequence changes also appeared to result in reduced viral fitness. In particular, the frequency of the variant (A156V/T) with the highest level of reduced drug sensitivity diminished markedly between the end-of-dosing and post-treatment analysis, indicating significantly reduced in vivo fitness relative to wild-type virus. Published in vitro data indicate that the A156V/T variant also retains sensitivity to interferon.(3)

"This is the first study that has attempted to comprehensively characterize HCV protease variants that may emerge during treatment with a potent direct-acting antiviral compound. As expected, selection of certain variants was associated with suboptimal drug levels and a suboptimal initial decline of HCV-RNA concentrations that led to either viral rebound or a plateau in viral response," said Christoph Sarrazin, M.D., Saarland University Hospital, Homburg, Germany, and Study Investigator. "It is encouraging that patients with the highest blood concentrations of VX-950 achieved continuous decline in viral load levels over the entire dosing period, suggesting that achieving sufficient trough concentrations could suppress the viral variants associated with viral rebound. Further, the sequencing results provide a strong rationale for the combination of VX-950 and pegylated interferon to achieve optimal response rates."

Additional Data Presentations Two additional abstracts related to VX-950 will be presented at the conference. In one abstract, researchers showed that despite heterogeneity among viral sequences that could be isolated from patients prior to treatment, all isolates were sensitive to VX-950 in vitro. Minor viral variants that may have existed at a frequency of less than 2 percent would not have been detected with the approach utilized.(4) In another abstract, researchers found that patients receiving VX-950 in the Phase Ib study rapidly achieved substantial reductions in alanine aminotransferase (ALT) levels after 14 days of treatment. In addition, changes in median neopterin levels correlated with decreases in HCV-RNA and ALT during administration of VX-950, suggesting that inhibition of HCV replication by VX-950 may decrease inflammation and tissue damage.(5)

Clinical and Regulatory Milestones Vertex recently announced the initiation of a 14-day Phase Ib combination study of VX-950 and pegylated interferon in Europe, using a new tablet formulation that is expected to achieve significantly higher blood concentrations compared to the oral suspension formulation used previously. Today, Vertex announced the filing of an IND to support Phase II clinical development of VX-950. Vertex also affirmed today that it remains on track to initiate by year-end a 28-day, Phase II combination study of VX-950 and pegylated interferon.

About Hepatitis C Hepatitis C is a liver disease caused by the hepatitis C virus, which is found in the blood of people with the disease. HCV, a serious public health concern affecting 3.4 million individuals in the United States, is spread through direct contact with the blood of infected people. Though many people with hepatitis C may not experience symptoms, others may have symptoms such as jaundice, abdominal pain, fatigue and fever. Hepatitis C significantly increases a person's risk for developing long-term infection or chronic liver disease. It also increases a person's risk of developing cirrhosis and of dying from a long-term infection.

About VX-950 VX-950 is an oral inhibitor of hepatitis C virus protease, an enzyme essential for viral replication. Vertex researchers were the first to solve the three-dimensional crystal structure of HCV protease, and have used structural insights to enable the design of small molecule HCV protease inhibitors, including VX-950. The VX04-950-101 clinical study being reported at AASLD was a dose-range finding study that included three panels of eight healthy subjects each (Part A) and three panels of 12 patients with genotype-1 HCV (Part B). In Part A, subjects were dosed for five days at doses of 450 mg, 750 mg or 1250 mg every eight hours, or placebo. Data from Part A were reported in May 2005 at the Digestive Disease Week meeting. In Part B, patients were dosed for 14 days at doses of 450 mg or 750 mg every eight hours, or 1250 mg every 12 hours or placebo. The objectives of the study were to assess safety, tolerability and antiviral activity in patients with HCV.

About Vertex Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is principally focused on viral diseases, inflammation, autoimmune diseases and cancer. Vertex co-promotes the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.

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November 19, 2005

Pill Form of Therapy for HCV Coming Closer

This report is an update of therapy progress presented at the AASLD (American Academy for the Study of Liver Diseases).

Three separate approaches are covered.

Yes, progress is being made.

AidsMap, November 18, 2005

Liz Highleyman

The latest data on three experimental hepatitis C drug candidates were presented at the American Association for the Study of Liver Diseases meeting, held November 11-15 in San Francisco. Current standard treatment for hepatitis C is based on interferon, an injected cytokine that stimulates immune response. In contrast, several investigational oral agents work by directly targeting the hepatitis C virus, similar to antiretroviral agents used to treat HIV.

Valopicitabine
Christopher O’Brien from the University of Miami presented the first interim data from an American Phase IIb trial of valopicitabine, or NM283, a nucleoside analogue hepatitis C polymerase inhibitor being developed by Idenix Pharmaceuticals.

The study included 190 patients randomly assigned to receive 800mg valopicitabine monotherapy, one of three doses (400mg, ramped dosing from 400 to 800mg, or 800mg once daily) of valopicitabine plus pegylated interferon alpha-2a (Pegasys) 180mg/week, or pegylated interferon plus ribavirin 1000-1200mg daily; 152 participants completed 12 weeks of treatment. Baseline characteristic were similar in the five arms, with a mean age of about 50 years. By ethnicity, 51-76% were Caucasian, 10-23% were East Asian, 10-23% were Middle Eastern or Indian, and fewer than 2% were African-American.

All were previous non-responders who did not clear hepatitis C with twelve weeks or more of pegylated interferon plus ribavirin, the standard treatment for HCV infection; relapsers were excluded. All had genotype 1 hepatitis C, baseline hepatitis C RNA of at least 100,000 copies/ml, and compensated liver disease.

After twelve weeks, patients in the two higher-dose valopicitabine combination arms achieved significantly greater suppression of hepatitis C RNA compared with the pegylated interferon/ribavirin arm. Hepatitis C viral load declined by 0.78 log10 copies/ml in the valopicitabine monotherapy arm, 1.92 log10 copies/ml in the pegylated interferon/ribavirin arm, 2.22 log10 copies/ml in the 400 mg valopicitabine combination arm, 2.51 log10 copies/ml in the in 400-800 mg valopicitabine combination arm, and 2.77 log10 copies/ml in the 800mg valopicitabine combination arm (p=0.001 for the latter two arms compared with pegylated interferon/ribavirin).

Percentages achieving early virological response (at least a 2-log reduction in hepatitis C virus RNA at twelve weeks) were 5%, 41%, 54%, 71%, and 63%, respectively (p < 0.001 for the latter two arms compared with pegylated interferon/ribavirin). In the 400-800 and 800mg valopicitabine combination arms, 21% achieved at least a 4-log drop in hepatitis C virus RNA compared with 6% in the pegylated interferon/ribavirin arm (p=0.05). Valopicitabine was safe and generally well tolerated, with no dose-limiting adverse events. Among the 50 participants observed for six months, no viral breakthrough or resistance has been detected. “These are promising results, particularly for the many treatment-refractory patients in urgent need of new therapeutic options,” O’Brien concluded.

SCH503034
Stefan Zeuzem from Saarland University Hospital in Homburg, Germany, reported on a Phase Ib study of Shering-Plough’s NS3 serine protease inhibitor, SCH503034. In this international multicentre trial, 61 patients were randomly assigned to receive one of four different schedules of SCH503034 (100, 200, or 400mg twice daily or 400mg three times daily), or placebo, for 14 days. Baseline characteristics were similar across the arms, with a mean age of about 50 years. All patients were non-responders to prior treatment with pegylated interferon plus ribavirin (less than 2-log reduction in hepatitis C virus RNA after twelve weeks of treatment) and had genotype 1 hepatitis C. Participants had baseline hepatitis C viral loads of at least 30,000 copies/mL, mean ALT levels of 82-112 IU/L, and compensated liver disease.

SCH503034 was rapidly absorbed, reaching a maximum concentration at 1-2 hours post-dosing. The most pronounced reduction in hepatitis C viral load was seen in the 400mg three times daily arm, with a mean maximum decline of 2.06 log10 copies/ml from baseline (range 1.1-2.7 log10 copies/ml). The magnitude of hepatitis C viral load reduction was positively correlated with SCH503034 trough level. Participants in all three twice-daily arms experienced smaller hepatitis C viral load decreases than seen in the three times daily group, but still did better than the placebo arm. Sixty percent of patients in the 400mg three times daily arm achieved a maximum hepatitis C viral load reduction of more than 2 log10 copies/ml, compared with 18%, 17%, and 8%, respectively, in the 400mg, 200mg, and 100mg twice daily arms. Conversely, no patient in the 400mg three times daily group had less than a 1-log viral load decrease, compared with 18%, 50%, and 67%, respectively, in the 400mg, 200mg, and 100mg twice daily arms. ALT reduction corresponded with viral load decreases.

Zeuzem also presented data from a second small trial showing that SCH503034 exhibited promising antiviral activity when combined with pegylated interferon in previous non-responders. In this open-label crossover study, all participants received 200 or 400mg SCH503034 monotherapy for seven days, pegylated interferon alpha-2b (Peg-Intron) 1.5 mcg/kg/week for 14 days, and SCH503034 plus pegylated interferon for 14 days, but in different orders (i.e., some started with SCH503034 alone, some with pegylated interferon alone, and some with the combination). The mean hepatitis C viral load decrease was more than 2 log10 copies/ml in both the 200mg and 400mg SCH503034 combination arms, compared with 1 log10 copies/ml in the pegylated interferon monotherapy arm; 40% of patients (4 out of 10) in the 400mg arm achieved undetectable hepatitis C viral load, compared with none of those receiving only pegylated interferon. Zeuzem concluded that combination therapy produced at least an additive decline in HCV RNA.

In both studies, SCH503034 appeared self and well-tolerated at all dose levels. In the monotherapy study, adverse events were mild and similar in the SCH53034 and placebo arms. The adverse event profiles in the second study were similar in the SCH503034 and combination therapy arms, consisting mostly of well-known pegylated interferon side effects. Importantly, in animal and human studies to date, researchers have seen no clinical or histopathological evidence of the type of cardiac toxicity that led to the discontinuation of an earlier hepatitis C protease inhibitor, BILN-2061. While one patient did develop the V170A mutation (shown to cause resistance to SCH503034 in laboratory studies), no phenotypic resistance was observed and no viral rebound was seen during treatment in the 400mg three times daily arm. Phase II studies assessing 24 and 48 week VX-950/pegylated interferon combination therapy are underway.

VX-950
Finally, Henk Reesink from the Academic Medical Centre in Amsterdam reported data from a Phase Ib dose-ranging trial of a second hepatitis C protease inhibitor, VX-950 (Vertex Pharmaceuticals). This study included 36 individuals with genotype 1 hepatitis C, mostly prior non-responders, but also a few treatment-naive patients. Participants were assigned to receive either placebo or an oral suspension of VX-950 as monotherapy, 450 or 750mg every 8 hours (three times daily) or 1250mg every twelve hours (twice daily), for 14 days. Here, too, baseline characteristics were generally similar across the study arms.

Participants in all VX-950 dose groups showed steep declines in hepatitis C during the first two-to-three days of treatment. All patients receiving VX-950 experienced at least a 2-log viral load decrease from baseline. Most individuals in the three VX-950 arms (26 out of 28) had a maximum hepatitis C viral load decrease of at least 3 log10 copies/ml, and four patients had a greater than 5-log decrease. The 750mg three times daily dose produced the highest VX-950 trough levels and the largest mean HCV RNA decrease: 4.4 log10 copies/ml, or a 25,000-fold reduction. Four patients in this arm had undetectable viral load (below 30 IU/mL) at the end of the treatment period. Hepatitis C viral load also decreased in the other two dose groups, but started to climb again after seven days. VX-950 appeared to work as well in prior non-responders as in naive patients. ALT levels declined during treatment in all dose groups. There were no severe adverse events, dose reductions, or treatment discontinuations. The most commonly reported side effects (headache and diarrhoea) occurred with similar frequency in the VX-950 and placebo arms. As with SCH503034, no cardiotoxicity was observed.

In a companion resistance study presented by Christoph Sarrazin, also from Homburg, researchers sequenced the HCV NS3 gene from 34 patients at baseline, day 14, and day 21-24. Several variants were seen with reduced sensitivity to VX-950, at amino acid positions 36, 54, 155, and 156. A single V36 change conferred minimal resistance, while A156V/T was associated with high-level resistance. These mutations were detected in patients who experienced hepatitis C viral load rebound or plateau rather than continued decline. Variants with reduced sensitivity to VX-950 also had decreased replicative fitness, allowing wild-type hepatitis C virus to re-emerge after treatment discontinuation.

According to Reesink, VX-950 produced “the most rapid and dramatic response” seen to date with a single agent. Based on viral kinetic analysis, he suggested that the drug may reduce hepatitis C to undetectable levels in approximately 12 weeks - substantially shorter than the standard 48 week therapy for genotype 1 hepatitis C. Based on data collected so far, Vertex filed an investigational new drug application with the U.S. Food and Drug Administration on November 11. A 14-day Phase Ib study of a new tablet formulation of VX-950 in combination with pegylated interferon is underway in Europe, and a 12 week combination study is planned for next year.

While all three of these experimental agents look promising, it is too soon to say whether they will ultimately produce sustained virological response. Nevertheless, based on research to date, many experts believe antiviral drugs - potentially in combination regimens consisting entirely of oral agents - are the wave of the future for hepatitis C therapy.

References

O’Brien C. et al. Randomized trial of valopicitabine (NM283), alone or with peg-interferon, vs. retreatment with peg-interferon plus ribavirin (PegIFN/RBV) in hepatitis C patients with previous non-response to PegIFN/RBV: first interim results. 56th Annual Meeting of the American Association for the Study of Liver Diseases, San Francisco, abstract 63186, 2005.

Reesink H. et al. Final results of a phase 1B, multiple-dose study of VX-950, a hepatitis C virus protease inhibitor. 56th Annual Meeting of the American Association for the Study of Liver Diseases, San Francisco, abstract 62580, 2005.

Sarrazin C. et al. Characterization of viral variants in the HCV NS3 protease domain of genotype 1 patients that are selected during 14 days of dosing with VX-950. 56th Annual Meeting of the American Association for the Study of Liver Diseases, San Francisco, abstract 72562, 2005.

Zeuzem S. et al. Anti-viral activity of SCH 503034, a HCV protease inhibitor, administered as monotherapy in hepatitis C genotype-1 (HCV-1) patients refractory to pegylated interferon (Peg-IFN-a). 56th Annual Meeting of the American Association for the Study of Liver Diseases, San Francisco, abstract 67484, 2005.

Zeuzem S. et al. Combination therapy with the HCV protease inhibitor, SCH 503034, plus PEG-Intron in hepatitis C genotype-1 PEG-Intron non-responders: phase Ib results. 56th Annual Meeting of the American Association for the Study of Liver Diseases, San Francisco, abstract 67627, 2005.

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November 11, 2005

HCV Vaccine Progress

The development of a HCV vaccine is very exciting, even to patients already infected. Although the vaccine will not help them direcly, it shows definite progress in understanding and outsmarting this virus that is known to be difficult to combat due to its rapid mutation.

If they are making progress with a vaccine, progress for better treatment must be close behind.

Major Milestone Reached In Hepatitis C Vaccine Program
Select Vaccines (AUSTRALIA)
November 11, 2005

11 November 2005: Melbourne-based biotechnology company, Select Vaccines Ltd (ASX:SLT), today announced positive results from its first pre-clinical studies of a potential vaccine against hepatitis C.

The results followed nine months of animal studies and represent a major advancement of the hepatitis C vaccine program.

Managing Director of Select Vaccines, Dr Martin Soust, said "We obtained good results in our early studies in the laboratory and in a pilot study and, on the strength of these results, we initiated a dose ranging study in mice."

"We observed very strong immune responses after just one small dose of less than one microgram of this hepatitis C vaccine," said Associate Professor David Anderson, Chief Scientific Officer with Select Vaccines.

Hepatitis C specific antibodies were produced by all 46 animals injected with the hepatitis C vaccine, even at the lowest dose studied which was 0.2 micrograms. There was also the induction of significant levels of hepatitis C specific T cells, which suggests the vaccine may promote better overall control of infection.

An immune response of this strength in mice suggests a very strong likelihood that a similarly strong response will be produced in a larger animal species that will be studied in the next round of investigations.

The results exceeded the company's expectations and suggest that the prospects of developing a human vaccine with a good safety profile are excellent.

"The commercial potential of a vaccine against hepatitis C is substantial. Globally, there are almost 300 million people currently infected with hepatitis C and up to 10 million new infections each year. The market for a vaccine against hepatitis C has been estimated to be worth more than $US500 million. The company is pursuing the development of this vaccine as there is currently no vaccine available" said Dr Soust.

"The next steps in our hepatitis C vaccine program are very clear," Anderson said. "We plan to undertake further studies in larger animals and to produce purified injectable material under GLP conditions for use in a preclinical toxicology study before moving into a phase I clinical trial." Professor Anderson explained.

Select Vaccines is developing the hepatitis C vaccine with its proprietary vaccine technology that employs virus-like particles to generate a protective immune response against infection. The platform technology involves producing virus-like particles into which specific vaccine antigens of interest, in this case an envelope protein from hepatitis C virus, have been inserted.

"We have been waiting for the outcome from these initial animal studies before considering a very substantial longer-term commitment to vaccine development. With this proof of the VLP platform in hand we have a very strong indication that we may be able to develop vaccines against other infectious diseases and we will look to accelerate and expand our work accordingly." said Dr Soust.

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October 19, 2005

Japanese Researchers Make Progress

This article is from one of the largest Japanese newspapers. As it shows, researchers in Japan are also working hard to develop a better treatment for HCV.

Scientists the world over are doing their best to find a less toxic and more effective treatment.

Possible breakthrough on hepatitis C
10/18/2005

The Asahi Shimbun

A Japanese research team said it has found a method that prevents the multiplication process of the virus for hepatitis C, a chronic disease that could lead to fatal disorders like cirrhosis and liver cancer.

The method deals with cells infected with the virus, not the virus itself, meaning that drugs could be developed to stop the multiplication process while preventing the virus from becoming resistant.

It is still unknown how exactly the hepatitis-C virus (HCV) multiplies once inside human cells. But researchers know that once the virus enters the cell, it develops a platform for multiplication by combining itself with a certain lipid, an organic compound.

The team at Chugai Pharmaceutical Co., led by Masayuki Sudo, determined a point inside cells where the HCV combines itself with the lipid.

Without the platform, the HCV is unable to duplicate itself, the researchers said.

Using human liver cells, the team added a substance to the lipid that prevented it from combining with the HCV. Thus, the platform for multiplication could not synthesize, the researchers said.

"If we can target the mechanism of virus-infected cells, it could prompt the development of more effective drugs," Sudo said.

The team's report was to be published on the Web site of the U.S. science journal Nature Chemical Biology on Monday.

An estimated 1 million to 2 million are infected with hepatitis C in Japan.

"HCV is troublesome because of its many mutations," said Takaji Wakita, a senior researcher at the Tokyo Metropolitan Institute for Neuroscience. "If we can target something that is contained in the cells, we may be able to come up with drugs that would prevent the virus from developing resistance. We need to make sure of the side effects, including the possibility that the treatment could affect other cells."(IHT/Asahi: October 18,2005)

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October 05, 2005

VX-950 Making Progress

Here's an exciting one, VX-950 we've been watching for a while. This protease inhibitor is making good progress (and is orally administered, no less).

While being studied as another Interferon treatment enhancer, it could be very helpful if it replaced Ribavirin. We understand Ribavirin is what causes the most toxic responses to current therapy.

New Data Suggest Vertex's Oral Hepatitis C Virus Protease Inhibitor VX-950 May Reduce Liver Injury; VX-950 Clinical Milestones on Track

MONTREAL, Oct. 3 /CNW/ -- New data show that patients with genotype 1 hepatitis C virus (HCV) infection treated with VX-950, an investigational oral HCV protease inhibitor being developed by Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX), rapidly achieved substantial reductions in alanine aminotransferase (ALT) levels after 14 days of treatment.

The findings were presented today by researchers at the 12th International Symposium on Hepatitis C and Related Viruses (HCV 2005) in Montreal, Canada. Vertex also provided an update on clinical development of VX-950, which is one of the most advanced of a new class of medicines in development for the treatment of chronic hepatitis C infection.

Data from a 14-day clinical study demonstrated that treatment with any one of three doses of VX-950 resulted in median serum ALT declines of 25-32 U/L in all dose groups. In the placebo group, a median 8 U/L increase was observed.

Prior to treatment with VX-950, serum ALT levels were elevated in approximately 70 percent of patients in the study. In the VX-950 dose groups, 83 percent (15 of 18) of patients with elevated ALT levels at baseline (prior to treatment) had achieved normalization of ALT levels at day 14, compared to 0 percent (0 of 6) in the placebo group.

Elevated ALT levels are common in HCV patients and are considered to be a marker of liver injury due to HCV infection. Mean levels of serum neopterin also were observed to decrease with VX-950 treatment in the study. Decreased neopterin levels may be a further signal of a reduction in inflammation associated with HCV infection.(1)

A study of viral isolates from patients at baseline in a 14-day clinical study, also presented at the conference, found heterogeneity among viral sequences in the HCV protease domain. In vitro analysis indicated that all baseline viral isolates were sensitive to VX-950.(2)

"To date, data from early clinical studies have suggested that VX-950 is well-tolerated and can rapidly reduce HCV viral levels in patients over a short treatment period," said John Alam, M.D., Senior Vice President of Drug Evaluation and Approval at Vertex. "In addition, we now have evidence that treatment with VX-950 appeared to lead to a dramatic decline in markers of liver injury associated with viral infection."

Clinical Update Vertex affirmed today that it remains on track to achieve key milestones in its VX-950 clinical program in the fourth quarter of 2005, including initiation of a 14-day Phase Ib combination study of VX-950 and pegylated interferon in Europe and filing of an investigational new drug (IND) application in the United States to support Phase II development of VX-950. Vertex anticipates that it will initiate a 28-day, Phase II combination study of VX-950 and pegylated interferon by year-end. Vertex expects to present additional VX-950 clinical data at two more medical conferences in the fourth quarter of 2005.

Clinical Need and Market Opportunity in HCV Infection

Chronic hepatitis C virus (HCV) infection is a serious public health concern affecting approximately 2.7 million people in the United States. HCV causes inflammation of the liver, which may lead to fibrosis and cirrhosis, liver cancer, and ultimately, liver failure. Cirrhosis of the liver resulting from chronic HCV infection is the leading reason for liver transplantation in the U.S. Due to the asymptomatic nature of HCV infection, it often goes undetected for up to 20 years following initial infection. Worldwide, the disease afflicts as many as 170 million people. Each year, 8,000 to 10,000 people in the U.S. die from complications of HCV infection.

About Vertex

Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is principally focused on viral diseases, inflammation, autoimmune diseases and cancer. Vertex co-promotes the HIV protease inhibitor, Lexiva(R), with GlaxoSmithKline.

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October 01, 2005

Another Biotech Contender

Here is another compound from a biotech pharmaceutical company. This antisense approach has been spoken of with great promise. We look forward to seeing how it proceeds. We'll stay tuned to this one...

