Anadys Pharmaceuticals Reports Hepatitis C Viral Load Reduction in Completed Phase IB Clinical Trial of Isatoribine

SAN DIEGO -- Anadys Pharmaceuticals, Inc., a biopharmaceutical company committed to the discovery, development and commercialization of novel medicines to treat chronic viral hepatitis and bacterial infections, reported new data from a recently completed multi-component Phase IB clinical trial of isatoribine (ANA245) at the American Association for the Study of Liver Diseases (AASLD) Annual Meeting in Boston.  The isatoribine family of compounds, which includes ANA975, Anadys development candidate for frontline treatment of chronic hepatitis C virus (HCV) infection, is a new class of drugs being developed by Anadys to regulate innate immunity by interacting with Toll-Like Receptor 7.

In a presentation entitled Isatoribine, a Toll-Like Receptor 7 Agonist, Significantly Reduced Plasma Viral Load in a Clinical Proof-of-Concept Study in Patients with Chronic Hepatitis C Virus (HCV) Infection, Yves Horsmans, MD, professor at Cliniques Universitaires St. Luc in Brussels and principal investigator of the study, reported that isatoribine was safe, well tolerated and biologically active in the study.  Although long-term therapeutic utility was not a stated objective of the Phase IB clinical trial and the number of patients was relatively small, results demonstrated a statistically significant viral load reduction in the plasma of patients chronically infected with HCV.

The data from this trial provide the first evidence that a selective agonist of Toll-Like Receptor 7 can reduce circulating levels of HCV by activating innate immunity while avoiding the intense adverse effects often observed with current standard-of-care therapies, said Horsmans.

The Phase IB clinical trial was designed to test the safety and tolerability of isatoribine in patients chronically infected with HCV.  The study was a dose-escalating, open-label evaluation of isatoribine administered intravenously over a period of seven days to 32 adult patients at 200 mg, 400 mg, 600 mg and 800 mg daily doses.  The trial was conducted at two clinical centers in Western Europe.  Patients participating in the study were either HCV-treatment naive or relapsed from interferon-alpha, a component of the current standard of treatment.  Of the 32 patients in the study, 23 were infected with HCV genotype 1, which accounts for more than two-thirds of the infections in the United States yet is the most difficult to treat with current therapies.

Study results showed that isatoribine was biologically active, as evidenced by statistically significant changes in 2-, 5-oligoadenylate synthetase (OAS), a biological marker for the activity of interferon-alpha that is believed to mediate antiviral effects, in patients who received either 600 mg or 800 mg daily for seven days.  The amount of HCV in the bloodstream, or plasma viral load, was most significantly reduced in patients receiving 800 mg daily doses.  After seven days, the average decrease in plasma viral load was 0.76 log10 units, or 82 percent, in these patients. Of the 12 patients in this 800 mg dose group, 10 were infected with HCV genotype 1.  After completing the dosing phase, OAS expression and plasma viral load returned to pre-treatment levels in all patients within seven days.

Isatoribine treatment was safe and well tolerated in the study, with no serious adverse events and a low frequency of mild to moderate side effects, although definitive conclusions regarding product safety cannot be made until the results of future clinical trials of longer duration in more patients are known.  No patient altered treatment or withdrew from the study due to adverse events or clinical laboratory abnormalities.  The results from this completed clinical trial corroborate and extend previously disclosed safety, tolerability, and pharmacokinetic data derived from single doses of isatoribine in healthy volunteers and from other components of the Phase IB clinical trial.

We are very encouraged by the results of this study, which provide the foundation for an upcoming clinical trial of our oral prodrug ANA975 for potential frontline treatment of chronic HCV, said Steve Worland, PhD, Anadys executive vice president, research and development.

About Hepatitis C

Hepatitis C virus, the most common chronic blood-borne infection in the United States, causes inflammation of the liver and may progress to more serious complications such as cirrhosis of the liver, liver cancer and death.  Approximately 2.7 million people in the United States are chronically infected with HCV, and the Centers for Disease Control (CDC) estimates that by the year 2010, the number of deaths attributed annually to HCV could surpass that due to HIV/AIDS.  Worldwide sales for HCV products were an estimated $2.7 billion in 2003, yet current treatments for HCV may be ineffective in up to 50 percent of patients due to the development of drug-resistant viral strains, and many treatments are associated with serious side effects.

Source: Anadys Pharmaceuticals, Inc.

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