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
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.
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).
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.
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%), 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%).
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
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.