AVI BioPharma Initiates Hepatitis C Clinical Trial

PORTLAND, Ore.--(BUSINESS WIRE)--Sept. 28, 2005--AVI BioPharma, Inc. (Nasdaq:AVII), today announced the initiation of an exploratory safety and efficacy clinical trial using its proprietary NEUGENE(R) antisense compound AVI-4065. The multicenter study will assess the safety, tolerability, pharmacokinetics and viral response to daily subcutaneous administration of AVI-4065 among healthy volunteers and patients with chronic active hepatitis C virus (HCV).

"There is a large, unmet medical need for effective HCV treatments, as the current treatment regimen is successful in less than half of the patients infected with genotype 1 HCV, the most common form of the virus in the U.S.," said Denis R. Burger, Ph.D., chief executive officer of AVI. "In addition, the de facto treatment regimen of nonspecific antivirals pegylated interferon and ribavirin is expensive, has a plethora of side effects, and is not well tolerated by many patients. The ability of our NEUGENE antisense to specifically target the HCV virus may offer a safer and more efficacious drug for patients."

The multicenter clinical trial will include 80 subjects: 40 healthy adult volunteers in the first phase of the study and 40 patients with chronic active HCV in the second phase. In the first phase, up to four dosage levels will be evaluated to confirm the safety of desired serum drug levels. In the second phase, 40 patients with chronic active HCV will be enrolled, including patients who are drug-naive and patients who have failed conventional interferon and ribavirin treatment. This phase of the trial will assess the safety, tolerability, pharmacokinetics, biological responses and HCV virological effects of AVI-4065 over a minimum of 14 days of treatment. Patients will be monitored following treatment to assess a sustained HCV virological response to AVI-4065.

Mark Holodniy, M.D., F.A.C.P., professor of medicine at Stanford University School of Medicine and director of the Department of Veterans Affairs Public Health Research & Consultation Program located at the Veterans Affairs Palo Alto Health Care System in Palo Alto, Calif., will serve as the principal investigator for the trial. Dr. Holodniy said, "I am pleased to participate as an investigator at one of many study sites in the rigorous clinical testing of AVI's lead compound targeted for the HCV virus. The study should provide a better understanding of the compound's safety, pharmacokinetics, and potential biological effects against HCV."

HCV is a single-stranded RNA virus. Because HCV and other single-stranded RNA viruses have relatively simple genetic structures, they are attractive targets for AVI's NEUGENE antisense, which is designed to target conserved portions of the viral genetic code that are not likely to mutate over time.

About Hepatitis C

Chronic HCV infection causes an inflammation of the liver that can result in the development of cirrhosis, liver cancer or liver failure. According to the World Health Organization, approximately 170 million people worldwide are chronically infected with HCV. It is the most common chronic blood-borne infection in the developed world and the leading cause of liver transplants in the United States. The CDC estimates that approximately 3.9 million Americans have been infected with HCV, of whom 2.7 million are chronically infected.

The Hepatitis Foundation International estimates that between 8,000 and 10,000 people die annually in the United States from HCV-related cirrhosis or liver cancer. The current treatment for HCV, 24 to 48 weeks of therapy with pegylated interferon alpha and ribavirin, is successful in less than half of the patients infected with genotype 1 HCV, the most common form of the virus in the U.S. Furthermore, this treatment has numerous side effects, some of them severe, which make it difficult for almost half of initially treated patients to tolerate the recommended dosages and duration of treatment.

About AVI BioPharma

AVI BioPharma develops therapeutic products for the treatment of life-threatening diseases using third-generation NEUGENE antisense drugs. AVI's lead NEUGENE antisense compound is designed to target cell proliferation disorders, including cardiovascular restenosis, cancer and polycystic kidney disease. In addition to targeting specific genes in the body, AVI's antiviral program uses NEUGENE antisense compounds to combat disease by targeting single-stranded RNA viruses, including West Nile virus, hepatitis C virus, dengue virus and Ebola virus. More information about AVI is available on the company's Web site at http://www.avibio.com.

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September 28, 2005

Zandaxin Announcement December 2005

Phase 3 Trials are very advanced. If it works, Zandaxin is another enhancement for Interferon therapy. We are looking forward to alternatives to Interferon therapy, but this could be a very positive advance for patients who would consider Interferon and benefit from it. Especially considering that these tests are focused on non-responders, who currently have little recourse but to protect and support their livers with clinically proven natural approaches like Maximum Milk Thistle or Sho-saiko-to.

SciClone to Report Top-Line Data From First U.S. Hepatitis C Phase 3 Trial by Mid-December 2005

SAN MATEO, CA -- (MARKET WIRE) -- 09/27/2005 -- SciClone Pharmaceuticals (NASDAQ: SCLN) today announced that it expects to unblind and report top-line data by mid-December 2005 from the first of its two U.S. phase 3 hepatitis C virus (HCV) clinical trials evaluating its lead compound, ZADAXIN®, as a novel adjunctive treatment for hepatitis C patients who have failed prior therapy. Previously, SciClone planned to unblind the data from both trials together and report these data in the early part of 2006.

"Earlier access to the results from the first trial will provide us with valuable information for the design, prioritization and implementation of additional product development programs, ZADAXIN regulatory plans, marketing strategy and resource allocations," commented Dr. Ira Lawrence, President and Chief Executive Officer of SciClone Pharmaceuticals, Inc. "SciClone is at a very important point in its history, with final data from this first phase 3 trial available to us by mid-December of this year, as well as preliminary data from a phase 2 malignant melanoma trial run by Sigma-Tau by year-end and final data from the second HCV phase 3 trial released in the early part of 2006."

SciClone's two phase 3 hepatitis C trials are designed to determine the benefit of adding ZADAXIN to pegylated interferon alpha to treat hepatitis C non-responder patients. Complementary in design, the first trial enrolled over 500 HCV non-responder patients without liver cirrhosis, while the second trial enrolled over 500 HCV non-responder patients with early liver cirrhosis. Patients in the second trial have completed therapy and will finish their observation period in December 2005. Biopsies for the last patients enrolled in this second trial will be performed by the end of February 2006 and the data from this trial will be reported in the early part of 2006.

"Of course, at this time we cannot predict whether the results from either trial will be favorable or unfavorable," cautioned Dr. Lawrence. "In general, favorable results from both trials would be needed to proceed with the filing of an NDA."

SciClone's two U.S. phase 3 clinical trials are multi-center, randomized and double-blinded studies. All patients in each trial are assigned to a 48-week course of treatment of either ZADAXIN and pegylated interferon alpha or placebo and pegylated interferon alpha. After completing treatment, the patients are followed for a 24-week observation period. The primary endpoints of both trials are the achievement of a sustained virologic response (SVR), defined as the lack of detectable HCV RNA in the bloodstream measured by PCR test 24 weeks after the completion of 48 weeks of therapy, and improvement in liver histology.

About SciClone

SciClone Pharmaceuticals is a biopharmaceutical company engaged in the development of therapeutics to treat life-threatening diseases. SciClone's lead product ZADAXIN® is currently being evaluated in two phase 3 hepatitis C clinical trials in the United States and one hepatitis C triple therapy clinical trial in Europe. ZADAXIN also is being evaluated in other late-stage clinical trials for the treatment of hepatitis B and certain cancers. The company's other principal drug development candidate is SCV-07, currently in phase 1 development, which is being evaluated for the treatment of viral and other infectious diseases. For more information about SciClone, visit www.sciclone.com.

The information in this press release contains forward-looking statements including our expectations regarding the timing of availability of clinical trial data. Words such as "expects," "plans," "believe," "may," "will," "anticipated," "intended" and variations of these words or similar expressions are intended to identify forward-looking statements. Actual results could differ materially and adversely from those expressed in any forward-looking statements as a result of various factors, including unexpected difficulties in compiling or analyzing data, and the availability of information from third parties. as well as other risks and uncertainties described in SciClone's filings with the Securities and Exchange Commission. The availability of phase 3 trial data, even positive data, by itself, does not ensure that the company can successfully file an NDA or ultimately attain regulatory approval.

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New Drug, Actilon, In Development

Another new approach in the pipeline. As We've always said, with millions of people infected, the drug and biotech companies are falling over each other to come up with viable treatments to improve on what is currently available.

NEW YORK, Sept 27 (Reuters) - Coley Pharmaceutical Group Inc. (COLY.O: Quote, Profile, Research) on Tuesday said it is starting an early-stage clinical trial of an experimental drug to treat chronic Hepatitis C virus.

Coley expects preliminary data from the Phase Ib study of the drug, Actilon, to be available in the second half of 2006.

The study will involve 60 patients infected with the virus, who will be divided into different treatment groups over a period of three months. Some patients will take only Actilon, some will take it in combination with one or two standard treatments, and some will take standard treatments without Actilon.

The company, which went public last month, has also attracted attention because of three other promising experimental drugs, especially ProMune, which is entering late-stage trials against non-small cell lung cancer. Coley, based in Wellesley, Massachusetts, is developing that product with Pfizer Inc. (PFE.N: Quote, Profile, Research)

Its drugs are designed to stimulate the immune system by acting on proteins called Toll-like receptors. Actilon acts through the Toll-like receptor 9 found in dendritic cells and B cells, which are mainstays of the immune system.

Shares of Coley were up $1.52, or 9.4 percent, to $17.64 on Nasdaq. (Additional reporting by Ransdell Pierson)

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September 14, 2005

Another Treatment Development Alliance

Sometimes business journals contain valuable information about emerging hepatitis C therapies. Given the fact Stanford University is involved in this venture (and the companies involved are putting up pretty big bucks), this is another one to watch closely.

We'll keep you posted.

September 13, 2005

Alnylam to align with West Coast firm on hep C treatment

Boston Business Journal

Alnylam Pharmaceuticals Inc. and a California company have signed a joint licensing deal for a gene that could help treat hepatitis C.

The Cambridge, Mass. company (Nasdaq: ALNY) and Isis Pharmaceuticals Inc. of Carlsbad (Nasdaq: ISIS) announced on Tuesday that they inked a combined licensing agreement with Stanford University.

They'll gain co-exclusive access to Stanford research regarding a MicroRNA gene found to be needed to replicate the hepatitis C virus in mammalian cells.

Researchers hope the discovery could lead to treatments for hepatitis C, a viral infection of the liver that can cause cirrhosis and liver cancer. Researchers estimate 170 million people globally have hepatitis c infections. Vaccines don't exist yet to prevent the disease.

Alnylam announced on Sept. 7 that it had signed a multi-year alliance with Novartis AG that could be worth more than $700 million if the deal produces commercial products.

Alnylam and Novartis (NYSE: NVS) will work on developing RNAi therapies. RNAi is a natural process within cells that selectively silences genes, and Alnylam believes RNAi can treat disease by silencing genes that cause disease.

In the short term, Novartis will pay Alnylam $56.8 million, through cash and a purchase of 4.2 shares of Alnylam common stock.

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August 24, 2005

TLR7 Agonist against HCV

Wow. Another promising candidate for more effective (and less toxic) HCV treatment.

We'll keep you posted on this one, as well as any others coming down the pipeline.

Be sure to notice this excerpt:

"Worldwide sales for HCV products were an estimated $2.7 billion in 2003, yet current treatments for HCV may be ineffective in up to 50 percent of patients, and many treatments are associated with serious side effects."

That $2.7 billion was in 2003 (it would be more now). This amount is what keeps drug companies looking for a better treatment.

Also notice they are estimating current therapies may be ineffective in up to 50% of patients. Compare that to the numbers your doctor is giving you.

This is part of the reason you need to stay informed.

Peer Reviewed Report in HEPATOLOGY Details Inhibition of Hepatitis C Virus and Immune Activation by a TLR7 Agonist

SAN DIEGO, Aug. 23 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS), reported the publication of the results of a Phase IB clinical trial of isatoribine (ANA245) in HEPATOLOGY(1), the official journal of the American Association for the Study of Liver Disease (http://www3.interscience.wiley.com/cgi-bin/abstract/111081950/ABSTRACT).

This peer-reviewed publication concluded that isatoribine treatment resulted in biological activity and a statistically significant antiviral effect with relatively few and mild side effects. "The manuscript describes the encouraging combination of good tolerability with desirable immunologic and anti-HCV activity that we observed for isatoribine," said Yves Horsmans, M.D., Professor at Cliniques Universitaires St. Luc in Brussels and Principal Investigator of the study. "These results create strong interest in clinical evaluation of ANA975, the oral prodrug form of isatoribine that now is being jointly developed by Anadys and Novartis." The Phase IB clinical trial was designed to test the safety and tolerability of isatoribine in patients chronically infected with HCV.

The study was a dose-escalating, open-label evaluation of isatoribine administered intravenously at 200 mg, 400 mg, 600 mg and 800 mg doses to 32 adults, most of whom received once daily dosing for seven days. The trial was conducted at two clinical centers in Western Europe. Patients participating in the study were either HCV-treatment naive or were partial responders to or relapsed from interferon-alpha, a component of the current standard of treatment. Study results showed that isatoribine demonstrated dose-dependent changes in immunologic biomarkers. The amount of HCV in the bloodstream, or plasma viral load, was significantly reduced in patients receiving 800 mg once daily for seven days.

Of the 12 patients in this 800 mg dose group, 10 were infected with HCV genotype 1, which is considered difficult-to-treat with current therapies. Isatoribine treatment was safe and well tolerated in the study, with no serious adverse events and a low frequency of side effects, although definitive conclusions regarding product safety cannot be made until the results of future clinical trials of longer duration in more patients are known. No patient altered isatoribine treatment or withdrew from the study due to adverse events or clinical laboratory abnormalities.

About Hepatitis C

Hepatitis C virus, the most common chronic blood-borne infection in the United States, causes inflammation of the liver and may progress to more serious complications such as cirrhosis of the liver, liver cancer and death. Approximately 2.7 million people in the United States are chronically infected with HCV, and the Centers for Disease Control (CDC) estimates that by the year 2010, the number of deaths attributed annually to HCV could surpass that due to HIV/AIDS.

Worldwide sales for HCV products were an estimated $2.7 billion in 2003, yet current treatments for HCV may be ineffective in up to 50 percent of patients, and many treatments are associated with serious side effects.

About Anadys Anadys Pharmaceuticals, Inc. (http://www.anadyspharma.com) is a biopharmaceutical company committed to advancing patient care by discovering, developing and commercializing novel small molecule medicines for the treatment of hepatitis C virus (HCV), hepatitis B virus (HBV) and other serious infections. The Company has core expertise in Toll-Like Receptor-based small molecule therapeutics and structure-based drug design coupled with medicinal chemistry. Anadys' clinical development programs include ANA975 for the treatment of HCV and HBV, and ANA380 for the treatment of HBV. In addition, Anadys' therapeutic platform is designed to advance a strong and continual pipeline of drug candidates into the clinic.

1. Horsmans Y, Berg T, Desager J-P, Mueller T, Schott E, Fletcher SP, Steffy KR, Bauman LA, Kerr BM & Averett DR. "Isatoribine, an Agonist of TLR7, Reduces Plasma Virus Concentration in Chronic Hepatitis C Virus Infection". Hepatology 2005; 42:724-731.

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August 19, 2005

Vertex Advances on VX-950

Vertex has really been getting a positive roll on its clinical studies for VX-950 so far. It may be the first of a new generation of Hepatitis c therapies to hit the market, and that has investors very excited. Not to mention patients.

Vertex hits new 52-week high on upgrade

AUG. 19 11:43 A.M. ET

Shares of Vertex Pharmaceuticals Inc. jumped over 15 percent and set a new 52-week high Friday following an upgrade from investment firm JPMorgan over growing confidence for its early stage experimental hepatitis C treatment.

Vertex shares rose $2.60, or 15.9 percent, to $18.97, surpassing a former 52-week high of $18.14, in morning trading on the Nasdaq. Its stock has climbed from a 52-week low of $8.61 in April and surged in May as Vertex began releasing data from its early stage hepatitis C clinical trial. Company shares are up nearly 80 percent on the year.

JPMorgan upgraded Vertex to "Overweight" from "Neutral" in anticipation of additional safety data on the company's hepatitis C treatment VX-950 in the second half of 2005 and the initiation of mid-stage clinical trials for the drug.

Analyst Richard Smith said he believes favorable results will be replicated in upcoming mid-stage trials, and said VX-950 could potentially reduce treatment times of hard-to-treat patients. In May, the company released data showing that VX-950 decreased levels of hepatitis C genetic material within 14 days and was well-tolerated by the 34 patients enrolled in the study. "Our upgrade to Overweight is based on our increased conviction that VX-950 will be a successful product and that it represents a blockbuster opportunity for the company and the rest of the pipeline represents merely further upside if successful," Smith told investors in a research note.

The analyst also presented comparative data in his note showing that VX-950 caused the largest reduction of hepatitis C genetic material in patients out of a class of nine other experimental treatments being developed by other companies. Smith estimates the hepatitis C treatment market is heating up and may reach more than $8 billion in 2010.

Smith maintained his forecast of a loss per share of $1.86 for 2005, and improved his 2006 projection to a loss of $1.89 from a loss of $1.92. Analysts surveyed by Thomson Financial expect the company to post a loss per share of $1.76 in 2005 and $1.75 in 2006.

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August 16, 2005

Phase 1 Clinical Trial In Offing

Yet another treatment in the pipeline. But, this one is at the very beginning stages. They are still trying to discover whether it is even safe (let alone effective). Stay tuned...

Gilead and Achillion Announce Initiation of Phase I Clinical Trial Evaluating GS 9132 for the Treatment of Hepatitis C

FOSTER CITY, Calif. and NEW HAVEN, Conn.--(BUSINESS WIRE)--Aug. 15, 2005--Gilead Sciences (Nasdaq:GILD) and Achillion Pharmaceuticals today announced that the companies have begun dosing patients in a Phase I study of GS 9132, also known as ACH-806. Gilead and Achillion are investigating GS 9132 for the treatment of hepatitis C.

The Phase I trial is a double-blind, randomized, placebo-controlled dose-escalation study. The goal of the trial is to evaluate the pharmacokinetics, tolerability and safety of single escalating doses of GS 9132 in healthy volunteers. The study will take place in the United States and will enroll approximately 20 subjects.

In November 2004, Gilead and Achillion established an agreement granting Gilead worldwide rights for the research, development and commercialization of certain Achillion compounds for the treatment of hepatitis C. GS 9132 is a small molecule inhibitor of hepatitis C virus (HCV) replication, which works through a novel mechanism of action involving HCV protease. GS 9132 was discovered by Achillion, and the company completed the initial work necessary to move the compound into clinical development.

"Gilead and Achillion share a commitment to advancing novel compounds with the potential to address the unmet medical need that exists for patients chronically infected with hepatitis C," said Norbert Bischofberger, PhD, Executive Vice President, Research and Development, Gilead Sciences. "Achillion's leadership in the early clinical development of this compound, and work to ensure rapid progress toward the Investigational New Drug application filing earlier this summer, has allowed us to advance this important clinical program. We look forward to our continued collaboration."

"We are excited about the novel mechanism of action of GS 9132 involving HCV protease, and we are looking forward to establishing the safety profile of this compound in humans," stated Milind Deshpande, PhD, Chief Scientific Officer of Achillion. "Gilead has been a tremendous partner through the early part of our agreement and we look forward to benefiting from their clinical experience and building upon our relationship as Achillion brings GS 9132 through proof of concept studies."

About Hepatitis C

Hepatitis C is a viral liver disease, caused by infection with the hepatitis C virus. Globally, more than 170 million people have chronic hepatitis C. About three million Americans are now estimated to be chronically infected with HCV. Chronic hepatitis C is a leading cause of cirrhosis, a common cause of hepatocellular carcinoma, and is the leading cause of liver transplantation in the United States.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Australia.

About Achillion

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. The company's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. Achillion is focused on solutions for the most challenging problems in infectious disease -- HIV, hepatitis and resistant bacterial infections.

As an investigational compound, GS 9132 has not yet been determined safe or efficacious in humans for its ultimate intended use.

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August 13, 2005

Study Enrollment is Announced

This is a drug being developed in Canada in cooperation with Schering Plough. Seeing as Schering is currently the number two provider of Hepatitis c therapy this new compound must have quite a bit of credibility.

Of course, Schering may only be interested in this as an adjunct to interferon therapy, not a replacement for.

Migenix to test hepatitis C drug

Migenix has received authorization from Health Canada to begin a phase IIb combination study of MX-3253, a compound in development for the treatment of chronic hepatitis C virus infections.

12 Aug 2005, 08:50 GMT - Enrollment in the study is expected to commence in the next few weeks with results expected around mid- year 2006.

MX-3253 (celgosivir) is an alpha-glucosidase I inhibitor and is currently the only oral anti- hepatitis C virus (HCV) drug in development that acts through host-directed glycosylation. In preclinical studies, celgosivir has demonstrated strong synergy with interferon-alpha plus ribavirin suggesting it has the potential to be included as part of a combination therapeutic approach to improve efficacy.

Celgosivir is currently being evaluated in a phase IIa monotherapy study in treatment-naive and interferon-intolerant genotype I HCV patients with results of the study expected before the end of the third quarter of calendar 2005.

The phase IIb combination study of MX-3253 is a randomized, multi-center, active-controlled, 12 week evaluation of MX-3253 in three treatment arms of up to 20 chronic HCV patients each: celgosivir plus peginterferon alfa-2b plus ribavirin (three-way combination); celgosivir plus peginterferon alfa-2b (two-way combination); and placebo plus peginterferon alfa-2b plus ribavirin (control).

Patients for the phase IIb study will be selected based on having genotype 1 chronic HCV and having failed to respond to pegylated alpha interferon plus ribavirin therapy (non-responders). Patients who respond to therapy during the phase IIb trial will have the option to continue on treatment for up to 48 weeks. The study will measure viral load at various time points, as well as a number of safety parameters.

"This is an important step in the development of celgosivir", stated Dr Jim DeMesa, president and CEO of Migenix. "Our recent agreement with Schering- Plough, the strong preclinical synergy of celgosivir with interferon-alpha plus ribavirin, and the participation of many of the same investigators from our phase IIa trial - combined with this regulatory approval - give us great encouragement for success in this phase IIb trial."

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August 10, 2005

Tarvacin Studied for HCV

This is an unusual post for us. First we have the official press release on a new approach to HCV and then the comments from an interested observer. We think you will find this information to be of great interest.

Tarvacin(TM) starts with Phase I study against Hepatitis C Virus
Aug 8, 2005, 17:40

"Tarvacin(TM) is truly a novel approach to treating HCV and we are eager to offer patients the opportunity to participate in this trial."

By Peregrine Pharmaceuticals, Inc., Enrollment Open for Patients Chronically Infected With Hepatitis C Virus (HCV)

Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM), announced today the initiation of a phase I anti-viral study of Tarvacin(TM), the Company's first Anti-Phospholipid Therapy candidate. The phase I study is an open-label, dose-escalation study in up to 32 adult patients with chronic hepatitis C virus (HCV) infection who either no longer respond to or failed standard therapy with pegylated interferon and ribavirin combination therapy.

The objectives of the trial are to evaluate safety, pharmacokinetics and viral load following a single intravenous infusion. The study is being conducted at Bach and Godofsky Infectious Diseases, the largest private infectious disease practice specializing in the treatment of viral hepatitis in the United States. Bach & Godofsky is located in Bradenton, FL.

