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August 26, 2005

Hepatitis A Vaccinations Highly Recommended

If you are a Hepatitis C patient and have not yet been vaccinated against Hepatitis A, you should be as soon as possible. The story below helps to underline this fact.

While Hepatitis A is not normally deadly for most people, when contracted in HCV patients it has a much higher chance of killing them.

Don't delay. There is really no downside risk to getting the vaccination, and you could be risking your life unnecessarily otherwise.

Hepatitis A vaccine not widely used for Hepatitis C patients

25 Aug 2005

A new study examining whether patients with chronic Hepatitis C virus (HCV) were routinely vaccinated against Hepatitis A virus (HAV) found that vaccination rates were low, even though HAV vaccination is recommended for patients with chronic liver disease.

The results of this study appear in the September 2005 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). Published by John Wiley & Sons, Inc., Hepatology is available online via Wiley InterScience at interscience.wiley.com/journal/hepatology.

The HAV vaccine has been available since 1995, yet HAV infection continues to be one of the most preventable illnesses in the United States. It can cause severe liver disease, liver failure, and even death in patients who already have chronic liver disease. HAV vaccination was recommended for these patients by the 1996 Advisory Committee on Immunization Practices and numerous other health agencies, but it is not known to what extent it is being carried out.

Researchers led by Edmund J. Bini, M.D., M.P.H of the New York University School of Medicine identified 1,193 patients from January to December 2000 at the Veterans Affairs New York Harbor Healthcare System in New York who had chronic HCV infection. Follow-up information was collected through June 30, 2002 to determine the number of patients who were tested for HAV and the number who actually received the HAV vaccine. Patients were considered to be vaccinated if they received at least one dose of the vaccine. The study also examined the number of vaccine doses received, the proportion of patients who were susceptible to HAV among those tested (indicated by a negative HAV antibody result), the incidence of HAV infection during follow-up and the number of visits patients made to their primary care provider.

The results showed that 53.6 percent of the 1,193 patients had antibody testing performed, and almost half of these were susceptible to HAV infection. Yet only 94 patients received the HAV vaccine and of these, 45 received only 1 dose. Among the 94 patients who received the vaccine, 88 had been tested for HAV antibody. A total of 3 patients with HCV infection developed acute HAV infection, one of whom died of liver failure. All of them were known to be susceptible to HAV, but none had received the vaccine.

"The low rates of HAV testing and vaccination are striking given the presence of recommendations to vaccinate these individuals against HAV since 1996, the long duration of follow-up, and the high number of visits with their primary care provider," the authors state. "These findings have substantial public health implications and represent missed opportunities for prevention."

The authors speculate that the reasons for the low vaccination rates could include patient refusal (such as a belief that patients weren't at risk for HAV infection, doubts about the vaccine's effectiveness, or misconceptions about side effects), a lack of knowledge on the part of health care providers, a lack of resources, or because of a greater need to address more pressing health issues during medical visits.

The authors conclude: "Public health efforts at raising awareness about HAV vaccination in patients with chronic liver disease should be strongly encouraged. In addition, further studies to evaluate patient and provider barriers to HAV vaccination are needed to prevent future missed opportunities for vaccination."

Article: "Susceptibility to Hepatitis A in Patients with Chronic Liver Disease Due to Hepatitis C Virus Infection: Missed Opportunities for Vaccination," Michael Shim, Inessa Khaykis, James Park, Edmund Bini, Hepatology; September 2005; (DOI: 10.1002/hep.20830).

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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 11, 2005

A Drug Treatment Based on Glutathione

Okay. This story is of most interest to me because of the origin of the compound they are studying. Oxidized glutathione.

As you may already know, I believe taking the nutritional supplement NAC is important for HCV patients. The body turns NAC into glutathione. While I am not suggesting this is the same as what the researchers are working on, it does point to NAC as being in the right ballpark with regard to nutritional supplementation.