"Tarvacin(TM) is truly a novel approach to treating HCV and we are eager to offer patients the opportunity to participate in this trial," stated Eliot W. Godofsky, M.D., Principal Investigator and clinical assistant professor of medicine at the University of South Florida in Tampa.

"This study is an important step for our Tarvacin(TM) antiviral program," said Joseph Shan, Peregrine's senior director of clinical and regulatory affairs. "Meanwhile, we are continuing our Tarvacin(TM) development efforts for other viral diseases."

CJ Gaddy Comments:

Anyone interested the fight against HEP-C should be aware of the phase1 study of TARVACIN initiated 8-8-05 at Bach & Godofsky Infectious Diseases in Bradenton, FL., with Dr. Eliot W. Godofsky as principle investigator.
[news: http://tinyurl.com/cltum ]

Trial Title: “This phase I study is an open-label, dose-escalation study in up to 32 adult patients with chronic Hepatitis C virus (HCV) infection who either no longer respond to or failed standard therapy with pegylated interferon and ribavirin combination therapy.”

Go to the Tarvacin website to learn about Tarvacin and the HEP-C Trial:

http://www.tarvacin.com – click “Patient Resources” to bring up the TARVACIN overview page. Then click TARVACIN-FOR-VIRUSES how Tarvacin anti-viral works. Note the TARVACIN-FOR-CANCER button - Tarvacin treats both cancer and viruses! Phase I Trial info. (for both Cancer and HEP-C) are further down the left column, including eligibility req’s and Peregrine contact info:
Ph: 800-694-5334, email: clinicalaffairs@peregrineinc.com

Also, ClinicalTrials.gov has more info. on this Tarvacin HEP-C Trial:
http://clinicaltrials.gov/ct/show/NCT00128271
Site Contact: Bach & Godofsky, Bradenton Ph: 941-746-2711 x39

The primary goal of this Phase1 trial is, of course, to prove safety, but read carefully how they worded the trial objectives: “To determine safety and tolerability, characterize blood pharmacokinetics and viral kinetics, define the maximum tolerated dose (MTD) and/or maximum effective dose (MED)”. It SEEMS (my opinion only) the scientists are expecting to see efficacy even at initial low phase1 dosages. To see why they may think so, read about Tarvacin anti-viral animal results presented at BIO2005 6-22-05: http://tinyurl.com/dqf9t

Tarvacin Background:

TARVACIN is a monoclonal targeting antibody drug developed by Dr. Philip Thorpe of UT-SW/Dallas, whose research is funded by Peregrine Pharmaceuticals, the NIH/NIAID (Infectious Diseases), the USAMRIID (BioDefense), and the Susan G. Komen Breast Cancer Foundation. Scientifically, Tarvacin is the chimeric form (mostly human, part mouse) of the Anti-Phosphatidylserine (Anti-PS) antibody “3G4”, the lead product under Thorpe’s Anti-Phospholipid Therapy (APT) platform.

Tarvacin is effective against both CANCER and VIRUSES. A great simple explanation of Tarvacin’s MOA was written by Michael Brush 7-28-05:

“The cells in our bodies are contained by membrane made up of phospholipids which normally know how to position themselves in the right way. But in cancerous cells these phospholipids get confused. Many of them end up on the outside of the cell. That turns them into great targets – if you want to shoot a missile at a cancerous cell inside the body to kill it. A similar thing happens in cells infected by many common viruses. These viruses replicate by entering cells, reproducing in the nucleus, and then exiting the cell. On the way out, however, they get enveloped by parts of the membrane from the host cell. Again, this confuses phospholipids in the membrane of the virus cell, and the phospholipids wind up on the outside of cells. That creates another great target if you want to launch an attack. The key compound that knows how to zero in on target cells is called Tarvacin.”
[M.Brush article: http://tinyurl.com/9z7yf ]

You read right: Tarvacin’s universal nature makes it able to attack and destroy ALL SOLID CANCER TYPES, as well as ALL ENVELOPED VIRUSES (ex: Hep/B+C, Influenza, Pneumonia, SARS, HIV/AIDS, Ebola, Marburg, Lassa…).

In addition to the HEP-C trial that is the subject of this email, a Tarvacin phase1 trial to treat ALL-SOLID-CANCERS was initiated 6-10-05 at The Arizona Cancer Center: http://ir.peregrineinc.com/phoenix.zhtml?c=74236&p=irol-newsArticle&ID=719219

The U.S. Gov’t is highly interested in the ANTI-VIRAL side: On 4-4-05, following an 8-2003 $1.68mm grant to Thorpe to test 3G4 against Lassa Fever, the NIAID announced their testing labs will screen Peregrine's APT agents, including Tarvacin, for activity against a “broad spectrum of enveloped viral pathogens” of health and bioterrorism concern, including Herpes viruses, respiratory viruses, pox viruses, HEP B/C, Papillomavirus and viruses of biodefense concern including Pichinde, Yellow Fever, West Nile and Dengue. [NIAID: http://tinyurl.com/5ntcm & http://tinyurl.com/8k9qj ] On 7-21-05, the U.S. Army's USAMRIID announced they will test Tarvacin against Ebola & Marburg Viruses, under the direction of Dr. Thomas W. Geisbert, Chief, Dept. of Viral Pathology and Ultrastructure at USAMRIID, Fort Detrick, MD." [Army: http://tinyurl.com/8ny2g ]

Most critically, animal tests suggest Tarvacin is very safe: extensive primate tests have shown no signs of toxicity until dosage is raised to 10x predicted therapeutic dosage. We all know safe Primate testing is a long way from safe Human testing, but Thorpe’s comment here is encouraging, “The phospholipids that 3G4 recognize have the same structure and cellular distribution in different mammalian species, simplifying the transition from experimental animals into humans.” [ http://tinyurl.com/5ntcm ] Well, these two Phase1’s are about to tell us about safety.

On the ANTI-VIRAL side as well, another important statement about Drug Resistance from Michael Brush’s article, “Most of the excitement right now surrounds potential treatments of the so-called “enveloped” viruses – the ones that envelope themselves with bits the host cell membrane as they exit the host cell. The “enveloped” viruses read like a top10 list of diseases you’re most likely to get, and really don’t want. They range from influenza and Hepatitis B+C, to herpes, West Nile, Dengue, HIV, SARS, Avian flu and many of the potential bio-terror “hemorrhagic” viruses, like Ebola. A great thing about Peregrine’s approach is that viruses can’t mutate to fight off the Tarvacin attack. That’s because Tarvacin keys in on anomalies in the cell membrane – the confused phospholipids -- that viruses don’t know how to fix. “Since it is not made by the virus, it is not mutable by the virus,” says Peregrine’s CEO Steven King. “It is not something the virus can change, to get away from therapy.”

Virologist Dr. Stephen Smith (Chief of Infectious Diseases, St. Michael's Medical Center), a Peregrine advisor, said 2-8-05, “this approach represents an entirely new way of combating infectious diseases. Instead of targeting viral proteins, Peregrine's product attacks altered, endogenous phospholipids. Therefore, drug resistance cannot develop." [ Dr.Smith: http://tinyurl.com/9qwen ]

In closing, here are a few links that you might find interesting to learn more about Dr. Thorpe’s APTs, beyond the current HEP-C trial:

www.peregrineinc.com – Peregrine Pharmaceuticals website
http://ir.peregrineinc.com/phoenix.zhtml?c=74236&p=irol-news – Press Releases
http://tinyurl.com/b9hdq - my amateur compilation of Articles, Quotes, etc.
http://tinyurl.com/6yz4x - investment board, but iBox News section up top is accurate

Compiled by:

cjgaddy@earthlink.net

Note: I am a retired computer guy, a follower for years of Phil Thorpe’s discoveries (not just APTs!), as well as an investor in Peregrine. I do these compilations of facts and opinion strictly on my own, and am in no way endorsed or supported by Peregrine or any of Peregrine’s scientists. Everything I put together is factual or the documented opinion of experts, publicly available, and backed by web links to reputable sources. If I make an error, or fail to provide a link, please email me and I’ll correct it immediately.

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August 07, 2005

Another HCV Treatment Advance

Here is another report of progress being made with a unique approach to treatment of the Hepatitis c virus. With so many companies working on a treatment, the odds are on our side that one will be proven and approved in the next 5 years or so.

Genelabs Drug Discovery Team Advances Compounds Against the Hepatitis C Virus in Preclinical Development

REDWOOD CITY, Calif., Aug. 4 /PRNewswire-FirstCall/ -- Genelabs Technologies, Inc. (Nasdaq: GNLB) today announced that a non-nucleoside compound from its internal Hepatitis C virus (HCV) drug discovery program has advanced into preclinical development. The compound, designated GL60667, is the second Genelabs non-nucleoside compound to advance into preclinical development.

Genelabs also announced that the company has further advanced GL59728, its first non-nucleoside preclinical development candidate. Genelabs plans to initiate Good Laboratory Practices (GLP) preclinical studies on GL59728 which, if successful, would enable the company to file an Investigational New Drug Application (IND) for the compound. Genelabs retains all commercial rights to its non-nucleoside compounds. Genelabs based its decision to advance compound GL60667 on rigorous pre- determined standards, including various measures of potency, metabolism, pharmacokinetics and toxicity. Genelabs believes that compounds meeting these criteria should hold a competitive advantage over other non-nucleoside HCV inhibitors described in the scientific literature. GL60667 has demonstrated the following properties in in vitro assays:

-- potency of approximately 40 nanomolar against an HCV replicon. -- potency of approximately 20 nanomolar for inhibition of the HCV polymerase. -- potency against the major genotypes of HCV, including genotype 1, the most common genotype in the United States and western Europe.

The concentration of GL60667 that is effective in reducing HCV replication is more than 100 times lower than the concentration that causes toxicity to various human cell lines, as demonstrated in a battery of tests conducted by Genelabs. Genelabs also has profiled the metabolic and pharmacokinetic properties of GL60667 in several different animal species. Extrapolating from this data, Genelabs believes the compound should be suitable for once-a-day dosing.

Separately, Genelabs advanced its first non-nucleoside preclinical candidate, GL59728, into IND-enabling studies based on favorable results from 1-day and 7-day toxicology studies in two animal species. Selection of a vendor for process development and large-scale synthesis is underway.

"The preclinical results generated to date from our hepatitis C virus drug discovery efforts demonstrate the depth and breadth of our research programs in this important and growing therapeutic area," stated James A.D. Smith, president and chief executive officer. "We know of only a handful of HCV drug discovery programs targeting the polymerase that have moved into preclinical development, and we believe ours has produced the most exciting results thus far. I am very pleased with the progress we have demonstrated towards our goal of developing best-in-class compounds targeting the hepatitis C virus."

In addition to its non-nucleoside HCV drug discovery program, Genelabs also has an HCV drug discovery program using nucleoside compounds under a September 2004 research collaboration and license agreement with Gilead Sciences, Inc.

Apart from the nucleoside and non-nucleoside HCV polymerase drug discovery programs, in 2004 Genelabs initiated a third HCV drug discovery program focusing on another target essential for HCV replication. This target is encoded by the region of the HCV genome known as NS5a. Genelabs believes compounds targeted at NS5a could lead to drugs that inhibit HCV by a novel mechanism.

As such, these compounds may be particularly attractive for combination treatment regimens in HCV. In preliminary studies, Genelabs' small molecule compounds in this program can inhibit the HCV replicon with minimal toxicity to human cell lines. The company has generated initial lead compounds which are in the process of optimization.

About Hepatitis C

The Hepatitis C virus is an infectious and potentially fatal virus that can be contracted through blood and bodily fluid contact. The virus attacks the liver and can cause liver inflammation, liver scarring, liver failure and liver cancer. In most cases, the body is not able to fight off the infection and the infected individual becomes a chronic carrier of HCV. According to the World Health Organization, as many as 170 million people worldwide have chronic HCV infection.

The United States Centers for Disease Control and Prevention estimates that approximately 2.7 million people in the United States are chronically infected with HCV and that each year there are approximately 25,000 new cases of HCV infection and approximately 8,000 to 10,000 deaths from hepatitis C complications. Liver failure resulting from chronic HCV infection is now recognized as the leading cause of liver transplantation in the United States.

The current standard of care for treatment of HCV is a combination of pegylated interferon alpha and the nucleoside analogue ribavirin, typically given over a number of months, withinterferon injected once weekly and ribavirin given orally once daily. This treatment regimen is effective only in approximately 50% of patients infected with HCV genotype 1, the genotype most prevalent in the United States. The interferon/ribavirin treatment has significant toxicities, most importantly severe anemia and psychiatric effects. There are no other drugs or biologics approved by the FDA for treatment of HCV. As a consequence, the pool of patients continues to grow.

About Genelabs

Genelabs Technologies, Inc. is a biopharmaceutical company focused on the discovery and development of pharmaceutical products to improve human health. We have built drug discovery and clinical development capabilities that can support various research and development projects. Genelabs is currently concentrating its capabilities on developing a late-stage product for lupus, discovering novel compounds that selectively inhibit replication of the hepatitis C virus and advancing preclinical development of compounds from this hepatitis C virus drug discovery program. We believe that these high-risk, potentially high reward programs focus our research and development expertise in areas where we have the opportunity to generate either first-in-class or best-in-class products that will address diseases for which current therapies are inadequate.

Posted by Ralph at 07:37 AM --- Printer-friendly version | Comments (3)

August 03, 2005

HCV Fighters

This is an article from Forbes. Again, the business side of this disease can provide quite a bit of information for us patients. The fact that Credit Suisse First Boston likes VX-950 is certainly a good sign.

Stock Focus
Hepatitis Fighters
Peter Kang, 08.03.05, 8:30 AM ET

NEW YORK - In the stock market, the biotechnology sector is one of the more speculative places to put your money. Standard & Poor's reports that of the 340 biotech companies traded on U.S. exchanges, only 14 are consistently profitable.

But if you want to take a biotech gamble, try smaller companies focused on developing antiviral treatments, particularly cures for liver diseases. Why? Market opportunity.

One such family of ailments, hepatitis B (HBV) and hepatitis C (HCV), infects more than 5 million Americans, according to the Centers for Disease Control and Prevention. Hepatitis is the leading cause of chronic liver disease, the tenth major cause of death in the U.S. Some health experts predict that the death rate from the more deadly hepatitis C virus may surpass that of HIV/AIDS by 2015.

Idenix Pharmaceuticals (nasdaq: IDIX - news - people ) has promising drug candidates for both HBV and HCV. The company also boasts the support of Swiss drug giant Novartis (nyse: NVS - news - people ), which is co-developing a compound called Telbivudine for HBV.

According to Mark Schoenebaum, a biotech analyst with Bear Stearns, shares of Idenix, which carved out a new all-time high yesterday, could climb even higher if Novartis opts to take a stake in NM-283, an HCV treatment developed by Idenix.

"We believe NM-283 Phase IIb data in hepatitis C will be the most important event for Idenix this year," Schoenebaum said in a June 22 report. He expects positive data for NM-283 to be released by Idenix in September. He also thinks Idenix, which recently announced positive Phase III clinical trial data for Telbivudine, could see an upside spark in shares on a potential Novartis opt-in for NM-283.

While Idenix shows a lot of promise, security analysts reporting to Thomson First Call don't expect the company to deliver profits until 2007.

Vertex Pharmaceuticals (nasdaq: VRTX - news - people ), another company for which profits are still elusive, has a potential blockbuster drug in its HCV drug VX-950, currently in early-stage development. Vertex shares rose 20% on May 10 after the company's Phase I results showed that VX-950 was well tolerated by patients and demonstrated "potent antiviral activity," according to a Vertex release.

In a June 2 research report, Credit Suisse First Boston analyst Mark Augustine wrote that VX-950 "is the most exciting small-molecule HCV antiviral drug in the clinic," and estimates peak annual sales of more than $1 billion. Augustine said a recent alliance forged by Novartis and Anadys Pharmaceuticals (nasdaq: ANDS - news - people ) bodes well for Vertex. The deal, potentially worth $570 million (with an upfront payment of $20 million and milestone payments of up to $550 million), indicates a willingness on big pharma's part to invest in companies with early-stage hepatitis drugs, according to Augustine.

Investors might want to look at Valeant Pharmaceuticals (nyse: VRX - news - people ) (formerly known as ICN Pharmaceuticals), whose stock price has dropped 26% from a December high. In addition to tackling hepatitis, Valeant sells drugs for treating neurological and dermatological disorders and other infectious diseases. Its shares sell for 46 times their consensus 2006 forecast.

Six Hepatitis Fighters

Anadys Pharmaceuticals (nasdaq: ANDS )

Idenix Pharmaceuticals (nasdaq: IDIX)

Rigel Pharmaceuticals (nasdaq: RIGL)

Valeant Pharmaceuticals International (nyse: VRX)

Vertex Pharmaceuticals (nasdaq: VRTX )

ViroPharma (nasdaq: VPHM - news - people )

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June 24, 2005

Hepatitis C Hope

The following article is from Pharmaceutical Business Review. I don't know why, exactly, but I love it when these guys talk about Hepatitis c treatment as a business. Maybe it is because I figure their monetary interest fuels their desire to find better and better treatments for Hepatitis c.

What we can discern from reading between the lines in this industry report is that truly new and exciting treatments may still be 5 or six years off. While it is not tomorrow, it is also not decades away. I find that encouraging.

Hepatitis C: hope on the distant horizon

24 Jun 2005, 17:24 GMT - While progress in the hepatitis C virus market is expected to be slow until 2011, the launch of polymerase and protease inhibitors thereafter is expected to fuel rapid growth. The market is expected to exceed $4 billion by 2012 and this growth may even result in a new treatment paradigm.

Driven by a favorable epidemiology and high unmet medical need, the hepatitis C pipeline is both rich and varied. The chronic hepatitis C (CHC) treatment market is currently dominated by market leaders Roche and Schering-Plough, which market both components of the CHC standard of care - a combination of pegylated interferon (Peg-IFN) alfa and ribavirin (RBV).

Historical growth in the hepatitis C market has been high, with a compound annual growth rate (CAGR) of 28.5% experienced between 1999 and 2003. This was mainly fuelled by the launch of RBV in 1998 and the second-generation interferons, Peg-IFN alfa-2b and -2a in 2000 and 2002, respectively - both of which significantly improved the efficacy of therapy.

However, treatment outcomes following Peg-IFN plus RBV combination therapy are highly heterogeneous and depend on the viral genotype with which a patient is infected. Indeed, sustained viral response (SVR) rates in the 'easy-to-treat' genotypes 2 and 3 can be up to 88% of cases. In contrast, less than half of those who harbor hepatitis C virus (HCV) genotype 1 successfully respond to therapy. Significantly, genotype 1 accounts for between 70 to 75% of the patient pool in the West and, therefore, current therapy meets less than 50% of the CHC medical need.

This has led to the accumulation of patients that have failed first-line therapy with the current standard of care, known as non-responders, and patients who responded to therapy but subsequently relapsed. Moreover, as a result of the slow rate of HCV disease progression, the wave of patients seeking treatment is still gaining momentum and expected to peak from 2014 onwards.

Incremental improvements in short term

The combination of high patient potential and significant medical unmet need have attracted big pharma and small biotech alike, creating a pipeline consisting of 28 drugs in clinical development and a range of potential drug candidates at the preclinical stage. However only 14% of these molecules are currently in phase III, with none of these specifically targeting the HCV particle per se. Instead, they act by enhancing the host antiviral response and therefore, no major paradigm changes are expected to occur in HCV therapy for at least the next five years.

Research by Datamonitor found that among the three drugs that are closest to market, only Valeant's RBV follow-up drug viramidine is perceived as a key addition to HCV therapy. The drug has similar efficacy to its predecessor but differentiates itself based on its more favorable toxicity profile.

The highest hopes for effective future HCV therapy are being pegged on the small molecules able to specifically interfere with HCV replication, in particular the NS3 protease inhibitors. This new paradigm was first highlighted as a realistic goal by Boehringer Ingelheim (BI), whose protease inhibitor BILN 2061 demonstrated an unprecedented drop in viral load after only two days of therapy. However, the enthusiasm was largely dampened when BI was forced to suspend further development of the drug due to cardiac toxicity in animals.

With the most developed protease inhibitor - Vertex/Mitsubishi's VX-950 - still at least seven years from reaching the market, hopes are now centered on the polymerase inhibitors, most notably Idenix/Novartis's NS5B polymerase inhibitor valopicitabine (NM283). However clinical development has also led to general disappointment when early-stage trials showed only moderate reductions in viral load with NM283 monotherapy. This led to subsequent clinical trials being designed for combination therapy with Peg-IFN, with the end goal of potentially replacing RBV with NM283.

Is future therapy without an interferon backbone realistic?

Early results from the NM283 clinical trials raise the question about the future role of Peg-IFN in HCV therapy: will it remain the backbone for several years to come or eventually fade from use? Some people believe that future HCV therapy is more likely to consist of combination therapy, based on Peg-IFN plus one or more specific antivirals. Others take a more optimistic view nurtured by faith in that antivirals could be capable of curing HCV infection on their own.

Given the consequences of untreated HCV infection, which include liver cirrhosis, hepatocellular carcinoma, liver transplant and death, many physicians will require convincing data before replacing a proven therapeutic option with antiviral monotherapy. As such, Peg-IFN is expected to retain a relatively strong market presence, despite the plethora of drugs in the pipeline, resulting in a CAGR of 9.9% for the interferon class between 2004 and 2013.

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June 20, 2005

Once A Month Interferon

Albuferon is an interferon that can be taken once a month and has less side effects than other interferons. It is closer to approval than other drugs being developed and seems like a better option than existing therapy.

New Approach To Hepatitis C

June 20 (ABC7) — A new drug is offering hope for millions of Hepatitis C patients. As Dr. Dean Edell reports, this drug may help patients stay healthier with fewer side-effects.

Superstar Billy Graham took home the Worldwide Wrestling Federation title in 1977, but what happened in the ring brought him a challenge he never expected.

Superstar Billy Graham, retired professional wrestler: "We cut our foreheads to produce blood to make the match look more authentic."

Graham thinks that may be how he contracted Hepatitis C. The disease is most commonly spread through blood.

Vijayan Balan, M.D., hepatologist: "Hepatitis C is a virus that can infect the liver and cause cirrhosis if it is untreated."

Dr. Vijayan Balan is a liver specialist working on a new treatment.

Dr. Balan, M.D.: "I think there is significant hope in conquering this disease."

Right now, patients must take medication once a week that can induce days of flu-like symptoms. Now a new drug, Albuferon, is only taken once a month and causes fewer side-effects.

Dr. Balan, M.D.: "They get the drug more continuously for a longer period of time."

Albuferon is a combination of Interferon, which helps fight infection and Albumin, which allows the medication to stay in the body longer.

Dr. Balan: "You don't have the peaks and valleys with this new drug."

Studies show the drug is safe. Soon it will be tested in up to 1,000 people across the country.

Graham says a drug that's easier to handle would have had him back in the gym sooner and able to focus on the good times.

The first phase of the study showed Albuferon is safe and well tolerated by patients. Right now, more than 1000 people are taking the drug.

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May 17, 2005

Vertex Update

This is an update on the earlier story about VX-950. I've put it up here because it gives a bit of a different perspective.

I love the part where Boger says, "We believe it will take weeks or months to defeat the virus..." and then he contrasts it to the current full year of treatment.

Also, be sure to note that they are claiming this drug has none of the negative side effects of current therapy. Hooray!

Vertex says drug quickly treats hepatitis C
17 May 2005 20:20:21 GMT
Source: Reuters
(Adds details on virus returning in 5 patients, share price)
By Ransdell Pierson

NEW YORK, May 17 (Reuters) - Vertex Pharmaceuticals Inc. on Tuesday said half of hepatitis C patients taking a specific dose of its experimental drug in an early-stage trial tested negative for the virus 14 days after beginning treatment, a speed unmatched by any existing medicine.

The tiny U.S. biotechnology company said the patients received a 750-milligram dose of its medicine, called VX-950, every eight hours during the two-week Phase 1 trial.

Results of the 34-patient study, which was conducted among patients with the hardest-to-treat genotype 1 strain of the virus, were presented at the annual Digestive Disease Week scientific meeting being held in Chicago.

"The big surprise is that half of patients in 14 days in this drug group went below levels of virus detection," Vertex Chief Executive Officer Joshua Boger told Reuters.

By contrast, he said current two-drug treatments typically must be taken for three months before half of patients reach undetectable levels of the virus. They must then be taken another nine months to make sure the virus does not re-emerge.

"Our drug by itself appears to be dropping the virus to undetectable levels dramatically quicker than standard combination treatments," Boger said, and without the flu-like side effects or other problems seen with existing medicines.

Another patient in the Vertex-sponsored trial also tested negative for the virus after receiving a different dose of VX-950.
The virus returned to detectable levels in five patients a month after the Vertex trial concluded, but virus levels remained more than 90 percent below original levels in two of them, the company said.

Boger said he is hopeful longer treatment in larger future trials will prevent the virus from re-emerging after it is knocked down.
Consequently, he said several Phase 2 trials that could begin late this year will last one to three months, testing the drug by itself and with at least one interferon used in current combo treatments, sold by Schering-Plough Corp. and Roche Holding AG . .
"We believe it will take weeks or months to defeat the virus, and we'll conduct the studies to find out," said Boger, who noted that standard treatments last almost a full year.

Shares of Vertex closed up 22 cents, or 1.7 percent, at $13.20 on the Nasdaq.

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May 16, 2005

Schering vs. Roche

What I find most significant about this report is that genotype 1 patients got somewhere between a 48% and 54% success rate. No wonder other drug companies are scrambling for an alternative treatment. It shouldn't be too hard to beat a 50-50 chance.

I also wonder what the results would have been if both drug therapies had been given in a weight based dosing manner. Perhaps Roche would have been the big winner. This helps demonstrate why variables are so important to look at when reading about clinical studies.

Schering-Plough hepatitis drug beats Roche's -study

16 May 2005 20:10:38 GMT
Source: Reuters
(Adds Roche criticism of trial)
By Ransdell Pierson

NEW YORK, May 16 (Reuters) - Schering-Plough Corp.'s combination treatment for hepatitis C was more effective in eliminating the virus than Roche Holding AG's better-selling similar combination, according to a small study described on Monday.
The study, which analyzed how patients treated for hepatitis C at the Cleveland Clinic fared between 2001 and 2004, was described at the annual Digestive Disease Week meeting being held in Chicago this week.
Clinic officials said a higher percentage of patients who received Schering-Plough's therapy, especially those who were obese, eliminated the virus after treatment than those taking Roche's therapy.
Complete data from the informal retrospective study was available on 28 obese patients and 58 non-obese patients, all of whom were Caucasian and had been infected with the hardest-to-treat genotype 1 strain of the virus. None of the patients had previously been treated.
Dr. Nizar Zein, a professor of medicine at the Cleveland Clinic, said he reviewed the patient records because no formal head-to-head trials of the two leading therapies has been completed.

Schering-Plough is conducting such a trial, but its results will not be known until 2007.

Schering-Plough's combination consists of an injectable interferon called Peg-Intron that is given along with an antiviral pill called ribavirin for 48 weeks. Roche's combo includes an interferon called Pegasys, which is also paired with ribavirin for the same duration.
But the dosage of Schering-Plough's interferon is based on a patient's body weight, whereas all patients receive the same standard dose of Roche's interferon -- regardless of whether thin or obese.
Zein said the virus was eliminated in 53 percent of obese patients getting the weight-based Schering-Plough interferon, similar to the 48 percent of non-obese patients receiving it.

By contrast, 18 percent of obese patients receiving the fixed-dose Roche interferon cleared the virus from their bloodstreams. That was lower by a statistically significant magnitude than the 28 percent of non-obese patients taking the same therapy who eliminated the virus.
"It was extremely surprising that patient responses were so much better with (Peg-Intron's) weight-based dosing, especially in obese patients," Zein told Reuters. He said he received no funding from Schering-Plough but has received past funding from Roche.

Roche questioned the validity of the study, saying its findings were "totally inconsistent" with large formal clinical trials of Pegasys in which far higher percentages of hepatitis C patients emerged free of the virus.

"This misleading research, which is based on a small number of patients outside the controlled setting of a clinical trial, is not valid from a scientific perspective and does a disservice to hepatitis C patients and their physicians," said Juan Carlos Lopez-Talavera, Roche's medical director.

But Cleveland Clinic's Zein said drugs sometimes fare less well in "real-world" medical practice than in the carefully controlled settings of clinical trials.

An estimated 4 million Americans are believed to be infected with the hepatitis C virus. The damage it does to the liver, typically for 10 to 20 years before symptoms develop, is the biggest reason for undergoing liver transplants.

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May 13, 2005

Small Molecule Drugs Are Coming for HCV

The following appeared in "Pharmaceutical Business Review Online". While this is just a short blurb, it is quite informative. The prediction for two more effective drugs to be launced in the next six or seven years is very, very encouraging.

Hepatitis C: small molecules, big business

13 May 2005, 16:44 GMT - Although interferons and ribavirin currently dominate the hepatitis C treatments market and soon-to-be-launched products will predominantly be improvements to these types of drugs, small molecule antivirals are expected to gain a much greater footing in the long-term. Indeed, the launches of the first two hepatitis C virus (HCV)-specific small molecule antiviral drugs, expected in 2011 and 2012, are predicted to be instrumental in helping to grow the value of the HCV pharmaceutical market in the next decade.

Source: Datamonitor Researchwire

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May 12, 2005

Breakthrough HCV Therapy?

Vertex has been getting press on VX-950 for some time. Early tests were good which led to this Phase 1b study.

If all remains well with this drug it could be a major step forward in the process of treating Hepatitis c.

Stay tuned...

Experimental HCV Protease Inhibitor VX-950 Demonstrates Potent Anti-HCV Activity

Interim results of a Phase Ib study indicate that the experimental hepatitis C virus protease inhibitor VX-950 has potent anti-HCV activity and is well tolerated, according to an announcement from drug maker Vertex Pharmaceuticals. Within three days of treatment, the median reduction in HCV-RNA was greater than 3 log10 in all three VX-950 dose groups.

As an oral drug that shows potency and no serious adverse side effects, VX-950 has the potential to become a breakthrough therapy for chronic hepatitis C.

The study enrolled 34 patients with chronic genotype 1 HCV infection who were treated for 14 days with placebo or one of three dose regimens of VX-950. HCV genotype1 infection is the most difficult strain of HCV to treat and the most prevalent strain in the United States, Western Europe and Japan.

Every patient receiving VX-950 achieved greater than a 2 log10 reduction in HCV-RNA within the first three days of treatment, according to Vertex.

Complete results from the study will be presented on May 17 at DDW 2005 in Chicago. In accordance with the DDW embargo policy of the meeting, the specific data from the trial beyond what is described in today’s announcement from Vertex will not be disclosed until the DDW presentation.

Study Design

The Phase Ib clinical trial was a double-blind, randomized placebo-controlled study designed to evaluate the tolerability, pharmacokinetics and effect on viral kinetics of three doses of VX-950 -- 450 mg every 8 hours, 1250 mg every 12 hours, or 750 mg every 8 hours -- over a period of 14 days, with additional post-treatment follow-up.

A key goal of the study was to assess different dosing levels and frequencies for VX-950 to provide insight into dose selection for future monotherapy and combination therapy studies. Thirty-four patients with chronic genotype 1 hepatitis C virus infection were enrolled in the study; six patients received placebo and 28 patients received VX-950. The study was conducted at three centers in Europe. The trial included treatment-experienced and treatment-naive HCV-infected patients.

Results

Principal results of the Phase Ib clinical trial are as follows:

· VX-950 was well-tolerated across all three dose groups with no serious adverse events reported, and no treatment discontinuations.

· Treatment with VX-950 also resulted in significant reductions in plasma HCV-RNA. Within three days of treatment, the median reduction in HCV-RNA was greater than 3 log10 in all three VX-950 dose groups.

· In the dose group receiving 750 mg of VX-950 every 8 hours, there was a further reduction in viral levels between days 3 and 14 of treatment, with mean and median HCV-RNA reductions of greater than 4 log10 at day 14.

· Trough plasma concentrations of VX-950 were highest in the 750 mg every 8 hour dose group. In the 450 mg q8h and 1250 mg q12h dose groups, maximal effects were seen between days 3 and 7 of treatment.

· Subsequently, there was an increase of approximately 1 log10 in median HCV-RNA between days 7 and 14 evident in both groups.

Full analysis of the study, including a detailed pharmacokinetic and viral sequencing evaluation, is underway.

"Vertex is committed to developing innovative compounds for the treatment of chronic HCV infection. VX-950, one of the most advanced agents in a promising new class of direct antivirals, underscores that commitment," said Joshua Boger, Ph.D., Chairman and Chief Executive Officer of Vertex. "The demonstration of antiviral activity in this early clinical study is highly encouraging, and we look forward to sharing these data in greater detail at DDW next week."

Based on the results of the Phase Ib clinical study, the Company plans to explore the development of VX-950 as monotherapy and in combination with other HCV treatments. Vertex plans to consult with the US FDA and European regulatory authorities on the Company's development plans.

Vertex expects to file an investigational new drug (IND) application in the second half of 2005
to support Phase II clinical development of VX-950 in the United States. In collaboration with Vertex, Mitsubishi Pharma Corporation is developing VX-950 in Japan and certain Far East countries.

About Vertex

Sources

PR Newswire-FirstCall.
http://www.vrtx.com

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May 11, 2005

Phase 1 Trial of Tarvacin

Another experimental anti HCV drug in the pipeline! The more companies working on a solution, the greater the odds of a practical treatment for HCV genotype 1.

TUSTIN, Calif., May 5 /PRNewswire-FirstCall/ --

Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM) announced today that it has submitted an investigational new drug application (IND) to the U.S. Food and Drug Administration (FDA) to initiate a phase 1 clinical trial using Tarvacin(TM) to treat patients with chronic Hepatitis C virus infection.

The objectives of the phase 1 clinical protocol submitted in the IND are to evaluate safety, pharmacokinetics and viral load in patients chronically infected with Hepatitis C virus who have failed standard treatment.

There are estimated to be 2.7 million people in the U.S. and 170 million people worldwide with chronic Hepatitis C infection. "This IND filing is an important next step in expanding the potential of Tarvacin(TM)," said Steven King, president and CEO of Peregrine Pharmaceuticals. "We anticipate this anti-viral IND will be the first in a series of steps to explore the anti-viral potential of Tarvacin(TM)."

The new application is the second IND filing for Tarvacin(TM). The first IND allows enrollment of patients with any solid cancer and has been cleared by the FDA to begin patient enrollment. Peregrine Pharmaceuticals will work closely with the FDA to address any questions that may arise during review of the anti-viral IND submission.

Patient enrollment can begin once the clinical protocol has been accepted by the FDA and initiation of clinical sites has been completed. In the meantime, the company expects to treat patients in the phase I solid cancer clinical trial within the next few weeks.

Pre-clinical studies using Tarvacin(TM) for the treatment of viral diseases have yielded promising results in Lassa fever, influenza, and cytomegalovirus, which are included in a viral category called enveloped viruses. Based on Tarvacin's(TM) anti-viral mechanism, the drug has potential for the treatment of enveloped viruses including Hepatitis B and C, Human Immunodeficiency Virus (HIV), herpes, influenza including SARS and Avian flu and potential bioterrorism threats such as Marburg virus and Lassa fever.

About Anti-Phospholipid Therapy in the Treatment of Viral Diseases

Tarvacin(TM) is Peregrine's first product under its anti-phospholipid therapy technology platform. Anti-phospholipid therapy is a novel approach to treating cancer, viral infections and certain ocular diseases. It is based on the finding that aminophospholipids, which are basic components of the inner surface of the cellular membrane, become exposed on the outside of the cellular membrane in response to certain disease states such as virally infected cells and cancer. A large number of viruses significant to global health and security possess an "envelope" derived from their host cell membrane. Since viruses lack the means to maintain structural organization of the envelope, amino-phospholipids such as phosphatidylserine (PS) and phosphatidylethanolamine (PE) become exposed on the surface of these viruses, making them a potential therapeutic target. Peregrine Pharmaceuticals, together with its collaborators, has developed a series of monoclonal antibodies, including Tarvacin(TM), directed against aminophospholipids to take advantage of this property.

About Peregrine Pharmaceuticals

Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a broad portfolio of products under development directed towards the treatment of cancer, viruses and other diseases. The company is in the process of initiating patient enrollment in a Tarvacin(TM) clinical trial for the treatment of all solid cancers and in a Cotara(R) clinical trial for the treatment of brain cancer. In addition, the company has submitted an IND application to initiate a Tarvacin(TM) clinical trial for the treatment of Hepatitis C virus infection. Peregrine Pharmaceuticals is also developing Vascular Targeting Agents, Anti-Angiogenesis, and Vasopermeation Enhancement Agents (VEAs) for the treatment of cancer and other diseases. Peregrine Pharmaceuticals also has in-house expertise to develop and manufacture antibodies and recombinant proteins through its wholly-owned subsidiary, Avid Bioservices, Inc., (http://www.avidbio.com). Avid is engaged in providing contract manufacturing services and development of biologics for biopharmaceutical and biotechnology companies, including Peregrine. Copies of Peregrine Pharmaceuticals press releases, SEC filings, current price quotes and other valuable information for investors may be found at http://www.peregrineinc.com

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May 02, 2005

Fibrotest vs. Biopsy

While primarily about Hyperlipidemia, this article verifies that FibroTest has been validated in chronic Hepatitis c. So, why are doctors still using biopsies???

Screening for Fibrosis with Non-invasive Biomarkers (Fibrotest) in Hyperlipidemic Patients

Insulin resistance is a cause of liver disease that can lead to cirrhosis. Hyperlipidemic patients (HP) have multiple insulin resistance factors and frequent abnormal liver function tests. HP should be screened for significant liver fibrosis (bridging fibrosis: early F2, advanced F3, cirrhosis F4) but biopsy is inappropriate because of the high number of patients at risk.

The aim of the current study was to use FibroTest, validated in chronic hepatitis C, B, alcoholic and non-alcoholic steatosis, to identify HP with F2F3F4.

A consecutive cohort of HP, HCV-HBVneg, <50g alcohol/day, followed in a lipid center was analyzed. Fibrotest was retrospectively performed on frozen fasting sera (–80 C); a control group of blood donors was prospectively included. Fibrotest was performed blinded with security algorithms to identify high-risk of false negative/positive.

Results

Among 1,542 subjects, 40 (2.59%) were excluded using security algorithms, and 1,502 included: 50.3% female, median age 49yrs, 957 HP and 545 controls.

Among HP, 83.4% had cholesterol >=200mg/dl, 93.6% LDL-C >=100mg/dl, 17.5% triglycerides >=200mg/dl, 35.9% BMI >=27, 33% arterial hypertension, 31.8% insulinemia >=10mUI/ml and 13.7% glucose >=6mmol/L.

GGT or ALT were elevated (>=50 IU/L) in 215 HP (22.5%).

F2F3F4 were identified by Fibrotest in 25/957 (2.6%) HP, including 13 F2, 8 F3 and 4 F4 but in none (0%) of the 545 controls (P<0.0001).

Among 25 HP with fibrosis, 19 had normal ALT, 14 normal GGT, 12 normal ALT and GGT, 4 elevated ALT and GGT and 9 elevated ALT or GGT.

Factors associated (p<0.01) with fibrosis were higher age, BMI, triglycerides, uricemia, and insulinemia. In multivariate logistic regression, including alcohol consumption, insulinemia (P=0.003) and triglycerides (P=0.008) were the most significant risk factors.

In HP with triglycerides >=200 mg/dl prevalence of fibrosis was 8.3% and 6.6% with insulinemia >=10mUI/ml.

Conclusions

Based on these results, the authors conclude, “Screening strategies for liver fibrosis are feasible with biomarkers in high-risk groups such as HP.”

“Without such non-invasive strategies a liver biopsy would have been indicated in up to 22.5% of HP with elevated GGT or ALT and would have probably missed half of HP with fibrosis, who had normal GGT and ALT.”

Biopredictive Department, Metabolism Unit, Biochemistry Department, Transfusion Unit, and Hepato-Gastroenterology Department,GHPS, Paris, France.

05/02/05

Reference
M Munteanu and others. SCREENING FOR SIGNIFICANT FIBROSIS USING NON-INVASIVE BIOMARKERS (FIBROTEST) IN HYPERLIPIDEMIC PATIENTS (HP). Abstract 689. 40th EASL. April 13-17, 2005. Paris, France.

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April 22, 2005

Newly Identified Protein Inhibits HCV

This is another case where researchers are using what already works (to a limited degree) and trying to find a way to improve their success rate. Interferon lambda is a newly discovered (or isolated) interferon that seems to have some success against HCV in a petri dish.

The encouraging fact is that much research is being done in a variety of approaches to controlling and curing Hepatitis c.

Newly Identified Protein May Inhibit Hepatitis Virus

A newly identified family of proteins may inhibit replication of the Hepatitis B (HBV) and C (HCV) viruses say researchers from California. Their findings appear in the March 2005 issue of the Journal of Virology.

Hepatitis B (HBV) and C (HCV) are viruses that infect the liver, and in some cases can cause liver failure requiring a transplant for survival. The protein interferon, produced by animal cells when they are invaded by viruses, is released into the bloodstream or intercellular fluid to induce healthy cells to manufacture an enzyme that counters the infection. One class of interferons (alpha) is used to treat chronic infection with HBV and HCV. There is a vaccine available to prevent the spread of HBV but not HCV.

In the study, a new class of interferons, interferon lambda, was tested for its ability to inhibit HBV and HCV replication. Results showed 90% inhibition of HBV after twenty-four hours and 90-99% inhibition in HCV five days posttreatment.

“We have demonstrated here that replication of HBV and HCV is sensitive to the antiviral activities of interferon lambda,” say the researchers. “These results suggest the possibility that interferon lambda may be therapeutically useful in the treatment of chronic HBV or HCV infection.”

(M.D. Robek, B.S. Boyd, F.V. Chisari. 2005. Lambda interferon inhibits hepatitis B and C virus replication. Journal of Virology, 79. 6: 3851-3854.)

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April 17, 2005

Viramidine Causes Less Anemia

Yet another variation on a theme. This one causese much less anemia than Ribavirin but is not more effective.

Viramidine Demonstrates Anti-HCV Genotype 1 Activity That Compares Favorably to Ribavirin, But without Complications of Severe Anemia

Dose-limiting anemia can be a prominent adverse event of therapy with pegylated interferon and ribavirin. This dose-ranging study examined whether viramidine, a liver-targeting prodrug of ribavirin, may be a safer alternative when used in combination with pegylated interferon alfa-2a/ PEG-IFN (Pegasys).

Of 180 HCV therapy-naive patients enrolled in the study, 171 patients received full-dose viramidine (400 mg: n = 47; 600 mg: n = 43; 800 mg: n = 44) versus ribavirin 1000-1200 mg/d (n = 37) in combination with PEG-IFN 180 µg/wk SC.

Patients were predominantly male (64%), Caucasian (76%), and genotype 1 (72%), with a median HCV RNA of 6.5 log10 copies/mL. Analyses assessed the incidence of anemia (hemoglobin <10 g/dL) and HCV RNA levels (Bayer TMA assay; sensitivity to 5 IU/mL) among patients without dose reduction due to anemia to evaluate the intrinsic activity of viramidine versus ribavirin without the confounder of dose modification.

Results

Among patients with no dose modification due to anemia at end of treatment (EOT), no significant differences were noted between viramidine (400, 600, and 800 mg BID) versus ribavirin in the proportion of patients with undetectable HCV RNA levels (55%, 63%, 55%, and 62%, respectively).

Rates of anemia at EOT for the viramidine 400, 600, and 800 mg groups were 0%, 2%, and 11%, respectively, versus 27% for the ribavirin arm.

Based on evaluable patients at EOT experiencing a decline in hemoglobin of at least 25%, the rate in the ribavirin group (48%) was higher versus the rate in the viramidine groups (400 mg: 14%; 600 mg: 18%; 800 mg: 15%).

Other types of adverse events were similar between treatment arms.

Conclusions

In conclusion, the authors note that at EOT in this Phase 2 study, “Viramidine demonstrated antiviral activity comparable to that of ribavirin when used in combination with pegylated interferon alfa-2a among patients with no dose modification due to anemia.”

“Patients in the viramidine arms also showed a significantly lower incidence of anemia.”

“Data lock for the Phase 2 study will occur by December 1, 2004, and sustained virologic response rates and safety outcomes will be presented at the 2005 EASL meeting.”

California Pacific Medical Center, San Francisco CA, USA, University of Florida, Gainesville FL, USA, University of New Mexico, Albuquerque NM, USA, University of North Carolina, Chapel Hill NC, USA, Hospital of the University of Pennsylvania, Philadelphia PA, USA, Valeant Pharmaceuticals International, Costa Mesa CA, USA.

04/15/05

Reference
R G Gish and others. VIROLOGIC RESPONSE AND SAFETY OUTCOMES IN THERAPY-NAIVE PATIENTS TREATED FOR CHRONIC HEPATITIS C WITH VIRAMIDINE IN COMBINATION WITH PEGYLATED INTERFERON ALFA-2A. Abstract 91. 40th EASL. April 13-17, 2005. Paris, France.

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April 15, 2005

Another Interferon

Here is another form of interferon being tested. It seems to have less severe side effects than current therapy.

Be sure to note the part that states genotype 1 patients have a 50% chance of clearing the virus with current therapies. Generally, the pharma companies would like you to believe the success rate is higher than that. Some still wonder if it is really even that high (if you account for drop-out rates due to severe side effects).

It is good to know, however, that nearly every drug company is scrambling for a treatement of Hepatitis c because of the huge number of people infected worldwide.

Stay tuned...

Human Genome Sciences Reports Positive Results of Phase 2 Clinical Trial of Albuferon(TM) in Treatment-Naive Patients With Chronic Hepatitis C

Thursday April 14, 10:45 am ET

- Mean Reduction in HCV Viral Load of 3.2 log at Day 28 Observed in the Combined 900 mcg and 1200 mcg Dose Cohorts -

ROCKVILLE, Md., April 14 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. (Nasdaq: HGSI - News) today announced the results of a Phase 2 clinical trial of Albuferon(TM) (albumin-interferon alpha) in patients with chronic hepatitis C who are naive to interferon-alpha treatments. The results demonstrate that Albuferon is well tolerated, has a prolonged half-life and shows robust antiviral activity, with durable dose-dependent reductions in hepatitis C viral load.