Novelos Therapeutics Reports Positive Results From Phase 1/2 Lung Cancer Study

NOV-002 Treated Patients Show Improved Objective Tumor Response and Higher Tolerance of Chemotherapy Versus the Control Group

NEWTON, MA -- (MARKET WIRE) -- 08/08/2005 -- Novelos Therapeutics, Inc. (OTC BB: NVLT), a biotechnology company focusing on oxidized glutathione for use in fighting cancer and hepatitis, today announced positive results from a U.S.-based Phase 1/2 randomized clinical study in non-small cell lung cancer (NSCLC).

Forty-four chemotherapy-naive Stage IIIB/IV NSCLC patients (late-stage lung cancer patients who have not received prior chemotherapy) were randomized to one of three groups for six months of treatment:

Group A: NOV-002, administered intravenously (IV) and intramuscularly, in combination with cytotoxic chemotherapy.

Group B: NOV-002, administered IV and subcutaneously (SC), in combination with cytotoxic chemotherapy.

Group C: Cytotoxic chemotherapy alone was administered to this control group.

Based on the study protocol, the intent-to-treat analysis of the best overall objective tumor response (i.e. complete or partial tumor shrinkage) showed that eleven out of sixteen (69%) NOV-002 treated patients in Group B demonstrated greater than 50% tumor shrinkage versus only five out of fifteen (33%) in the control group (C). This difference was statistically significant (p=0.044 in a stratified analysis). Six out of thirteen (46%) patients in Group A demonstrated an objective response.

Further, NOV-002 treated patients better tolerated cytotoxic chemotherapy as evidenced by their ability to receive more cycles of chemotherapy compared to the control group (C). 100% of patients in Group B and 85% in Group A were able to complete four cycles of chemotherapy, while only 50% of control group patients (C) were able to do so. These differences were statistically significant (p=0.004). In addition, NOV-002 was well tolerated in this patient population, adding to NOV-002's already extensive safety database.

"We are very encouraged by such positive results in a relatively small Phase 1/2 study," said Dr. Christopher Pazoles, Vice President of Research & Development of Novelos Therapeutics. "The study revealed statistically significant improvement in a number of important efficacy measures after treatment with NOV-002 in combination with chemotherapy compared to chemotherapy alone. This was particularly evident in the case of patients receiving NOV-002 both intravenously and subcutaneously."

"Achieving these positive results in a U.S.-based Phase 1/2 clinical study is especially meaningful for us, because they provide confirmation of the clinical efficacy and excellent safety demonstrated in Russia where NOV-002 is already approved and marketed as GLUTOXIM®," added Harry Palmin, President and Acting CEO of Novelos Therapeutics. "We look forward to commencing a Phase 2B/3 NSCLC study next year."

Lung cancer is the leading cause of cancer death in the U.S. Lung cancer is expected to be diagnosed in approximately 175,000 people, and be responsible for about 165,000 deaths in 2005. NSCLC accounts for more than 80% of lung cancer. Only about 15% of NSCLC patients are diagnosed early enough to be eligible for surgery. Platinum-based chemotherapy regimens, such as carboplatin and paclitaxel (Taxol)*, are standard first-line treatment for advanced NSCLC patients, since these patients are not eligible for surgery. One-year survival rate for this first-line therapy is typically only 35%, median survival is 8.5 months and an objective tumor response rate is about 21%. *www.cancer.gov

About Novelos Therapeutics, Inc.

Novelos Therapeutics, Inc. (OTC BB: NVLT) was established in 1996 to commercialize two promising oxidized glutathione-based compounds, NOV-002 and NOV-205, for the treatment of cancer and hepatitis. Both compounds have completed clinical trials in humans and have been approved for use in the Russian Federation where they were developed. NOV-002, marketed in Russia by an unrelated entity under the trade name GLUTOXIM®, has been administered to over 5,000 patients, demonstrating clinical efficacy and excellent safety data. The U.S.-based Phase 1/2 clinical study of NOV-002 for lung cancer has been completed, with positive results. The Company plans to file an IND with the FDA for NOV-205 as a mono-therapy for hepatitis C in 2005.