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(Logo: http://www.newscom.com/cgi-bin/prnh/20010612/HGSLOGO )

The data were presented today in Paris at the 40th Annual Meeting of the European Association for the Study of the Liver (EASL) in an oral presentation entitled, "A Phase 2 Study to Assess Antiviral Response, Safety, and Pharmacokinetics of Albuferon in IFNalpha-Naive Subjects with Genotype 1 Chronic Hepatitis C."(1) The Phase 2 trial, which was conducted in Canada, was a randomized, open-label, multi-center, parallel-design, dose-ranging study to evaluate the safety, tolerability, pharmacology and optimal dosing of Albuferon.(2-3) A total of 56 patients were enrolled in the trial and randomized to 5 dose groups (200 mcg, 450 mcg, 670 mcg, 900 mcg and 1200 mcg).(4) Patients were given 2 doses of Albuferon monotherapy administered subcutaneously 14 days apart and were followed for safety and antiviral evaluations for a total of 6 weeks. The pharmacodynamic activity of Albuferon was evaluated based on hepatitis C (HCV) RNA viral load reductions over a 42- day period of exposure. One of the study objectives was to identify a range of active doses that Human Genome Sciences plans to evaluate in a larger 48- week study of Albuferon in combination with ribavirin in patients with HCV genotype 1 who are naive to interferon treatments.

The primary efficacy endpoint of the Phase 2 study was the rate of virologic response at Day 28, defined as at least a 2-log reduction in HCV viral load compared with baseline, or undetectable HCV viral load. The data presented show that Albuferon exhibited robust antiviral activity in genotype 1 HCV. A mean reduction in HCV viral load of 3.2 log at Day 28 was observed in the combined 900 mcg and 1200 mcg dose cohorts, with 69% of patients (18/26) in these cohorts showing a >2-log reduction in HCV viral load at Day 28. Undetectable viral load was observed at Day 42 (28 days after the second injection) in 23% of patients (6/26) in the combined 900 mcg and 1200 mcg dose cohorts. Robust dose-dependent viral kinetics were observed, with the majority of patients in the 900 mcg and 1200 mcg cohorts exhibiting a second- phase decline in viral load of >0.3 log per week, which has previously been shown to be predictive of sustained virologic response (SVR) in treatment with the pegylated interferons.(5) Reductions in viral load of equal to or greater than 2 log are reported in approximately 42% of genotype 1 HCV patients treated with pegylated interferon alpha products in combination with ribavirin.(6)

Consistent with clinical results to date(7-8), the results presented at EASL demonstrate that Albuferon remained in the blood substantially longer than is reported for recombinant interferon alpha and pegylated interferon alpha. Albuferon was detectable for up to 4 weeks following the second subcutaneous injection. The C-max (peak drug level) increases in a linear manner over the dose range evaluated (200-1200 mcg). Albuferon exhibited a median half-life of 148 hours, supporting dosing at intervals of 2-4 weeks. This compares to a reported mean (range) elimination half-life of 80 hours (50-140 hours) for Pegasys and 40 hours (22-60 hours) for PEG-Intron.(9-10)

The Phase 2 clinical trial results demonstrate that Albuferon was well tolerated with adverse events that were transient and mostly mild to moderate in severity. One serious adverse event was reported (acute colitis) and has subsequently resolved. There were no discontinuations due to reductions in hematologic cell counts. No subjects developed newly emergent antibodies to alpha interferon. One subject developed low-titer antibodies to human serum albumin. There was no apparent correlation between the emergence of antibodies and adverse events, antiviral response or pharmacokinetics.

Vincent Bain, M.D., Director of the Liver Unit and Professor of Gastroenterology, University of Alberta, said, "While therapies currently available for the treatment of chronic hepatitis C are effective, approximately half of genotype 1 patients fail to achieve sustained virologic response following treatment with regimens that include pegylated interferons. In addition, these therapies are frequently associated with side effects that require dose adjustments and may even require discontinuation of treatment. Most patients currently receive pegylated interferon once weekly, with daily doses of ribavirin. A significant need exists for more convenient treatment options with fewer side effects. The clinical results presented at the EASL meeting today show that Albuferon is well tolerated and exhibits a robust antiviral activity, with a pharmacokinetic profile that supports dosing at intervals of two to four weeks. These data are strongly supportive of further evaluation of Albuferon in combination with ribavirin in a larger study over a longer period of time in treatment-naive patients."

David C. Stump, M.D., Executive Vice President, Drug Development, said, "The results of the current Phase 2 trial will inform our identification of an optimal range of doses to evaluate in a larger 48-week combination study of Albuferon with ribavirin that we plan to conduct in treatment-naïve patients. These data, along with the preliminary results emerging from our ongoing Phase 2 combination study in treatment-experienced patients(3, 11), afford confidence in the ability to administer Albuferon actively and safely in combination with ribavirin to treatment-naive patients. We look forward to continuing our development of Albuferon as a potential treatment for chronic hepatitis C."

Hepatitis C is an inflammation of the liver caused by the hepatitis C virus. It is the most common chronic blood-borne infection in the developed world, and afflicts approximately four million people in the United States. The hepatitis C virus is transmitted primarily through significant or repeated exposures to infected blood. Intravenous drug use and sexual contact with infected persons account for the majority of new hepatitis C infections. When detectable levels of the hepatitis C virus in the blood persist for at least six months, a person is diagnosed as having chronic hepatitis C. The current standard of care for treating chronic hepatitis C is combination therapy consisting of pegylated interferon and ribavirin, an antiviral drug.(6, 9-10, 12-17)

Albuferon is a novel, long-acting form of interferon alpha. Recombinant interferon alpha is approved for the treatment of hepatitis C, hepatitis B and a broad range of cancers. Human Genome Sciences modified interferon alpha to improve its pharmacological properties by using the company's proprietary albumin fusion technology.

For more information about Albuferon, see http://www.hgsi.com/products/albuferon.html. Health professionals interested in more information about trials involving Human Genome Sciences products are encouraged to inquire via the Contact Us section of the Human Genome Sciences web site, http://www.hgsi.com/products/request.html, or by calling (301) 610-5790, extension 3550.

Human Genome Sciences is a company with the mission to treat and cure disease by bringing new gene-based protein and antibody drugs to patients.

HGS, Human Genome Sciences and Albuferon are trademarks of Human Genome Sciences, Inc.

This announcement contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. The forward-looking statements are based on Human Genome Sciences' current intent, belief and expectations. These statements are not guarantees of future performance and are subject to certain risks and uncertainties that are difficult to predict. Actual results may differ materially from these forward-looking statements because of the Company's unproven business model, its dependence on new technologies, the uncertainty and timing of clinical trials, the Company's ability to develop and commercialize products, its dependence on collaborators for services and revenue, its substantial indebtedness and lease obligations, its changing requirements and costs associated with planned facilities, intense competition, the uncertainty of patent and intellectual property protection, the Company's dependence on key management and key suppliers, the uncertainty of regulation of products, the impact of future alliances or transactions and other risks described in the Company's filings with the Securities and Exchange Commission. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today's date. Human Genome Sciences undertakes no obligation to update or revise the information contained in this announcement whether as a result of new information, future events or circumstances or otherwise.

Footnotes:
1. Bain V, et al. A Phase 2 study to assess antiviral response, safety,
and pharmacokinetics of Albuferon in IFN.-naïve subjects with genotype
1 chronic hepatitis C. 40th Annual Meeting of the European
Association for the Study of the Liver (EASL), Paris. April 14, 2005.
Oral presentation. (Abstract #18.)
2. (HGSI Press Release) Human Genome Sciences Initiates Phase 2 Clinical
Trial of Albuferon for the Treatment of Chronic Hepatitis C. May 26,
2004.
3. (HGSI Press Release) Human Genome Sciences Completes Enrollment in a
Phase 2 Clinical Trial of Albuferon in Treatment-Naïve Patients with
Chronic Hepatitis C. February 16, 2005.
4. It is important to note that the method of measurement for dose
determination in the Phase 2 study of Albuferon in treatment-naïve
patients is different from the method of measurement in the Phase 1/2
study of Albuferon. Accordingly, the 200 mcg dose in the current
study is equivalent to a 150 mcg dose in the Phase 1/2 study, the 450
mcg dose is equivalent to 340 mcg in the prior study, and the 1200 mcg
dose is equivalent to 900 mcg.
5. Neumann AU et al. The second phase HCV decline slope is the best
predictor of sustained viral response during treatment of chronic HCV
genotype 1 patients with peg-interferon-a-2b and ribavirin. 53rd
Annual Meeting of the American Association for the Study of Liver
Diseases, Boston. November 1-5, 2002. Abstract #778. Hepatology
2002: Vol 36 No 4, Pt 2 of 2.
6. Di Bisceglie AM, Rustgi VK, Thuluvath P, et al. Pharmacokinetics and
pharmacodynamics of pegylated interferon alfa-2a or alfa-2b with
ribavirin in treatment naïve patients with genotype 1 chronic
hepatitis C. Hepatology 2004;40,4;734a, abstract LB18.
7. Balan V, et al. Albuferon -- A novel therapeutic agent for hepatitis
C: results of a Phase 1/2 study in treatment-experienced subjects
with chronic hepatitis C. 55th Annual Meeting of the American
Association for the Study of Liver Diseases, Boston. November 2,
2004. Oral presentation (Abstract #265).
8. (HGSI Press Release) Human Genome Sciences Reports Positive Results of
Phase 1/2 Clinical Trial of Albuferon in Chronic Hepatitis C.
November 2, 2004.
9. PEGASYS® Physicians Desk Reference. (Last updated December 2003).
10. PEG-INTRON® Physicians Desk Reference. (Last updated September
2003).
11. (HGSI Press Release) Human Genome Sciences Initiates Phase 2 Clinical
Trial of Albuferon in Combination with Ribavirin in Treatment-
Experienced Hepatitis C Patients. November 30, 2004.
12. Strader DB, Wright T, Thomas DL, and Seeff, LB. AASLD practice
guideline: diagnosis, management, and treatment of hepatitis C.
Hepatology 2004 April; 39 (4): 1147-1171.
13. Hadziyannis SJ, Sette H, Morgan TR, et al. Peginterferon-.2a and
ribavirin combination therapy in chronic hepatitis C. Ann Intern Med
2004; 140:346-355.
14. Shiffman ML, Di Bisceglie AM, Lindsay KL, et al. Peginterferon alfa-
2a and ribavirin in patients with chronic hepatitis C who have failed
prior treatment. Gastroenterology 2004; 126:1015-1023.
15. Zeng N, Cohen CK, Schwartz P, Rai R. Treatment of HCV infected
patients, including non-responders to PEG-IFN alfa-2b/RBV, with PEG-
IFN alfa-2a/RBV: the Johns Hopkins experience. Digestive Disease
Week 2004 Internet Conference Report. Abstract #1233.
16. Zeuzem S. Heterogeneous virologic response rates to interferon-based
therapy in patients with chronic hepatitis C: who responds less well?
Ann Intern Med 2004; 140:370-381.
17. Management of Hepatitis C: 2002. National Institutes of Health
Consensus Development Conference.

Source: Human Genome Sciences, Inc.

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March 09, 2005

Big Pharma and HIV/Hepatitis Co-Infection

The following article is from Datamonitor. They report on industry trends and developments.

There are a couple of points that I find most interesting.

One is the estimate of HIV/HCV coinfection being 30% of HIV patients. This bodes well for having the powerful HIV community rally behind development of more effective HCV treatments.

The other is the fact that this industry "insider" source states that "this will also become and issue in the context of HCV antivirals once developmental HCV polymerase and protease inhibitors reach the market." Notice, they did not say "if", they essentially said "when".

So, there is more assurance that more and better treatments are on the horizon.

Big pharma set to move into HIV/hepatitis co-infection niche

8 Mar 2005, 19:02 GMT - While the European Consensus Conference gained a consensus agreement for the treatment of HIV/HCV coinfection, the definition of best practice for the management of HIV/HBV remains clouded by the lack of data. However, this is certain to change with BMS' entecavir trial in HIV/HBV co-infected patients. Datamonitor's Brigitte de Lima reports...

The first European Consensus Conference on the Treatment of Chronic Hepatitis B and C in HIV Co-infected patients, held in Paris in early March 2005, was the first of its kind. The initiative brought together leading hepatitis and HIV specialists who drew up recommendations concerning the management of HIV/hepatitis co-infections. The goals to be achieved with these are, firstly, consistent therapeutic approaches across Europe and, secondly, increased diagnosis and treatment rates.

The delay of the onset of AIDS due to highly active antiretroviral therapy (HAART) has led to a significant increase in the life expectancy of patients infected with the human immunodeficiency virus (HIV). As a consequence, the management of concurrent illnesses, such as hepatitis B (HBV) and C (HCV), has been gaining increasing importance. Clinical experience has shown that concurrent HIV infection accelerates the progression of the underlying liver disease.

Concomitant with the AIDS epidemic, the absolute number of HIV/HBV and HIV/HCV co-infected patients has been rising steadily as a result of the common routes of transmission for these viruses. HIV is predominantly transmitted by sexual contact and intravenous drug use (IVDU). While the former is also the major route of HBV transmission, the latter predominates for HCV. Thus, depending on how HIV is acquired, simultaneous infection with either hepatitis virus is common. It is currently estimated that 10-15% of HIV patients also harbor a chronic HBV (CHB) infection, while the proportion chronically infected with HCV (CHC) might be as high as 30%.

The implications for the pharmaceutical industry are varied. First of all, with the establishment of pan-European guidelines, HIV/HBV and HIV/HCV co-infections can be regarded as new indications in their own, requiring existing and developmental drugs to be clinically tested in the co-infected populations. Key issues associated with clinical trials in co-infected patients are the possibility of pharmacokinetic interactions between antivirals to treat viral hepatitis and components of the HAART regime, and, importantly, the risk of viral resistance to both HIV and the hepatitis virus. Although viral resistance is currently only an issue for HBV therapy, it is anticipated that this will also become an issue in the context of HCV antivirals once developmental HCV polymerase and protease inhibitors reach the market.

Some pharmaceutical companies have already taken a step forward in this respect by trialing their hepatitis drugs in co-infected patients. Roche, for example, has recently received approval for the use of Pegasys (pegylated interferon alfa-2a) and Copegus (ribavirin) for the treatment of HCV in HIV co-infected patients following favorable results for the APRICOT study. This clearly gives it the lead in this patient sub-group, as supporting clinical data represent a significant driver in drug prescription choices.

In the context of HBV co-infection, the pharmaceutical sector has been slower to respond. While this might be due to the lower rate of HBV compared to HCV co-infected patients, 10-15% versus 30%, it is more likely to be a consequence of the very nature of CHB disease progression. While current HCV therapy is finite and can lead to virus eradication, HBV eradication, commonly defined as seroconversion from the presence of HBV surface antigen (HBsAg) to HBsAg loss and anti-HBsAg seroconversion, is rarely achieved with approved treatment options. Thus, it is not currently known whether treatment should be maintained in light of an unsatisfactory virological response.

HIV/HBV co-infection is currently managed using antivirals with dual activity against both viruses, such as Epivir (3TC/lamivudine), approved for both viral diseases - albeit at different doses - and Viread (tenofovir disoproxil), approved for HIV only. However, 3TC is associated with high rates of resistance for both viruses, limiting its usage in this population. In contrast, tenofovir has a favorable resistance profile, but apart from small independent trials, the drug has not officially been tested for either HBV monoinfection or HIV/HBV co-infection.

HIV/HCV and HIV/HBV co-infections clearly represent major clinical unmet needs. The development of new European guidelines, and the growth potential of the field, has set the foundation for more investment from the private sector. Bristol-Myers Squibb has already identified this niche market, with its lead HBV compound entecavir currently undergoing a Phase II clinical trial for HIV/HBV co-infection. Datamonitor expects others to follow this example to achieve greater drug differentiation.

Posted by Ralph at 03:10 PM --- Printer-friendly version | Comments (2)

February 23, 2005

Scientists Replicate HCV in Lab

This marks still more progress in learning about the Hepatitis C virus. The more scientists can learn, the better the chances for finding a more effective treatment. Public release date: 22-Feb-2005

Contact: Marcia Vital
vitalm@mail.nih.gov
301-496-3583
NIH/National Institute of Diabetes and Digestive and Kidney Diseases

Scientists replicate hepatitis C virus in laboratory

New in vitro model system will allow study of therapeutics and virus life cycle
For the first time, scientists have replicated hepatitis C virus (HCV) in the laboratory. The ability to replicate HCV in cell culture will allow researchers to better study the life cycle and biology of this virus and to test potential antiviral compounds, which may lead to new therapies for the liver disease that results from infection with HCV.

Scientists at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), one of the National Institutes of Health (NIH), conducted the study, which appears in the Feb. 15, 2005 issue of Proceedings of the National Academy of Sciences (PNAS).

"Until recently, research on this infectious disease has suffered from the lack of a robust in vitro model system," says T. Jake Liang, M.D., Chief of the Liver Diseases Branch of the NIDDK and co-author of the study. "Our model system produced viral particles that have all the properties of the whole virus. This evidence together with an analysis of the replicated viral RNA supports a conclusion of viral replication and production."

The NIDDK group used a strain of HCV that would have applications to the greatest number of people – genotype 1, the major type of HCV of human infections worldwide and the type most resistant to current therapies. They constructed an HCV replica using a DNA copy of the original HCV single-strand RNA genome. They placed the DNA copy between two ribozymes, RNA molecules that have enzymatic function and can cleave RNA sequence at specific locations.

These two ribozymes were designed to generate the correct ends of the HCV genome and to act as start and stop buttons to gene activity. The construct was "naked," meaning that it contained only nucleic acids, the genetic material of the virus, and did not have the HCV viral envelope, a protective shell of lipids and proteins that surrounds the viral RNA in fully-formed HCV. The naked HCV construct was then placed into human liver cells in a cell culture medium.

The NIDDK scientists found evidence of HCV proteins and HCV RNA within the human liver cells in the culture. Electron microscopy showed evidence of high levels of viral particles resembling fully-formed HCV outside of the human liver cells in the culture medium. The researchers believe that the HCV construct contained within the human liver cells behaved like a true HCV infection by producing fully formed copies of the virus and releasing them from the host cell into the culture medium.

Further testing is needed before the researchers can determine if the viral particles produced in this system are in fact infectious. Also, this system only represents the tail end of the viral life cycle – viral replication, assembly and release from host cells. Another HCV model system is needed to show the beginning stages of the viral life cycle – viral entry into host cells and viral activity in the host cell before replication.

"With this cell-based system, we can screen compounds with a cell-based assay to look for inhibitors of virus replication," says Liang. "We can also apply this technique to develop model systems for other similar viruses."

HCV is a small, enveloped, single-stranded RNA virus in the family Flaviviridae. HCV is a major cause of liver disease in the United States and the world. One in a series of hepatitis viruses, HCV accounts for about 15 percent of acute hepatitis cases, 60 to 70 percent of chronic hepatitis cases, and up to 50 percent of cases of cirrhosis, end-stage liver disease, and liver cancer. Almost 4 million Americans, or 1.8 percent of the U.S. population, have antibodies to HCV indicating ongoing or previous infection with the virus. Approximately 10,000 to 12,000 deaths each year in the United States are due to HCV.

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Heller, Theo; Jonathan Auerbach; Tarice Williams; Tzivia Rachel Moreen; Allison Jazwinski; Brian Cruz; Neha Jeurkar; Ronda Sapp; Guangxiang Luo; and T. Jake Liang. "An in vitro model of hepatitis C virion production." Proceedings of the National Academy of Sciences, Vol. 102, No. 7, pp. 2579-2583.

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February 11, 2005

HCV Genotype 1 High Dose Therapy Achieves 90% Cure Rate

The following article from HivandHepatitis.com is quite encouraging for genotype 1 patients who believe they must eradicate the virus at any cost. The article is reporting on a study report appearing in the latest issue of the medical journal, Hepatology.

Apparently, two years of high dose, severe side effect, combination therapy actually "cures" the disease in these patients. These are the best results ever reported for genotype 1.

It is especially impressive in light of the fact that the rate for current combination therapy (at lower doses) is just 40% for genotype 1.

Dr. Baker is clearly excited at the prospect of this high a postive response, but is clear in pointing out that it appears to come at a very high cost (considering the severe side effects).

Nine of 10 Chronic Hepatitis C Patients Achieve a Cure 24 Weeks Post-treatment with High Dose Ribavirin Plus Standard Dose Peginterferon Alfa-2a (Pegasys)

By Ronald Baker, PhD

Ninety percent of genotype 1 patients with a high viral load enrolled in a pilot study in Sweden achieved undetectable HCV RNA 24 weeks post-treatment with a regimen of high dose ribavirin plus standard dose peginterferon alfa-2a (Pegasys). By standard definitions, this means they were cured. Results of the small pilot study appear in the current issue of Hepatology (February 2005).

Following are selected highlights of the study and the 72-week findings:

7 men, 3 women, with mean age of 51 participated (no African Americans, no cirrhotics);

All 10 participants were genotype 1, high viral load;

Patients coinfected with HIV or other diseases were excluded;

After dose adjustments, mean daily ribavirin dose was 2,540 mg/day (1,600-4,000) at week 2 (the recommended ribavirin dose is rarely above 1,200 mg/day);

Pegasys (peginterferon alfa-2a) dosing was standard: 180 microgram weekly;

Side effects were severe, particularly anemia and hemolysis; all patients required erythropoietin, and two patients required 2 separate blood transfusions;

Treatment duration was 48 weeks;

At the 24-week post-treatment follow-up, 9 of 10 patients had undetectable HCV RNA.

Background

Ribavirin is an antiviral drug that is approved in the US and Europe for use in combination with interferon alfa for the treatment of chronic hepatitis C. The current standard of care in both the US and Europe is combination treatment with peginterferon alfa-2a (Pegasys) or 2b (Peg-Intron) plus ribavirin.

Although the mechanism of action of ribavirn with interferon is not yet completely understood, it is believed to act in synergy with interferon to contribute to significantly increasing (perhaps doubling) the sustained viral response (SVR) rate by preventing virological relapse.

While the effectiveness of antiviral therapy for chronic hepatitis C has improved, individuals with HCV genotype 1, especially those with a high viral load, still do not generally experience an SVR. The SVR rate for these individuals using the current standard of care (peginterferon alfa plus ribavirin) is about 40%.

Ribavirin Dosing

One of the most controversial issues in the management of chronic hepatitis C is the question of what is the optimal dose of ribavirin and whether higher doses of ribavirin produce more effective results than standard doses?

The current recommendation for HCV genotype 1 patients is combination treatment with once weekly peginterferon alfa plus two daily doses of ribavirin for 48 weeks. The current recommended daily dose of ribavirn depends on which brand of interferon alfa is used. In the US, in combination with Pegasys, the FDA-approved dose for ribavirin is 1,000 or 2,000 mg daily, when total body weight is less than 75 kilograms or more than 75 kilograms, respectively; when used with Peg-Intron, the FDA-approved daily dose for ribavirin is a fixed dose of 800 mg. To confuse things even further, the approved daily ribavirin dose in Europe is weight-based, with 800 mg recommended for individuals weighing less than 65 kilograms, 1000 mg for individuals weighing 65-85 kilograms, and 1200 mg for those weighing more than 85 kilograms.

The Swedish Pilot Study

In the current pilot study, the objective was to evaluate the standard dose of peginterferon alfa-2a plus a daily dose of ribavirin that was individualized and calculated from a pharmacokinetic formula based mainly on renal function. In order to reach the targeted concentration of ribavirin in the blood serum, the study participants needed a mean ribavirin dose of 2,540 mg/day (range (1,600-4,000 mg/day). This equals more than double the currently recommended daily ribavirin dose.

Inclusion/Exclusion Criteria

The inclusion criteria for the pilot study were: age >18 years, elevated alanine aminotransferase, positive anti-HCV antibody test, detectable serum HCV RNA, and a liver biopsy consistent with chronic HCV but without cirrhosis.

Patients with other forms of liver disease, active hepatitis A or hepatitis B infection, hepatocellular carcinoma, human immunodeficiency virus infection, anemia, a previous diagnosis of severe depression or other psychiatric disease, significant cardiac disease, renal disease, seizure disorders, severe retinopathy, or pregnancy were excluded from the study.

Adverse Effects

The main side effect was anemia, which was controlled with erythropoietin. Two patients required blood transfusions. However, only minor treatment interruptions occurred among the ten patients who were treated with doses of ribavirin substantially exceeding standard doses. One patient was withdrawn at week 24 because of a lack of viral response, and one patient at week 39 because of side effects, primarily interferon associated.

Conclusions

At follow-up (24 weeks post treatment), nine of ten patients had undetectable HCV RNA. The primary goal of this small pilot study was to determine feasibility and safety of the treatment, and not virological outcome. However, in this difficult-to-treat patient population with genotype 1 and a high viral load, nine of ten patients were cured by standard definitions, which seems to be a better response than that found in studies using standard ribavirin doses.

The authors conclude, “A high dose of ribavirin according to an individualized schedule is feasible but associated with more frequent and serious side effects such as anemia. The viral response merits further evaluation.”

Although the promising results of this small pilot study were striking, and seem to open up a new direction in experimentation with ribavirin dosing and its relationship to improved SVR rates, it’s hard to ignore the potentially deleterious safety issues that might be encountered by many patients using such high ribavirin doses.

As well, cost issues must be considered, not just for the peginterferon and for the high ribavirin dosing, but also for the erythropoietin and possibly blood transfusions. Still, a 90% SVR for genotype 1 patients with high viral loads! It’s a thrilling thought to contemplate!

02/11/05

Departments of Infectious Diseases, Karolinska University Hospital Huddinge, Karolinska Institute, Stockholm, Sweden; Clinical Pharmacology, Karolinska University Hospital Huddinge, Karolinska Institute, Stockholm, Sweden; Renal Medicine, Karolinska University Hospital Huddinge, Karolinska Institute, Stockholm, Sweden.

Reference

K Lindahl, L Stahle, A Bruchfeld and R Schvarcz. High-dose ribavirin in combination with standard dose peginterferon for treatment of patients with chronic hepatitis C. Hepatology 41(2): 275-279. February 2005.

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January 24, 2005

Magic Bullet For Hepatitis C?

The following article from the Forbes magazine website is very informative.

The fact that Vertex is so far along with their protease inhibtor is very exciting. As is the sheer number of companies working on their own Hepatitis C treatment.

Given the potential size of this market (pegged at $4 billion by 2009) it is no wonder that pharmaceutical companies are falling all over themselves (and each other) to develop a more viable treatment than currently exists.

I have felt for quite a while that the protease inhibitors were a development to watch. This article gives more more information to illustrate why that is so.

Magic Bullet For Hepatitis C

Scott Gottlieb, M.D., Forbes/Gottlieb Medical Technology Investor, 01.24.05, 10:23 AM ET

When I was a resident in medicine, there was a virus that frightened doctors who had to handle needles and scalpels. Doctors were afraid that in the hurried delivery of emergency care, a hand would slip or a scalpel would fall, and a doctor would accidentally stick herself. If a patient had the virus, chances were good that a doctor could soon have it, too.

But I'm not talking about HIV, the virus that causes AIDS. I'm talking about hepatitis C.

There are about 200 million people in the world who are infected with the hepatitis C virus (HCV)--almost five million in the U.S. alone. The virus causes your liver to swell and stops it from working. Eventually, the liver can become incapable of functioning because constant inflammation kills the organ. HCV is spread by contact with the blood of an infected person, and it is extremely contagious, even more contagious than AIDS.

In industrialized countries, hepatitis C causes 40% of all of the advanced liver disease and 60% of liver cancers. When patients reach these advanced stages, there are not many cures. Short of a liver transplant, many patients with advanced liver disease soon die.

Today, the standard treatment for hepatitis C is the combination of an antiviral medicine that targets the virus and an immune system-boosting drug that helps the body fight the infection. This elixir works for about half of all patients, but many patients can't tolerate the regimen or their bodies don't respond to it.

But there is new hope in the development of a class of drugs known as protease inhibitors. This isn't the same kind of protease inhibitor that has been used to successfully treat AIDS. In the case of HCV, the drug is targeted at a unique kind of protease enzyme only used by the hepatitis C virus.

The most advanced and most promising protease inhibitor for hepatitis C belongs to the Cambridge, Mass.-based biotechnology company Vertex Pharmaceuticals (nasdaq: VRTX - news - people ).

Scientists at Vertex used structure-based drug design to create the drug, known as VX-950. Structure-based design means that scientists use special equipment to make computer models of a three-dimensional structure of the enzyme they are targeting. This enables more rational attempts to design drugs to stick inside the enzyme's active site, by building the ideal drug one atom at a time, like a microscopic Lego set.

The small trial is going to compare the safety and effectiveness of VX-950 to a sugar pill in about 60 healthy volunteers and patients with hepatitis C. The study is expected to finish up this year. It should give Vertex a good look at just how potent the new drug is, as well as a peek at whether it is safe.

If VX-950 works, it will be a big advance for patients with hepatitis C. It could also be a blockbuster medicine--a first-in-class, broad-spectrum antiviral drug that could work for many, if not most, patients infected with hepatitis C. The market for drugs that treat hepatitis C was worth $1.6 billion last year and is expected to grow to $4 billion by 2009.

Doctors have high expectations for this drug class. But there is plenty of caution. At least one other protease inhibitor that was targeted against hepatitis C has failed in development, largely because it had too many side effects.

Keep in mind how protease inhibitors all work. They block an enzyme that belongs exclusively to the hepatitis C virus. There isn't a human protein that is closely related to hepatitis C protease, so the drug should not be interfering with any human cellular processes at all.

That means that the only way these drugs could cause side effects in people is if the liver doesn't break them down very well. This seems to be precisely the problem with older, early formulations of protease inhibitors that were developed by another company, Boehringer Ingelheim. These kinds of problems with metabolism are most often related to the way the drug is designed, not the underlying mechanism of the drug itself.

Schering-Plough (nyse: SGP - news - people ) is also believed to be in early clinical testing with a protease inhibitor of its own that targets hepatitis C. Several other companies have research programs focused on HCV protease inhibitors, including Gilead Sciences (nasdaq: GILD - news - people ), Merck (nyse: MRK - news - people ), Pfizer (nyse: PFE - news - people ), GlaxoSmithKline (nyse: GSK - news - people ) and InterMune (nasdaq: ITMN - news - people ). By all accounts, however, Vertex is farthest along.

There are also some other promising drugs in development for hepatitis C. But the protease inhibitors alone hold out some of the best near-term promise to fulfill the holy grail of hepatitis C therapy--a single potent pill that can destroy the virus all on its own, or in a small cocktail where the drug is used in combination with older medicines.

Vertex thinks it might have found the magic bullet. A clinical trial expected to finish this year could provide doctors, patients and investors with the first sure sign of whether Vertex is right.

Dr. Gottlieb is a practicing physician and a fellow at the American Enterprise Institute. He recently left the FDA, where he was Director of Medical Policy Development and a senior adviser for medical technology to the FDA Commissioner.

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January 22, 2005

Another Hepatitis C Drug Development

The following article is from the Orange County Business Journal. I am posting it for a few reasons. First of all, the article shows that pharmaceutical companies are working hard at coming up with other viable therapies for Hepatitis C. This is enouraging for all us patients.

The second reason is that the article also gives insight into the business of drug development for Hepatitis C and any other disease. The article touches on some of the hows and whys. Valeant is developing Viramidine because their other drug, Ribavirin is losing sales to competitors. They are looking for a replacement drug to slow their loss of sales in the Hepatitis C marketplace. It is a competitive business decision, not a compassionate humanitarian one. Which is okay. Either way they are helping patients. In fact, their desire for profits and business growth is probably a more dependable and powerful motivator than humanitarinaism anyway. It still ultimately works to the patients advantage.

Let's face it, pharmaceutical companies are not non-profit charity organizations, they are businesses. I, for one, have no problem with that---as long as they are ethically looking for better ways to help people get healthy (the key word here is ethically). As patients, though, we need to keep this reality in mind and not think that pharmaceutical companies, or doctors for that matter, are sitting at the right hand of God.

The third reason I'm posting the story is the lawsuit they mention. This woman joined a clinical trial. They key word here is "trial". Right in this description there is a tacit understanding that the risks and rewards of the drug are not entirely known. How could she have ever thought for a moment there was no risk? Even the current approved treatment for Hepatitis C has very serious possible side effects that are clearly outlined before treatment begins.

From my perspective, there is no way she could have thought this was risk-free, unless she was purposely lied to and mislead by the doctors and researchers (which I highly doubt. Remember, Valeant is a business in a high risk industry with lots of litigation. They know their high level of possible liabilities. They get plenty of people to participate without lying, so why would they lie?)

Unless this woman lives on another planet, she had to know there were very real risks involved. People's refusal to take personal responsibility for their own decisions and quickness to blame someone else for their own lapse in judgement has become one of my pet peeves. This seems like another classic case of responsibility avoidance. Yes, it is tragic that she was hurt. But, no one did it to her. She chose to participate in a clinical trial. It was her decision. Nuff said.

Posted date: 1/21/2005

Valeant's Study of Viramidine Drug: Comparable Efficacy to Ribavirin

Drug Is Critical Plank in Growth Strategy

Valeant Pharmaceuticals International said a key drug undergoing testing has proven to be similiarly effective at treating hepatitis C as its fading flagship ribavirin.

The Costa Mesa-based drug maker also said it has enrolled patients in a third-phase study of Viramidine. A filing of a new drug application with the Food and Drug Administration could follow the third phase.

"We are excited about Viramidine's potential and look forward to continuing the phase three pivotal trials, which both finished enrollment in record time," said Chief Executive Timothy Tyson in a release.

Valeant's study, conducted through the liver transplant program at the California Pacific Medical Center in San Francisco, involved 180 patients with chronic hepatitis C.

The company has a lot riding on Viramidine. Ribavirin has been Valeant's key product but has lost sales of late as competiting drugs have taken away sales.

The second-phase trial of Viramidine, meanwhile, has led to a lawsuit against the drug maker from a Bay area woman who alleges she suffered brain damage and permanent disabilities.

In her complaint, Linda Iacovetta said that while seeking treatment for hepatitis C at California Pacific, she was encouraged to be in the trial, which looked at how Viramidine and pegylated interferon worked in concert to fight the liver disease.

Iacovetta's suit said that she was on the drug combination for five months in 2003. She alleged that Valeant and California Pacific doctors who conducted the trial failed to warn users of the risks of taking the drug.

Valeant spokesman Jeff Misakian said earlier this week that Iacovetta's complaint was “completely without merit,” but didn't comment further because it is active litigation.

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January 19, 2005

New Hepatitis C Combination Therapy Looking Good

This press release has more encouraging news for those of us waiting for a more potent and less toxic treatment for Hepatitis C, genotype 1.

Current therapy is least effective for this genotype. Genotype 1 is the most prevalent in the US, Europe and Japan. It is estimated that 70% of Americans are infected with genotype 1 (a or b).

More and more drug therapies are under development as pharmaceutical companies scramble to get a piece of this multi billion dollar market.

While this treatment is still in fairly early stages of testing, the results are nonetheless encouraging.

Encouraging Interim Results of Phase II Study of Valopicitabine (NM-283) in Combination with Peginterferon Alfa in Patients with HCV Genotype 1

The double combination of valopicitabine (NM-283) plus peginterferon alfa produced a 99.94 percent (3.2 log10) mean reduction of HCV RNA (viral load), according to interim results of a Phase II clinical study in treatment-naïve patients with HCV genotype 1. Indenix Pharmaceuticals announced results of the interim analysis, which include data on 19 patients who have completed 12 weeks of combination treatment with valopicitabine plus peginterferon alfa.

Nine of 12 patients receiving combination therapy in this small study experienced an early viral response (EVR) with a greater than 2 log10 decrease in levels of HCV RNA at week 12. No serious adverse events have been reported so far. To date, valopicitabine has demonstrated a satisfactory safety profile with mild to moderate gastrointestinal side effects and no treatment-related discontinuations.

There is a pressing need for more potent and less toxic therapies for the treatment of chronic hepatitis C, especially for individuals with HCV genotypes 1 or 4, who are difficult to treat successfully. Among patients with these two HCV genotypes, only about 50% achieve a sustained virological response (SVR) from use of the current standard of care, peginterferon alfa in combination with ribavirin. Novel new compounds such as valopicitabine offer hope for better outcomes from combination treatment in the future.

An oral nucleoside analog, valopicitabine is Idenix Pharmaceuticals’ lead drug candidate for the treatment of hepatitis C. Now under development in combination with peginterferon alfa, valopicitabine was co-discovered by Idenix and the University of Cagliari through a cooperative laboratory agreement under the direction of Dr. Paolo LaColla, Director of the Department of Biomedical Sciences and Technologies of the University.

“In patients infected with HCV genotype 1 – a difficult-to-treat strain of hepatitis C virus and the most prevalent strain in the U.S., Western Europe and Japan – virologic response to the current standard therapy of ribavirin and peginterferon alfa is inconsistent,” commented Nathaniel Brown, M.D., Idenix’s executive vice president, clinical development and chief medical officer. “However, the consistency of response to the combination of valopicitabine and peginterferon alfa appears promising: eleven of twelve patients receiving this combination treatment had significant HCV RNA reductions of 1.7 to 6.2 log10 by week 12.

Phase IIa Trial Design and 12-Week Interim Results

Based on these encouraging interim data, Idenix will enroll a total of 30 patients in the phase IIa clinical trial, which is designed to assess the safety, antiviral activity and pharmacokinetics of the combination of valopicitabine and peginterferon alfa compared to valopicitabine alone. Key entry criteria for this clinical trial include treatment-naïve patients with HCV genotype 1, baseline viral load greater than 5 log10 copies/ml and alanine aminotransferase (ALT) levels less than 5 times the upper limit of normal.

In this phase IIa clinical trial, patients are being randomized to one of two treatment arms so that 12 patients will receive valopicitabine monotherapy and 18 patients will receive valopicitabine plus peginterferon alfa.. After 12 weeks of treatment, mean HCV RNA reductions from baseline were 0.9 log10 IU/mL, or 87.4 percent, for the 7 patients in the NM283 monotherapy group, and 3.2 log10 IU/mL, or 99.94 percent, for the 12 patients in the combination treatment group.

Nine of twelve patients receiving combination treatment have achieved an early viral response with a greater than 2 log10 decrease in levels of HCV RNA at week 12. Tolerance of both treatment regimens has been satisfactory to date, with no serious adverse events.

Four-week data from a study of these same 19 patients were presented by Dr. Nezam Afdhal at the annual meeting in November 2004 of the American Association for the Study of Liver Diseases (AASLD 2004).

About Hepatitis C

Responses to current treatment options are frequently inadequate due to the inability of some patients to tolerate these treatments and by their limited effectiveness, particularly in patients infected with HCV genotype 1. The genotype 1 strain of HCV is the most treatment-resistant HCV genotype and is estimated to cause more than 70 percent of the reported cases of hepatitis C in the U.S. and Japan, and more than 65% of the reported cases of hepatitis C in Western Europe.

Hepatitis C Drug Development Program at Idenix

Idenix’s hepatitis C development program is initially seeking to address the large patient population that has failed to respond to the current standard treatment, peginterferon alfa plus ribavirin, and for whom no other treatment option is currently available. Idenix expects to subsequently target the treatment-naïve patient population for whom treatment with the current standard of care is only successful in approximately 50% of patients.

“Hepatitis C patients confront many unmet treatment needs, with several hundred thousand having failed prior treatment with no therapeutic options, and millions of people infected with difficult to treat strains of HCV,” said Jean-Pierre Sommadossi, Ph.D., Idenix’s chairman and chief executive officer. “Idenix is committed to rapidly advancing the valopicitabine clinical program, which seeks to address the medical needs of all individuals infected with hepatitis C.”

Drug Development for Patients Who Experience Treatment Failure

Idenix has initiated a Phase IIb clinical trial for valopicitabine in patients who have previously failed peginterferon alfa and ribavirin and expects to begin enrolling patients in this study in early 2005. The company anticipates that this 6-month head-to-head trial, comparing the combination of valopicitabine plus peginterferon alfa to the current standard therapy (ribavirin plus peginterferon alfa), will enroll approximately 170 HCV genotype 1 patients who have previously failed at least 3 months of treatment with current standard therapy. The Phase IIb clinical trial will also include a monotherapy arm of valopicitabine.

Drug Development for Treatment-naïve Patients

Encouraging results from the ongoing Phase IIa clinical trial, summarized above, will support initiation of a larger Phase IIb clinical trial of valopicitabine in combination with peginterferon alfa in treatment-naïve patients, the majority of whom are expected to be infected with HCV genotype 1. Idenix anticipates beginning this trial in mid-2005.

About Idenix

Idenix Pharmaceuticals, Inc. is a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral and other infectious diseases. Idenix’s current focus is on the treatment of infections caused by hepatitis B virus, hepatitis C virus and human immunodeficiency virus (HIV). Idenix’s headquarters are located in Cambridge, Massachusetts and it has drug discovery operations in Montpellier, France and Cagliari, Italy.

Safety, Activity and Pharmacokinetics of the Combination of New Anti-HCV Compound NM-283 Plus Pegylated Interferon

For further information about Idenix, visit http://www.idenix.com/

01/19/05

Source

IDENIX REPORTS INTERIM ANALYSIS OF A PHASE IIA CLINICAL TRIAL OF VALOPICITABINE (NM283) IN COMBINATION WITH PEGYLATED INTERFERON IN TREATMENT-NAÏVE HEPATITIS C GENOTYPE 1 PATIENTS. Press Release. January 10, 2005.

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January 10, 2005

New Hepatitis C Drug (NM283) Clinical Trial Report

This is a report on yet another new drug for the treatment of Hepatitis C. The exciting news for most patients in the US, Europe and Japan is that this drug is specifically targeted toward genotype 1. Genotype 1 is the most common genotype in these areas and is also the hardest to treat with current therapy.

Pharmaceutical companies are rushing to develop new and better treatments for Hepatitis C because they see huge profits. They know that current therapy is inadequate or inappropriate for most patients in the US, Europe and Japan. Ultimately, the greed of the pharma companies works to our benefit.

Incidentally, the results of this trial are apparently very good.

Press Release Source: Idenix Pharmaceuticals, Inc.

Idenix Reports Interim Analysis of a Phase IIa Clinical Trial of Valopicitabine (NM283) in Combination with Pegylated Interferon in Treatment-Naive Hepatitis C Genotype 1 Patients

Monday January 10, 8:30 am ET

Patients receiving the combination treatment achieved a mean viral load reduction of 3.2 log10, or 99.94 percent, after 12 weeks of treatment

SAN FRANCISCO, Calif., Jan. 10 /PRNewswire-FirstCall/ -- Idenix Pharmaceuticals, Inc. (Nasdaq: IDIX - News), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral and other infectious diseases, today announced interim clinical trial data for valopicitabine (NM283), the company's lead drug candidate for the treatment of hepatitis C.

In this phase IIa trial, patients are randomized to one of two treatment arms, valopicitabine (NM283) monotherapy, or valopicitabine (NM283) plus pegylated interferon. This interim data analysis includes all 19 patients who have completed 12 weeks of treatment in this trial. The patients receiving the combination of NM283 and pegylated interferon achieved a mean reduction of serum HCV RNA of 3.2 log10, or 99.94 percent, at week 12.

These data will be included in the company's presentation at the JPMorgan Healthcare Conference on Wednesday, January 12, 2005 at 8:30 a.m. in San Francisco.

"In patients infected with HCV genotype 1 -- a difficult-to-treat strain of hepatitis C virus and the most prevalent strain in the U.S., Western Europe and Japan -- virologic response to the current standard therapy of ribavirin and interferon is inconsistent," commented Nathaniel Brown, M.D., Idenix's executive vice president, clinical development and chief medical officer. "However, the consistency of response to the combination of valopicitabine and interferon appears promising: eleven of twelve patients receiving this combination treatment had significant HCV RNA reductions of 1.7 to 6.2 log10 by week 12.

Based on these encouraging interim data, we have extended this phase IIa trial to 6 months in order to investigate longer duration treatment." Phase IIa Trial Design and 12 Week Interim Results: Idenix will enroll a total of 30 patients in the phase IIa clinical trial, which is designed to assess the safety, antiviral activity and pharmacokinetics of the combination of NM283 and pegylated interferon compared to NM283 alone.

Key entry criteria for this clinical trial include treatment-naive patients with HCV genotype 1, baseline viral load greater than 5 log10 copies/ml and alanine aminotransferase (ALT) levels less than 5 times the upper limit of normal.

In this phase IIa clinical trial, patients are being randomized to one of two treatment arms so that 12 patients will receive NM283 monotherapy and 18 patients will receive NM283 plus pegylated interferon. After 12 weeks of treatment, mean HCV RNA reductions from baseline were 0.9 log10 IU/mL, or 87.4 percent, for the 7 patients in the NM283 monotherapy group, and 3.2 log10 IU/mL, or 99.94 percent, for the 12 patients in the combination treatment group. Nine of twelve patients receiving combination treatment have achieved an early viral response with a greater than 2 log10 decrease in levels of HCV RNA at week 12.

Tolerance of both treatment regimens has been satisfactory to date, with no serious adverse events. Four- week data from these same 19 patients were presented by Dr. Nezam Afdhal at the American Association for the Study of Liver Diseases' annual meeting in November 2004.

Hepatitis C Development Program

Idenix's hepatitis C development program is initially seeking to address the large patient population that has failed to respond to the current standard treatment, pegylated interferon plus ribavirin, and for whom no other treatment option is currently available. Idenix expects to subsequently target the treatment-naive patient population for whom treatment with the current standard of care is only successful in approximately 50% of patients.