About the Products

NOV-002, the lead compound, is being developed to treat non-small cell lung cancer (NSCLC). NOV-002 is designed to act as a cytoprotectant and an immunomodulator. When used in combination with chemotherapy, NOV-002 increased the one-year survival rate from 17% to 63% in a Russian study, a result that also represents an 80% improvement above the U.S. 35% current standard of care. A U.S.-based Phase 1/2 clinical study has been completed. NOV-002 treated patients demonstrated improved objective tumor response (defined as greater than 50% tumor shrinkage) and higher tolerance of chemotherapy versus the control group. NOV-002 was well tolerated, thus adding to the compound's already extensive safety data base.

NOV-002 is also being developed to treat refractory (that is, not responsive to chemotherapy) ovarian cancer. Two additional clinical indications, radiation protection and psoriasis, will also be investigated for NOV-002.

NOV-205 is being developed to treat chronic hepatitis C in the U.S. NOV-205 is designed to act as a hepatoprotective agent with immunomodulating and antiviral activity. In Russian clinical studies, when used as mono-therapy for one month in hepatitis B and for two months in hepatitis C, NOV-205 has been shown to greatly reduce or eliminate viral loads and to vastly improve liver function relative to existing drugs on the market.

This news release contains forward-looking statements. Such statements are valid only as of today, and we disclaim any obligation to update this information. These statements are subject to known and unknown risks and uncertainties that may cause actual future experience and results to differ materially from the statements made. These statements are based on our current beliefs and expectations as to such future outcomes. Drug discovery and development involve a high degree of risk. Factors that might cause such a material difference include, among others, uncertainties related to the ability to attract and retain partners for our technologies, the identification of lead compounds, the successful preclinical development thereof, the completion of clinical trials, the FDA review process and other government regulation, our pharmaceutical collaborators' ability to successfully develop and commercialize drug candidates, competition from other pharmaceutical companies, product pricing and third-party reimbursement.

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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.

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August 04, 2005

HCV Treatment and Obesity

This article contains quite a few tidbits of good information (in addition to the primary focus). The description of "signs" that a small number of patients have does a good job of covering possible symptoms and effects of the disease.

It also seems that the main difference in success between Pegasys and Peg-Intron in these patients may have more to do with the difference in dosing between standard levels of medication and weight based dosing.

PEG-Intron Shows Higher Sustained Responses in Obese Patients

by John C. Martin
Article Date: 08-03-05

A small observational study from the Cleveland Clinic is suggesting that the hepatitis C treatment PEG-Intron (peginterferon alfa-2b) helps obese patients with the viral infection achieve sustained therapy responses better than its competitor product, Pegasys (peginterferon alfa-2a).1

The results of the preliminary trial were released at Digestive Disease Week, an annual gastroenterology conference, held this year in Chicago.

Interferon/Ribavirin: The 'Gold Standard'
According to estimates, nearly 4 million Americans are infected with hepatitis C. Three-quarters of this population go on to become chronically infected, and most have accompanying chronic liver disease. HCV accounts for about 15% of acute viral hepatitis, up to 70% of chronic hepatitis cases, and half of all cases of cirrhosis, end-stage liver disease, and liver cancer. The disease is transmitted primarily through contact with blood or blood products, and the "gold standard" treatment at this point includes the combination of a pegylated, or longer-lasting, interferon combined with ribavirin.2

Symptoms of HCV may be absent, but in some cases may include the following:

• Fatigue
• Mild discomfort or tenderness on your upper right side
• Nausea
• Poor appetite
• Muscle and joint pains

A small number of people with the infection develop certain signs, such as skin rashes, kidney disease, neuropathy, cyroglobulins (abnormal blood proteins), rheumatoid factor (an abnormally produced autoantibody that reacts against immunoglobulins in the blood), and low levels of complement (proteins) in the blood.2

PEG-Intron (peginterferon alfa-2b), manufactured by Schering-Plough Pharmaceuticals, is a form of pegylated, or longer-lasting, interferon for hepatitis C. It is prescribed alone or in combination with an oral antiviral medication called ribavirin for adults with the disease. Another pegylated interferon, Pegasys (peginterferon alfa-2a), manufactured by Hoffman-LaRoche Pharmaceuticals, is also combined with ribavirin as a treatment for hepatitis C. Both PEG-Intron and Pegasys, manufactured by Hoffman-LaRoche Pharmaceuticals, are injectable medications used as therapy for hepatitis C.