"Hepatitis C patients confront many unmet treatment needs, with several hundred thousand having failed prior treatment with no therapeutic options, and millions of people infected with difficult to treat strains of HCV," said Jean-Pierre Sommadossi, Ph.D., Idenix's chairman and chief executive officer. "Idenix is committed to rapidly advancing the NM283 clinical program, which seeks to address the medical needs of all individuals infected with hepatitis C."

Development for Treatment-failure Patients: Idenix has initiated a phase IIb clinical trial for NM283 in patients who have previously failed treatment with pegylated-interferon and ribavirin and expects to begin enrolling patients in this study in early 2005. The company anticipates that this 6- month head-to-head trial, comparing the combination of NM283 plus pegylated interferon to the current standard therapy (ribavirin plus pegylated interferon), will enroll approximately 170 HCV genotype 1 patients who have previously failed at least 3 months of treatment with current standard therapy.

This phase IIb clinical trial will also include a monotherapy arm of NM283. Development for Treatment-naive Patients: Encouraging results from the ongoing phase IIa clinical trial, summarized above, will support initiation of a larger phase IIb clinical trial of valopicitabine (NM283) in combination with pegylated interferon in treatment-naove patients, the majority of whom are expected to be infected with HCV genotype 1. Idenix anticipates beginning this trial in mid-2005.

About Valopicitabine (NM283)

Valopicitabine (NM283) is an oral, novel nucleoside analog that was co- discovered by Idenix and the University of Cagliari through a cooperative laboratory agreement under the direction of Dr. Paolo LaColla, Director of the Department of Biomedical Sciences and Technologies of the University. Valopicitabine (NM283) is being developed in combination with pegylated interferon. To date, valopicitabine (NM283) has demonstrated a satisfactory safety profile with mild to moderate gastrointestinal side effects and no treatment-related discontinuations.

About Hepatitis C

There are approximately 170 million people worldwide with chronic HCV infection, of which approximately 2.7 million are in the United States. Chronic HCV infection accounts for 40 percent of end-stage cirrhosis, 60 percent of liver cancer and 30 to 40 percent of liver transplants in the United States and other industrialized countries. Responses to current treatment options are frequently inadequate due to the inability of some patients to tolerate these treatments and by their limited effectiveness, particularly in patients infected with HCV genotype 1.

The genotype 1 strain of HCV is the most treatment-resistant HCV genotype and is estimated to cause more than 70 percent of the reported cases of hepatitis C in the U.S. and Japan, and more than 65% of the reported cases of hepatitis C in Western Europe.

About Idenix

Idenix's headquarters are located in Cambridge, Massachusetts and it has drug discovery operations in Montpellier, France and Cagliari, Italy. For further information about Idenix, please refer to http://www.idenix.com.

Forward-looking Statements

This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Act of 1995. Statements in this press release other than those that are historical in nature are "forward- looking statements."

Such forward looking statements, which include statements with respect to the potential therapeutic benefits and successful development of the company's drug candidates and the company's drug discovery, research and clinical development activities, are subject to numerous factors, risks and uncertainties that may cause actual events or results to differ materially from the company's current expectations. These risks and uncertainties relate to the results of clinical trials and other studies with respect to the drug candidates that the company has under development; the timing and success of submission, acceptance and approval of regulatory filings; the company's dependence on its collaboration with Novartis Pharma AG; the company's ability to obtain additional funding required to conduct its research, development and commercialization activities; the ability of the company to attract and retain qualified personnel, and the company's ability to obtain, maintain and enforce patent and other intellectual property protection for its drug candidates and its discoveries.

These and other risks are described in greater detail in the "Risk Factors" section of the company's quarterly report on Form 10-Q for the quarter ended September 30, 2004 and filed with the Securities and Exchange Commission and other filings that the company makes with the Securities and Exchange Commission.

All forward-looking statements reflect the company's expectations only as of the date of this release and should not be relied upon as reflecting the company's views, expectations or beliefs at any date subsequent to the date of this release. Idenix anticipates that subsequent events and developments may cause these views, expectations and beliefs to change. However, while Idenix may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so.

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December 29, 2004

New Early Liver Disease Test

This article from the BBC speaks of a new test to detect fibrosis/cirrhosis markers. It represents just one more advance in the diagnosis and treatment of liver disease.

It is especially valuable to note that this test is non-invasive.

Test to spot early liver disease.

Technique could lead to a blood test.

A technique for identifying early liver damage could help improve detection of the deadly condition cirrhosis.

Essex University scientists teamed up with a German team to pinpoint a group of biochemical markers that indicate the disease is in its early stages.

The markers are made up of debris from damage to proteins, a well-known early sign of cirrhosis.

The Journal of Hepatology study could lead to a blood test to detect damage earlier, and stop progression.

Lead researcher Professor Paul Thornalley, who led the research, said: "It is likely that debris from this damage, leaking into the blood, will prove a novel biochemical test for early liver damage."

Cirrhosis kills an estimated 4,000 people in the UK each year. Over the last 20 years, there has been a massive increase in the numbers killed by liver damage, with fatalities among men up 121% since the early 1980s and among women by around 68%.

The disease is most commonly associated with alcohol but it can also affect anyone infected with hepatitis C.

Up to 15% of chronic alcoholics develop alcoholic cirrhosis, of whom 75% will eventually die through liver damage.

Scarred tissue

It begins with the formation of scarring, known as fibrous tissue.

Left unchecked, this can gradually develop into full-blown cirrhosis, for which the only treatment is a transplant. However, there is a national shortage of donor organs.

A test that could pick up early liver damage could help identify hepatitis C sufferers and also be used to monitor whether patients are following doctors' instructions to abstain from alcohol.

The new marker is a by-product of the destruction of proteins in the liver. This destruction takes place as disease sets in.

Tests showed a 15-fold increase in the level of this marker in cases where scarring of the liver was underway.

Although the test does not differentiate between alcohol damage and other causes, it could still be used to check progress of drink-related disease.

Abstinence test

Professor Thornalley said: "Alcohol represents 50% of cirrhotic livers in the UK.

"This test could be an indication of whether people are sticking to their abstinence programmes.

"People have been looking for such a marker for many years. We've not seen one that changes so dramatically as this."

Charles Gore, of the Hepatitis C Trust, said if the test showed liver damage then patients could be given drugs to rid the body of the hepatitis virus.

But he said he doubted it would make a huge difference, because liver disease progressed so slowly treatment may not be immediately necessary.

"Damage from hepatitis C is very slow. The disease may be setting in but it could be 10 years before something happens."

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December 21, 2004

Experimental Stem Cell Therapy for Cirrhosis

Cirrhosis is still officially considered an irreversible condition. Some experiments have shown natural substances like milk thistle (especially Maximum Milk Thistle) can slow or possibly even reverse fibrosis (the process that leads to cirrhosis).

Now, scientists are utilizing stem cells to repair damaged livers. This appears to be regardless of the cause of cirrhosis (alcoholic induced hepatitis or viral hepatitis).

These are the kinds of experiments that offer real hope to people with serious liver concerns.

Reading between the lines in the report from the medical journal "Hepatology" gives us some interesting data. One fact that stands out is that 25 million Americans (one in ten) have liver related diseases---making this the seventh leading cause of death.

Another fact stated is that 10,000 Hepatitis C patients die due to cirrhosis each year, and another 5,000 from chronic Hepatitis B.

Clearly, it is important to protect and support your liver. While a small minority of Hepatitis C patients will progress to end stage liver disease (just 20 to 30% according to the Centers for Disease Control), this is a very serious life-threatening condition for those most negatively affected.

A pioneering stem cell therapy designed to heal otherwise irreversible liver damage has started trials in Japan. A similar trial on people with cirrhosis is about to start in London, UK.

The need for new treatments is urgent. Cirrhosis kills 27,000 Americans each year, and one in 10 of the population - 25 million Americans - have liver-related diseases making it the seventh most common cause of death. For now, the only real hope for patients who suffer severe liver damage through heavy drinking or viral infections is a liver transplant from a matched donor. But waiting lists for livers are growing.

In the U.S., 18,500 patients await transplants. In the UK, the waiting list has more than doubled between 1994 and 2003, from 101 to 239, although around 600 people a year receive a transplant.

Antiviral drugs tackle viral-related cirrhosis if given in time, but sometimes the damage is too advanced, resulting in up to 10,000 cirrhosis deaths from hepatitis C in the US, and 5000 deaths from hepatitis B.

Younger drinkers

The situation is just as dire in the UK, where cirrhosis cases are increasing, according to Alison Rogers, chief executive of the British Liver Trust. Alcohol-related cirrhosis accounts for around half of cases.

"People are drinking more, and younger than they used to, and women are drinking more," says Rogers. Extrapolating from a recent, unpublished study of hepatitis C prevalence in Southampton, Rogers says that as many as 750,000 drug users in the UK could be harbouring the virus.

The pioneering Japanese trial builds on successful experiments with mice. "Our results showed that even if chronic liver injury exists, transplantation of bone marrow stem cells can reverse this," says Isao Sakaida of Yamaguchi University in western Japan, head of the team that developed the new procedure. He says it is too soon to know if people in the trial are responding to the treatment.

For their mouse experiments, Sakaida and his team damaged the livers of the animals by injecting carbon tetrachloride, to produce a condition called liver fibrosis in which interconnected strands and patches of damaged and dead tissue criss-cross the organ. Fibrosis eventually develops into cirrhosis when nodules of cells form at the junctions of the fibrous strands.

After four weeks, Sakaida took bone marrow cells from donor mice that had a jellyfish gene inserted to make their cells glow green. He then injected the cells into the tail veins of half the mice with damaged livers. Sakaida was able to track where the glowing cells ended up in the liver-damaged mice. In the fifth and eighth weeks of the experiment he found the cells had migrated en masse to the liver.

"Ready to go"

Following the infusion of bone marrow cells, the proportion of fibrous tissue in the liver shrank from an average of nearly 5.4% in the fifth week to less than 4.2% three weeks later. Mice in a control group given only saline solution showed no such change.

The team were able to show that bone marrow cells reaching the liver changed into liver cells and made large amounts of an enzyme called matrix-metalloproteinase-9 (MMP-9), which may play a role in dissolving fibrotic tissue.

For the trials on people, Sakaida's team favours injecting bone marrow stem cells extracted from the patients themselves to avoid problems of rejection of donor cells. At Hammersmith Hospital in London, a team headed by Nagy Habib claims to be "ready to go" with a similar trial. The London team plans to concentrate stem cells obtained from the patients' bone marrow and inject them into the liver through the hepatic portal vein.

Both techniques risk quite serious side effects. Some bone marrow cells, for example, might form scar tissue, making the cirrhosis worse. But Habib says the Japanese work in mice indicates that this is unlikely.

Further question marks arise from an almost identical study published last year in Proceedings of the National Academy of Sciences (vol 100, p 11850) by Inder Verma and Yoshiyuki Kanazawa of the Salk Institute for Biological Studies in La Jolla, California, US. They found hardly any evidence of healed liver tissue after they infused bone marrow cells, and concluded that "bone-marrow derived cells cannot generally lead to a cure for liver damage".

Journal reference: Hepatology (vol 40, p 1304)

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December 13, 2004

Weight-based treatment dosing for Hepatitis C

The following article is from hepatitisneighborhood.com, a website of priorityhealthcare.com.

While the basic information in this article is very enlightening, I also like to read between the lines.

What is most relevant here? First of all, that the study focused on genotype 1 (the most common in North America, with approximately 70% of patients). The study verified that genotype 1 is hardest to treat with current conventional (read, interferon) therapy.

Next, I find it very telling that the response was TWICE AS GOOD with weight based dosing. That begs the question---why isn't everyone with genotype 1 treated based on weight?

Then, I found it very telling that even at the best-possible response they did no better than 29 percent of patients with SVR (with only a measily 16% at standard dosing).

Then, they talk about relapses. So, as I understand it, 29% responded but then 22% of them relapsed. So, isn't that a success rate that is closer to just 20% of patients, even with the superior weight dosing?

Finally we have the side-effects information. Wow! Discontinuation for adverse events were nearly neck and neck at 18% vs 17%. So, if that were the only criteria, I'd certainly choose weight based dosing (whether African American or not). However, If 29% responded, but 22% of them relapsed and 18% dropped out due to adverse effects, how many were actually helped?

Food for thought, don't you agree?

African-Americans with Hepatitis May Benefit More from Weight-Based Ribavirin

by John C. Martin
Article Date: 12-08-04

A new, large study finds that African-Americans diagnosed with hepatitis C (HCV) respond better to treatment when the antiviral drug, ribavirin, is dosed based on weight rather than standardized.1

Lower SVR Found
Previous studies have found that African-Americans with HCV have lower response rates to treatment compared to other ethnic groups for unknown reasons.2,3 In hepatitis C, there are several genotypes, or species, of virus that can infect any one person. Studies have found that genotype 1, which also happens to be the most common, is the most difficult to treat.4,5

But "the high prevalence of HCV genotype 1 is insufficient to explain the low SVR [sustained virologic response] rates in this population," write Ira Jacobsen, MD, in the department of Gastroenterology & Hepatology at Cornell University, and his colleagues.

How Does Ribavirin Impact SVR Rates?

So, Jacobson and his team set out to determine African-Americans' response to combination therapy using peginterferon alfa-2b (PEG-Intron/Schering-Plough) with ribavirin, as well as to determine the optimal dose of ribavirin in this group. Of 5000 patients who were selected at random to receive peginterferon alfa-2b with either weight-based doses or fixed doses of ribavirin, 387 African-Americans with genotype 1 HCV were analyzed for this study. All the patients were taking part in an unrelated clinical study.

Three hundred sixty-two patients who weighed more than 65 kg (143 lbs) received 1.5 micrograms (mcg) of peginterferon alfa-2b per kilogram of body weight (1.5 µg/kg) once per week combined with either a standard dose of 800 milligrams (mg) of ribavirin, or a weight-based dose of 800 to 1400 mg. The criteria were as follows:

• Those weighing less than 143 lbs (less than 65 kg) received 800 mg
• Those weighing between 143 lbs and 187 lbs (65-85 kg) received 1000 mg
• Those weighing between 189 lbs and 229 lbs (86-104 kg) received 1,200 mg
• Those weighing between 231 lbs and 273 lbs (105-124 kg) received 1,400 mg

Therapy lasted for a total of 48 weeks, with 6 months of post-treatment follow-up. Patients who remain virus-free for a minimum of 6 months following the end of therapy are considered to have achieved a sustained virologic response (SVR) to the treatment.6

After the follow-up period, it was found that twice as many African-American patients who received weight-based ribavirin doses responded to therapy compared to those who were given the standard dose. Of 174 patients who received weight-based doses, 29 percent responded. That compares to only 16 percent of those who received the standard 800 mg dose, Jacobson and his associates reported, a difference they considered significant. Further, relapses occurred in 22 percent of patients receiving weight-based ribavirin versus nearly a third of those who received standard doses, they wrote.

Dealing with Ribavirin Side Effects

Anemia—a common side effect of ribavirin—was more common in those who received weight-based dosing, they noted (47 percent of those taking weight-based doses had anemia compared to 29 percent of those on the fixed dose). As a result, "dose reductions of ribavirin (12% v 8%) and erythropoietin use were more common with weight-based dosing, but overall safety for the two groups was similar," the researchers wrote. "Discontinuations for adverse events were 18% in weight-based dosing and 17% for standard dosing, with 25 severe adverse events in each group."

Erythropoietin is a hormone that helps regulate red blood cell production in the body. It is also used as an anemia treatment.

"Weight-based dosing of ribavirin offers a significant advantage in the treatment of African-American patients infected with HCV genotype 1," the study investigators concluded.

1. Jacobson I, Brown R Jr., McCone J et al. Weight based ribavirin dosing improves virologic response in HCV-infected genotype 1 African-Americans (AA) compared to flat dose ribavirin with peginterferon alfa-2b combination therapy. 55th Annual Meeting of the American Association for the Study of Liver Diseases. 2004 Oct 29-Nov 2. Boston, MA.
2. Muir AJ, Bornstein JD, Killenberg PG; Atlantic Coast Hepatitis Treatment Group. Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N Engl J Med 2004 May 27;350(22):2265-71.
3. McHutchinson JG, Poynard T, Pianko S et al. The impact of interferon plus ribavirin on response to therapy in black patients with chronic hepatitis C. The International Hepatitis Interventional Therapy Group. Gastroenterology 2000 Nov;119(5):1317-23.
4. Trepo C. Genotype and viral load as prognostic indicators in the treatment of hepatitis C. J Viral Hepat 2000 Jul;7(4):250-7.
5. Fried MW. Viral factors affecting the outcome of therapy for chronic hepatitis C. Rev Gastroenterol Disord 2004;4 Suppl 1:S8-S13.
6. Berg T, Kronenberger B, Hinrichsen H et al. Triple therapy with amantadine in treatment-naïve patients with chronic hepatitis C: a placebo-controlled trial. Hepatology 2003 Jun;37(6):1359-67.

John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.

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December 07, 2004

BILN 2061 For Hepatitis C Revisited

We have reported on BILN 2061 before because of its exciting promise as a Hepatitis C therapy. Unfortunately, testing has been suspended because of animal studies that indicated possible cardiac toxicity with the substance.

The November issue of the medical journal, Gastroenterology, further reported on the promising results and also mentioned the subsequent suspension of human studies.

We will keep you posted on any change or progress we hear of regarding BILN 2061.

Further Human Trials of BILN 2061 on Hold Pending Resolution of Animal Toxicity Issues

Novel, potent, and well-tolerated hepatitis C virus (HCV) drugs are needed. BILN 2061 is a potent and specific inhibitor of HCV serine protease in vitro. Preclinical toxicology data and studies in healthy volunteers supported the administration of BILN 2061 to patients with HCV infection.

The antiviral efficacy, pharmacokinetics, and tolerability of 25, 200, and 500 mg BILN 2061 twice daily given as monotherapy for 2 days in 31 patients infected with chronic genotype 1 HCV infection and with minimal liver fibrosis (Ishak score of 0–2) were assessed in a placebo-controlled, double-blind pilot study.

In 2 subsequent placebo-controlled studies of similar design, 200 mg BILN 2061 twice daily was administered for 2 days to 10 patients with advanced liver fibrosis (Ishak score of 3 or 4) and to 10 patients with compensated cirrhosis (Ishak score of 5 or 6).

Results

Viral RNA reductions of 2–3 log10 copies/mL were achieved in most of the patients. There was a trend toward a higher number of patients receiving 500 mg BILN 2061 achieving a viral RNA reduction ≥3 log10 copies/mL as compared with patients receiving 25 mg BILN 2061.

Advanced fibrosis or compensated cirrhosis did not affect the antiviral efficacy of BILN 2061. BILN 2061 was well tolerated in all studies.

Conclusions

The authors conclude, “BILN 2061 is a well-tolerated and very active compound that reduced serum viral RNA concentrations after 2 days of treatment in patients infected with genotype 1 HCV independent of the degree of fibrosis. Nevertheless, further clinical trials are on hold pending resolution of animal toxicity issues.”

12/01/04

Reference
H Hinrichsen and others. Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype 1 patients. Gastroenterology 127(5): 1347-1355. November 2004.

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November 22, 2004

Hepatitis C Treatment Progress?

The following announcement from Rigel Pharmaceuticals is disappointing. It is another step closer to a more effective treatment, but, on its own, it shows no breakthrough. In fact, the treatment needs to be rethought because of its minimal effectiveness.

Well, at least it seems safe.

Some of the most interesting information in pharmaceutical company announcements is regarding hepatitis C itself and the state of current treatment. Look at the "About Hepatitis C" section of the report. It clearly points out the shortcomings of current interferon combination therapy.

If you are currently considering therapy, you may want to share this with your doctor, to help keep the limited effectiveness and serious dangers of combination therapy in perspective.

Poor Bioavailability Results in Insignificant Clinical Effects for Rigel R803 in Phase I/II HCV Trial
Monday November 22, 5:00 am ET

Next Steps for Clinical Program to be Outlined at Analyst Day, December 1st

SOUTH SAN FRANCISCO, Calif., Nov. 22 /PRNewswire-FirstCall/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL - News) announced today the results from its Phase I/II clinical study of R803, a novel oral hepatitis C RNA polymerase inhibitor. The two-center, double-blind, dose-escalation study examined the safety and pharmacokinetics of R803 and its effectiveness in reducing viral levels in 32 patients infected with Hepatitis C Virus (HCV). The results demonstrated that R803 was well-tolerated and that there were no significant adverse effects. The study showed that the drug was only present in the blood stream at sufficient levels for a limited number of hours during the course of each dosing day. There was a decline in viral levels over the course of treatment and viral levels rose after dosing was discontinued. However, the decline in viral levels was not statistically significant or clinically meaningful. Rigel has continued to develop better delivery approaches of R803, such as a pro-drug of R803, and derivatives of R803 that it believes exhibit superior bioavailability. These potential improvements and next steps in the Rigel HCV clinical program will be discussed at Rigel's analyst day meeting in New York City on December 1, 2004.

"These results, although disappointing, have provided us with very useful clinical information on the improvements necessary to achieve significant results in HCV infection." said James M. Gower, chairman and CEO, Rigel Pharmaceuticals. "We have learned a great deal about how R803 is metabolized and its bioavailability. While viral loads were not meaningfully reduced, we believe that with an R803 pro-drug or derivatives the pharmacokinetics and drug exposure could be improved. We believe we have identified drug candidates with improved bioavailability and good anti-viral activity for our HCV program. We will be studying these issues in detail over the next several weeks before deciding on our future clinical direction."

R803 Phase I/II Clinical Trial Design

The study was a 32 patient Phase I/II randomized, placebo-controlled, double-blind multiple, dose escalation study, which took place in Miami and New Orleans. The objectives of the study were to evaluate the safety and pharmacokinetics of R803 in patients with HCV and to explore the effectiveness of R803 in reducing viral levels. Patients were divided into eight groups, with each group receiving an increasing dose or increasing number of days of treatment. Subjects were dosed for two to four days, plus the morning dose on the following day. HCV viral RNA levels were measured multiple time levels following the administration of R803.

About Hepatitis C

Hepatitis C is an inflammation of the liver caused by the hepatitis C virus. As the most common blood-borne infection in the U.S., HCV affects 4 million Americans and 170 million individuals worldwide. It is estimated that this difficult-to-treat disease, with 6 genotypes and no vaccine, will dramatically increase in prevalence. The disease is caused by an infection of hepatic cells by an RNA virus of the Flavivirus family. Approximately 85 percent of those with acute illness will go on to develop chronic hepatitis, a condition that has been linked to cirrhosis, hepatocellular carcinoma (liver cancer) and liver failure. HCV accounts for 30 percent of end-stage liver disease and liver cancer and is the leading cause of liver failure, which can result in the need for liver transplantation.

Current HCV Treatments and Market Opportunity

Currently available HCV therapies are only modestly effective at treating the disease. The most prevalent treatment regimen is with pegylated interferon alpha (IFN), usually in combination with ribavarin. IFN shows only an approximate 40 percent success rate in patients who complete therapy, and significant side effects result in up to half the patients either quitting treatment or moving to a lower dose regimen. Moreover, IFN is least effective against HCV genotype 1, the strain responsible for 70 percent of chronic HCV infection cases in the U.S. Rigel believes that its approach is substantially different than that of IFN: instead of working to boost the immune system, experiments indicate that its HCV compounds directly, rapidly, and selectively target HCV by interfering with a viral polymerase protein that is needed for replication. With the current high prevalence and projected increase in cases of HCV and related diseases, and with the limited success of currently available therapies, Rigel believes that the potential for new direct HCV therapeutics is large.

About Rigel (www.rigel.com)

Rigel's mission is to become a source of novel, small-molecule drugs to address large, unmet medical needs. We have initiated four development programs: asthma/allergy, hepatitis C, rheumatoid arthritis and oncology. Rigel has begun clinical testing of its first two product candidates, R112 for allergic rhinitis, which has completed a Phase II clinical trial, and R803 for hepatitis C, as discussed in this release. We expect to begin clinical trials of R406 for the treatment of rheumatoid arthritis by the end of 2004, to be followed by the anticipated initiation of clinical trials with additional product candidates for indications in oncology and asthma.

Information on the webcast of Rigel's analyst day presentation on December 1, 2004 is available on Rigel's website: www.rigel.com

Forward Looking Statements

This press release contains "forward-looking" statements, including statements related to Rigel's plans to evaluate alternative delivery approaches for R803 and derivatives of R803 and the potential efficacy thereof, the clinical development of product candidates and the timing thereof and the potential efficacy of product candidates. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "will," "plans," "intends," "expects" and similar expressions are intended to identify these forward-looking statements. There are a number of important factors that could cause Rigel's results to differ materially from those indicated by these forward-looking statements, including the risks associated with the timing and success of clinical trials and the commercialization of product candidates, as well as other risks detailed from time to time in Rigel's SEC reports, including its Quarterly Report on Form 10-Q for the quarter ended September 30, 2004. Rigel does not undertake any obligation to update forward-looking statements.

Source: Rigel Pharmaceuticals, Inc.

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November 11, 2004

New Treatment From Vertex in Trials

Here is another new treatment in testing for Hepatitis C. The pharmaceutical companies are scrambling to develop more effective treatments than those currently available.

With hundreds of millions of Hepatitis C patients around the world, the drug companies see a gold mine in developing treatments.

It may be greed-driven but it still offers real hope to Hepatitis patients everywhere.

Vertex begins phase Ib hepatitis C trial

Global biotech firm Vertex Pharmaceuticals (NASDAQ: VRTX - news) , a small-molecule drugs developer, has initiated a phase Ib clinical trial for its investigational oral protease inhibitor for the treatment of hepatitis C infection.

Global biotech firm Vertex Pharmaceuticals, a small-molecule drugs developer, has initiated a phase Ib clinical trial for its investigational oral protease inhibitor for the treatment of hepatitis C infection.

The double-blind, placebo-controlled study will evaluate the tolerability, pharmacokinetics and viral kinetics of multiple, ascending doses of VX-950 over a period of up to 14 days and will enroll approximately 60 subjects. This is the first reported initiation of a study that involves 14 days of administration of a hepatitis C virus (HCV) protease inhibitor in patients with chronic hepatitis C infection.

The clinical study will first assess healthy volunteers receiving multiple doses of VX-950 for a five-day period. Following this initial assessment, the study will evaluate three different doses of VX-950 in HCV patients, over 14 days of treatment in serially configured dose groups.

Pre-clinical studies have shown that VX-950 significantly reduces levels of HCV RNA in both an in vitro replicon system and infectious virus assays. In the phase Ia clinical study, VX-950 was well-tolerated and demonstrated oral bioavailability.

Furthermore, combined clinical and pre-clinical pharmacokinetic results indicate that VX-950 can be administered in a dose regimen that may achieve liver concentrations substantially greater than target concentrations (IC50 and IC90 in non-clinical studies).

"The phase Ib study is expected to provide us with important information on the ability of VX-950 to reduce viral load, which we expect will help to define the potential clinical impact of this new class of drugs," said Dr John Alam, senior vice president of drug evaluation and approval at Vertex.

Vertex anticipates that the phase Ib study will be completed in the first half of 2005.

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November 01, 2004

Pegasys Better Than PegIntron?

From the following article it seems there is a real advantage for Hepatitis c patients to choose Pegasys from Roche over PegIntron from Schering. The higher early response rates are encouraging. Of course, this is still comparing the best of two treatements that are considered by most people to be inadequate.

If one is deciding to undergo treatment for Hepatitis c, however, it is helpful to know that one choice might be better than another. Even if the difference is miniscule, any positive difference is important.

Bear in mind, this is just one study. Most researchers would not find this conclusive, just instructive.

If I were to choose to undergo interferon treatment for Hepatitis c (NOT currently on my list of things to do seeing as the success rate for genotype 1 is so miserably low) I would probably choose Pegasys for other reasons (I think Roche's patient support is better, for one). This recent information only reinforces the preference.

Drug Combination Shows Promise in Treating Hepatitis C

ST. LOUIS--October 30, 2004 -- Interim study results indicate a certain drug combination treatment may suppress the hepatitis C virus more quickly than another.

Researchers at Saint Louis University School of Medicine and six other research sites throughout the country found that combining the drug Pegasys® with ribavirin resulted in a greater reduction in hepatitis C viral levels than patients treated with Peg-Intron® and an equal dose of ribavirin.

Pegasys and Peg-Intron are types of pegylated alpha interferon--which is a longer lasting version of interferon, a naturally produced substance in the body that triggers the immune system. Combining these drugs with ribavirin enhances their efficacy and is the standard treatment for hepatitis C.

"It looks as though Pegasys is more potent during the early phase of treatment, which is critical for patients with chronic hepatitis C," said Adrian M. Di Bisceglie, M.D., professor of internal medicine in Saint Louis University School of Medicine's division of gastroenterology and hepatology, and the study's lead investigator. "It's critical because if patients are going to respond to treatment, it will happen during the first 12 weeks of care. Eight weeks into this trial we noticed lower viral levels in patients on the combination of Pegasys and ribavirin."

This is one of the first head-to-head studies in the United States comparing Pegasys and Peg-Intron when each are combined with equal doses of ribavirin. Pegasys is the most recent form of pegylated alpha interferon approved by the Food and Drug Administration (2002).

Di Bisceglie helped design the study and evaluate the preliminary results.

Di Bisceglie will present his findings at the 55th annual meeting of the American Association for the Study of Liver Diseases in Boston on Oct. 29.

Di Bisceglie said the ultimate goal of therapy is to clear patients of the blood-borne virus or have levels drop so low as to be undetectable. While the Pegasys results are positive, Di Bisceglie cautioned it is too soon to draw conclusions. The 12-week trial is still under way.

"Studies such as this one give us insight into how these drugs work and it might allow us to design better drugs in the future," said Dr. Di Bisceglie, one of the top liver disease experts in the world.

About 4 million Americans carry antibodies to the infection, which means they have been exposed to hepatitis C. Of that group, about 70 percent actually have the virus and will become symptomatic. The symptoms at first may be subtle: fatigue, abdominal discomfort, general malaise. While carriers ignore or misinterpret symptoms, the virus is eating away at their livers. If left undetected or untreated, chronic hepatitis C irrevocably damages the liver and a transplant may be necessary. Saint Louis University School of Medicine has one of the largest hepatitis C treatment and research programs in the country.

Source: Saint Louis University

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October 24, 2004

Two New Interferon Studies from Schering

Perhaps the most telling part of the following announcment is the acknowledgment of the fact that genotype is one of the key factors in determining current treatment success rates. And the most common genotype for 70% of people is also the most resistant to current treatment.

Of course, if Schering can show that longer treatment gives a higher success rate then they can sell more Pegintron plus Rebetol. Be sure to note that they are not concurrently checking to see what effect sustained use of their product might have on the patient with regard to side-effects. Not a surprising fact, but still noteworthy.

The second study being initiated is to determine whether or not Schering's product could help people that the Roche product could not. Schering has nothing to lose on this one. If their product doesn't help, it is no worse a result than Roche's. If it does work they can claim superiority (and also sell a lot more product to those who did not respond to Pegasys).

Also noteworthy is the fact that according to Professor Stefan Zeuzem, M.D. the therapeutic goal of the medical community is "eradication of the virus". This is in spite of the fact that 70-80% of people will never face life threatening ramifications from chronic Hepatitis c. Instead of finding ways to protect and support the liver and immune system until a more viable (and less toxic) treatment is found, the medical community is intent on "eradication" at almost any cost. Could it be because there is less money in fortification than there is in pharmaceutical treatment? I don't know, what do you think?

Schering-Plough Initiates Two Major Hepatitis C Studies With PegIntron(R) Plus Rebetol(R) Combination Therapy

BRUSSELS, October 22 /PRNewswire/ --

- International Clinical Trials To Assess PegIntron in Patients with Unmet Medical Needs

Schering-Plough announced today that it is initiating two large international clinical trials to evaluate the use of PegIntron(R) (peginterferon alfa-2b) and Rebetol(R) (ribavirin) combination therapy in patients chronically infected with hepatitis C virus (HCV) genotype 1 who have specific unmet medical needs.

The first study will involve patients identified as "slow" responders to HCV therapy; the second study will involve patients who were non-responders to previous treatment with Pegasys (peginterferon alfa-2a) plus Copegus (ribavirin) (Hoffmann-La Roche, Inc.) combination therapy. Currently, there are no approved products for treating these patient populations.

"We have made great advances over the past decade in the effective treatment of chronic hepatitis C, one of the most common blood borne infections in the world," said Robert J. Spiegel, M.D., chief medical officer and senior vice president of medical affairs, Schering-Plough Research Institute. "Still, specific patient populations with difficult-to-treat forms of the disease remain resistant to therapy and need improved treatment options. Schering-Plough is undertaking these studies because it is critical to develop new strategies for improving treatment outcomes for these patients."

Of the six distinct known hepatitis C genotypes, HCV genotype 1 is the most common worldwide (about 70% of patients). It is considered the most difficult-to-treat strain of the virus and is associated with higher resistance to treatment (lower response rates) when compared with HCV genotypes 2 and 3.

Adjusting Treatment Duration for "Slow" Responders

Schering-Plough is sponsoring the SUCCESS trial: "A Study to Assess Treatment with PegIntron and Rebetol in Naïve Patients with Genotype 1 Chronic Hepatitis C and Slow Virological Response," that will evaluate whether extending treatment to 72 weeks instead of the standard 48 weeks will improve efficacy in genotype 1 chronic hepatitis C patients who respond slowly to treatment. Slow responders are defined as those patients who still have detectable virus levels after 12 weeks of treatment (PCR positive), but do show a significant (2 log10) drop in viral load. Such patients may ultimately achieve undetectable virus levels (PCR negative) between weeks 12 and 24, and may benefit from a longer overall course of therapy (72 weeks) than the current recommended duration of 48 weeks.

This prospective, controlled, randomized, parallel-group multicenter study is expected to enroll 1,200 previously untreated patients with chronic hepatitis C at more than 100 sites in Europe, Eastern Europe, Israel and Canada. The study hypothesis is that patients who become HCV-RNA negative (achieve undetectable levels of the virus) between treatment weeks 12 and 24 (slow responders) may need a longer period with undetectable virus to successfully clear the virus and ultimately achieve a sustained virologic response (SVR). SVR is defined as having undetectable virus 24 weeks after completing therapy. In the study, patients who achieve a late response to therapy (as measured at week 24) will be randomized at the end of 48 weeks of therapy with 1:1 ratio to either stop treatment or extend the trial to 72 weeks.

"Success in treating patients with chronic hepatitis C depends on a number of factors, with genotype considered one of the most important predictors for achieving sustained virologic response," said Professor Maria Buti Ferret, M.D., co-lead investigator of the study with Professor Rafael Esteban Mur, M.D., both of Vall d'Hebron Hospital, Barcelona, Spain. "We know from previous clinical studies that patients with HCV genotype 2 or 3 can achieve SVR with shorter 24-week courses of treatment. Conversely, this study will help us to determine if a longer 72-week course of PegIntron and Rebetol benefits those patients with difficult-to-treat genotype 1 who are slow to respond."

PegIntron plus Rebetol in Non-Responders to Pegasys plus Ribavirin

In the ESPECIAL trial: "Efficacy and Safety of PegIntron plus Rebetol in Subjects with Chronic Hepatitis C Genotype 1 Non-Responder to Pegasys plus Ribavirin," patients infected with HCV genotype 1 who did not respond or relapsed following an initial course of treatment with Pegasys (180 mcg/wk) plus Copegus (1,000/1,200 mg/day) will be treated with weight-based PegIntron (1.5 mcg/kg/wk) plus Rebetol (800-1,400 mg/day) combination therapy for 48 weeks. This international multicenter clinical trial will involve 200 patients.

"The therapeutic goal of treatment for chronic hepatitis C is the eradication of the virus with a halt in the progression of the disease," said Professor Stefan Zeuzem, M.D., Saarland University, Homburg, Germany, and lead investigator of the study. "We need effective alternatives for the sizable number of patients who did not clear the virus with initial treatment. PegIntron and Pegasys are different drugs, with different pharmacokinetic and pharmacodynamic properties. Patients who did not respond or relapsed to Pegasys plus Copegus may respond to PegIntron plus Rebetol," he said.

The primary endpoint of the study will be the proportion of patients who have achieved sustained virological response (SVR) at 24 weeks after the end of treatment. Secondary endpoints of the study include early virological response (EVR), defined as undetectable virus levels (PCR negative) at week 12 of treatment; the response rate at the end of 48 weeks of treatment (EOT); and sustained virological response (SVR) rates based on subject weight, viral load, presence of cirrhosis, insulin resistance status and creatinine clearance status.

The SUCCESS and ESPECIAL trials are consistent with Schering-Plough's research strategy to conduct and support clinical studies with weight-based PegIntron and Rebetol combination therapy in hepatitis patients with unmet medical needs, particularly for better efficacy in patients with difficult-to-treat forms of the disease such as HCV genotype 1, the most common genotype worldwide.

About PegIntron and Rebetol Combination Therapy

PegIntron and Rebetol combination therapy for chronic hepatitis C was approved in the European Union (EU) in March 2001, and is indicated in naïve patients as well as in patients who have previously responded to interferon alpha monotherapy but who have subsequently relapsed. PegIntron is indicated in the EU as a monotherapy in cases of intolerance or contraindication to ribavirin for the treatment of adult patients with chronic hepatitis C. The recommended dose in the EU for combination therapy is PegIntron 1.5 mcg/kg once weekly plus Rebetol 800-1,200 mg daily, adjusted to body weight.

PegIntron, recombinant interferon alfa-2b linked to a 12,000 dalton polyethylene glycol (PEG) molecule, is a once-weekly therapy dosed according to patient body weight that is designed to achieve an effective balance between antiviral activity and elimination half-life. Rebetol is an oral formulation of ribavirin, a synthetic nucleoside analog with broad-spectrum antiviral activity.

Chronic hepatitis C is estimated to affect more than 10 million people in major world markets. In Europe, chronic hepatitis C is a leading cause of chronic liver disease and one of the most common reasons for liver transplant.

Schering-Plough Europe, based in Brussels, Belgium, is part of Schering-Plough Corporation (NYSE: SGP) of Kenilworth, N.J., USA.

Schering-Plough is a global science-based health care company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough's vision is to earn the trust of the physicians, patients and customers served by its more than 30,000 people around the world. The company is based in Kenilworth, N.J., USA, and its Web site is http://www.schering-plough.com.

Posted by Ralph at 07:23 PM --- Printer-friendly version | Comments (0)

October 11, 2004

Purified Interferon Successful for Difficult HCV

The following report caught my eye for several reasons. First of all, I am surprised this study was even reported seeing as it is only about one patient. Apparently, the results are still significant.

Secondly, 76 months of treatment is a LONG time (over six years, to be exact). I can't help wondering what this treatment cost and if it would be covered by medical insurance if and when approved.

Third, I was really intrigued with the fact that this form of interferon is apparently closer to that found in nature.

And, finally, the fact that there were no substantial negative effects/side-effects from the therapy. Step by step, inch by inch, we make progress...

Highly Purified Natural Interferon Alfa (Multiferon) Could Be an Alternative Therapy in Difficult-to-treat HCV Patients

A currently 65-year-old patient with histologically proven chronic hepatitis C and chronic hepatitis B (seroconversion in 1990) and additional compensated cirrhosis of the liver (Child A) achieved sustained complete biochemical and viral response following 5 and 14 months respectively of therapy with highly purified natural leukocyte interferon-alfa (3 x 3 MU weekly, nIFN-alfa, Multiferon).

Prior to this treatment, various other therapy approaches including recombinant interferon-alfa-2b (rIFN-alfa-2b) or a combination of natural interferon-beta (nIFN-beta) and interferon-gamma (rIFN-gamma) had been carried out. Unfortunately, these had been unsuccessful.

After a total treatment period of 76 months with nIFN-alfa and a subsequent follow-up period of 30 months, no relapse of chronic hepatitis C occurred.

In conclusion, the authors write, "The patient's tolerance of the treatment was excellent and no substantial drug-related adverse events were observed. nIFN-alfa, which - unlike the recombinant IFN-alfa-2b preparations - is a mixture of various physiologically expressed IFN-alpha subtypes, could possibly be an alternative in the treatment of difficult-to-treat patients with chronic hepatitis C, according to German researchers."

Department of General Internal Medicine, Marienhospital Bottrop gGmbH, Germany.

Reference E Musch and others. Successful application of highly purified natural interferon alpha (multiferon) in a chronic hepatitis C patient resistant to preceding treatment approaches. Hepatogastroenterology 51(59): 1476-1479.

Posted by Ralph at 01:39 PM --- Printer-friendly version | Comments (0)

October 09, 2004

New Blood Test Biopsy Alternative

Blood Tests Provide Alternative to Liver Biopsy

A while back I wrote about a biopsy alternative called Fibrospect.

Here is yet another blood test based alternative that has been used successfully in Europe for a couple of years and is now available in the USA. While biopsies are not considered dangerous, they are not without risk. To have a dependable, non-invasive alternative is valuable.

Your gastro may not have the latest information always available to them so it could be helpful for you to bring this up for discussion if a liver biopsy is recommended.

Blood Tests Provide Alternative to Liver Biopsy for Assessing Status of Liver Disease in HCV Patients

Oneida TheraDiagnostics Ltd has launched two non-invasive blood tests for assessing the extent of liver disease in patients infected with hepatitis C virus (HCV). Developed by hepatologists at the Pitie-Salpetriere Hospital and BioPredictive in France, the two tests are called FibroTest and ActiTest.

The new tests provide easily accessible alternatives to liver biopsy, which is currently used to assess liver fibrosis and necroinflammatory activity in these patients. The tests do not replace the use of liver biopsy, however, which may be the appropriate diagnostic in many cases. Whether to use these new blood tests instead of a liver biopsy should be discussed between each individual patient and his/her primary care physician or liver specialist.

Although liver biopsy has long been considered the gold standard for monitoring the status of HCV and to determine therapy options, it is an invasive procedure that carries some risk of serious complications. The new assays use a combination of six serum biochemical markers, plus age and gender data, in a patented algorithm to determine the degree of liver fibrosis and the level of ongoing necroinflammatory activity.

The tests have been available in parts of Europe for the past two years and have recently been launched in the USA. Each test has been clinically validated in HCV patients to enable quantitative, reproducible assessment of fibrogenic and necrotic activity in the livers of HCV patients.

Oneida TheraDiagnostics Ltd. is a recently established company based in the UK offering molecular diagnostic services for clinical studies with particular emphasis on viral disease.

“Our intention is to establish a world-class portfolio of molecular diagnostics that will facilitate individual patient management and clinical trial studies performed in the UK and Ireland. The tests launched today are very well validated and address one of the major challenges in patients with chronic viral hepatitis. They will be the cornerstone of our viral hepatitis diagnostic service,” said Berwyn Clarke, CEO at Oneida.

FibroTest and ActiTest may be recommended by physicians for use in assessing liver status following a diagnosis of HCV. This provides a baseline determination of liver status before the initiation of HCV therapy and a post-treatment assessment of liver status six months after the completion of therapy.

The tests can also be applied for the non-invasive assessment of liver status in patients at risk of complications from a liver biopsy. The blood sample for the tests can be collected in minutes and results normally returned to the doctor within days.

Source
Oneida TheraDiagnostics. www.oneidathd.co.uk “Validated blood tests provide new alternative to liver biopsy for assessing status of liver disease in hepatitis C patients.” Press Release. October 8, 2004.

Posted by Ralph at 01:35 PM --- Printer-friendly version | Comments (0)

October 05, 2004

Hepatitis Interferon Dosing

More Effective Interferon Dosing For HCV Genotype 1

This new trial result is very revealing. Especially given the fact that 70% of chronic Hepatitis c patients in the USA have genotype 1. Note the success rates (along with the failure rates). Apparently with this "improved" method of dosing they got up to 41%. and the drop out rate was only 19%. Now take a closer look at the rates they compare against. These are for the currently accepted standard dosing.

What happened to the 50% success rate that doctors keep talking about? 29% is much lower than that. And look the drop out rate. This is something that is seldom mentioned. 31% discontinue with current therapy because it is intolerable? Wow! So, only a 41% success rate after 31% drop out. Hmmm...

I'm no mathematician, but the final result for people who started the therapy and actually finished successfully seems like it is reduced by 31% first and THEN it's a 41% success rate of those left. Isn't that actually a much lower success rate than 41%?

If you are genotype 1, like me, it seems like these are very important numbers to be armed with when speaking with your doctor about current medical treatment options.

An Induction Dose of Peginterferon Is a More Effective and Better-tolerated Treatment for Patients with Genotype 1 Than Combination Therapy with High Dose Standard Interferon

In this randomized, controlled, multicenter trial, researchers assessed the effectiveness and safety of an induction dose of peginterferon alfa-2b/ PEG-IFN (Peg-Intron) plus ribavirin for initial treatment of patients with genotype 1 chronic HCV infection.

Three hundred and eleven naïve patients infected with genotype 1 and chronic hepatitis were randomly assigned to 48-week treatment with PEG-IFN once weekly (80–100 μg depending on body weight for 8 weeks, followed by 50 μg for the next 40 weeks), or standard interferon alfa-2b/ IFN (Intron A) 6 million units on alternate days, both in combination with ribavirin (1000–1200 mg/day).

Results

PEG-IFN plus ribavirin significantly increased sustained virological response (SVR) compared with IFN plus ribavirin (41.1 vs. 29.3% respectively, P=0.030). Fewer patients discontinued PEG-IFN than IFN (19 vs. 31%, P=0.010).

By logistic regression, SVR in the PEG-IFN group was independently associated with age less than 50 years, and mild fibrosis at liver biopsy.

Conclusions

Combination therapy with an induction dose of PEG-IFN was a more effective and better-tolerated treatment for treatment-naïve patients with genotype 1 than combination therapy with high dose standard IFN.

In patients aged less than 50 years with mild fibrosis, this schedule achieves a very high rate of SVR.

10-08-04

Reference
S Bruno and others. Peginterferon alfa-2b plus ribavirin for naïve patients with genotype 1 chronic hepatitis C: a randomized controlled trial. Journal of Hepatology 41(3): 474-481. September 2004.

Posted by Ralph at 01:20 PM --- Printer-friendly version | Comments (0)

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