Sustained Treatment Responses Compared
Doctors in the study compared sustained virologic responses (SVR) in people classified as obese with those considered non-obese using both medications. SVR is defined as continual non-detectable levels of the hepatitis virus for a minimum of six months after therapy ends.3 "Obese patients with hepatitis C virus (HCV) may have more rapid progression of liver disease and lower rates of response to antiviral therapy than nonobese patients," wrote the study's lead investigator, Nizar Zein, MD, in the department of Gastroenterology and Hepatology at the Cleveland Clinic, and his associates.

Thus, the investigators wanted to determine if either Pegasys or PEG-Intron, both combined with the oral antiviral drug, ribavirin, could help their obese patients achieve an SVR.

Study Participant Characteristics
Through a record search, Zein and his group identified nearly 100 patients who had arrived at the Cleveland Clinic between 2001 and 2004 for treatment of their hepatitis C. None of the patients had received treatment prior to their arrival. Each of the patients was infected with genotype 1 HCV, the most common and most difficult to treat strain of the virus.

Thirty-five patients were classified as obese, and the remaining 61 patients were designated non-obese. Each had undergone a biopsy before therapy to determine the health of their livers.

The researchers reported no significant differences in disease characteristics like liver enzyme levels or levels of HCV RNA, the virus' genetic material that doctors look for as an indicator of its presence. Forty percent of the obese patients had steatosis, or fatty liver, compared with just 16 percent of those classified as non-obese. "But frequency of advanced fibrosis or marked inflammation were not significantly different" between the two groups, Zein and his team wrote.

Which Medication Had Better Outcomes?
When analyzing which patients taking Pegasys in combination with ribavirin had achieved an SVR, the researchers found that two of eleven obese patients in this group (18 percent) did so, compared to eight of 29 non-obese patients (28 percent). By contrast, of those in the group taking PEG-Intron combined with ribavirin, nine of 17 obese patients (52 percent) and 14 of 29 non-obese patients (48 percent) similarly achieved a sustained response, the investigators found.

"Mild fibrosis, lower pretreatment HCV RNA, and weight-based dosing were independently associated with attainment of SVR," wrote the study team. In this research, weight-based doses of PEG-Intron were given to the patients compared with standard dosing using Pegasys. That means people taking PEG-Intron are assigned a specific dose based on their individual weight, as opposed to a standard dose that everyone taking Pegasys receives.

"Obese and non-obese patients have equal SVR when treated with weight-based doses of [peginterferon alfa-2b] in combination with ribavirin," wrote Zein and his group in conclusion. "However, when treated with standard-dosed [peginterferon alfa-2a] and ribavirin, obese patients are less likely to attain SVR."

So far, no formal clinical trials have been published comparing the efficacy of PEG-Intron versus Pegasys. However, Schering is sponsoring such a trial whose results will reportedly be released in 2007.

1. Cesario K, Khandwala F, Edwards K, Carey W, Barnes D, Zein N. Impact of obesity on degree of liver disease and response to therapy in patients with chronic hepatitis C genotype 1 infection. Digestive Disease Week 2005. 2005 May 14-19. Chicago, IL.
2. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). National Institutes of Health. Chronic Hepatitis C: Current Disease Management. Available at: http://digestive.niddk.nih.gov/
ddiseases/pubs/chronichepc/index.htm. Accessed July 28, 2005.
3. Fried MW, Shiffman ML, Reddy KR et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002 Sep 26;347(13):975-82.

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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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