PRINCETON, N.J., Dec. 11 /PRNewswire-FirstCall/ — Pharmasset, Inc. announces that interim results of physician-sponsored studies of clevudine for the treatment of chronic hepatitis B virus (HBV) and both preclinical and clinical results of R7128 for the treatment of chronic hepatitis C virus (HCV) will be presented at the Frontiers in Drug Development in Viral Hepatitis (HEP-DART) conference being held in Lahaina, Hawaii from December 9 – 13, 2007. The abstract titles and abbreviated study summaries are described below. The full conference abstracts are currently available for download in PDF format in the “Events & Presentations” section of Pharmasset’s website at http://investor.pharmasset.com/events.cfm . The full scientific presentations will be available for download in PDF format following the conference in the “Product Pipeline” section of Pharmasset’s website at http://www.pharmasset.com/pipeline .
Clevudine was Superior to Lamivudine in the Patients with HBeAg(+) Chronic Hepatitis B. GK Lau, et al.
Abstract Summary: The aim of this study is to compare the efficacy and safety of clevudine versus lamivudine for 48 weeks in chronic hepatitis B (CHB) e-antigen positive (HBeAg(+)) patients in a randomized and blinded manner. Based on the preliminary results from 22 patients (11 clevudine, 11 lamivudine), 48-weeks of dosing with clevudine 30mg showed superior viral suppression to lamivudine 100mg without the emergence of viral breakthrough in HBeAg(+) CHB patients. At week 48, serum HBV DNA levels were below the level of detection (<300 copies/mL) in 82% of patients in the clevudine group and 36% of patients in the lamivudine group. In the lamivudine group, viral breakthrough occurred in 3 patients during weeks 32-48, but no patient had viral breakthrough during the 48 week treatment period in the clevudine group.
Early biochemical and virological response of clevudine therapy in patients with HBV associated liver cirrhosis. KW Chung, et al.
Abstract Summary: This analysis was performed to evaluate the early biochemical and virological response of clevudine in chronic hepatitis B patients with cirrhosis. Data from 13 patients with chronic hepatitis B and cirrhosis were collected. Preliminary results for patients who have been treated for at least 1 month are presented. Clevudine 30 mg administered once daily demonstrated early viral suppression and significant biochemical improvement in patients with liver cirrhosis.
Clevudine monotherapy showed rapid viral and biochemical response in chronic hepatitis B patients with cirrhosis. CH Lee, et al.
Abstract Summary: This analysis was performed to evaluate the efficacy of clevudine in chronic hepatitis B patients with cirrhosis. Data from 23 patients with chronic hepatitis B and cirrhosis were collected. Among them, 5 patients were diagnosed with decompensated liver cirrhosis or hepatocellular carcinoma (HCC). For patients who received clevudine for at least 12 weeks, preliminary data indicated that 20 patients (87%) had HBV DNA less than 1,000 copies/mL and 17 patients (74%) had normal alanine transferase (ALT). Clevudine 30 mg administered once daily demonstrated potent viral suppression and significant biochemical improvement in patients with cirrhosis.
Novel Mechanism of Action of Clevudine Triphosphate: Evidence for Non- competitive Inhibition of Hepatitis B Virus DNA Polymerase. E Murakami, et al.
Abstract Summary: The unique mechanism of action of clevudine was examined using an endogenous HBV polymerase assay. The mode of inhibition for clevudine triphosphate was determined to be non-competitive. Since several active site mutations are known to confer resistance to clevudine in vitro, clevudine triphosphate may be binding at or near the active site of the HBV polymerase without being utilized as a substrate. To the best of our knowledge, this is the first example of a nucleoside analog triphosphate showing non-competitive inhibition.
Potent Antiviral Activity of the Nucleoside HCV Inhibitor, R7128, in Prior IFN Non-Responders. JG McHutchison, et al.
Abstract Summary: R7128 is a prodrug of PSI-6130, a cytidine nucleoside analog polymerase inhibitor, for treatment of HCV. A 14-day monotherapy study demonstrated that R7128, a direct antiviral, can deliver sufficient antiviral potency via monotherapy to suppress HCV below the level of detection (<15 IU/mL) in an interferon failure population. The mean reduction in HCV RNA with the 1500 mg BID dose was -2.7 log10 IU/mL and ranged from -1.2 to -4.2 log10 (below the limit of detection) at Day 15. Twice-daily (BID) administration was superior to once-daily (QD) administration for antiviral suppression. The pharmacokinetic profile following single and multiple doses indicated good exposure to PSI-6130 with no dose-related adverse events or laboratory abnormalities. The lack of virologic rebound also provides early evidence of high genetic barrier for nucleoside inhibitors of NS5B polymerase. The safety and efficacy of this monotherapy study support further development of R7128 in combination with pegylated interferon and ribavirin.
High Genetic Barrier to HCV Resistance Presented by PSI-6130. A Uzgiris, et al.
Abstract Summary: PSI-6130 is the parent molecule of the prodrug R7128, an orally active inhibitor of the hepatitis C virus NS5B polymerase currently in clinical development. Proprietary and public database containing HCV NS5B sequences representing six HCV genotypes were analyzed for the presence of the S282T substitution. S282T results in a small loss in the antiviral activity of PSI-6130 and is not highly polymorphic in the wild-type HCV population. These in vitro data indicate that there is a high genetic barrier to resistance to PSI-6130. Since PSI-6130 is metabolized to two active triphosphate forms, it is enticing to speculate that the two structurally different active metabolites would further increase the genetic barrier of PSI-6130.
Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing and commercializing novel drugs to treat viral infections. Pharmasset’s primary focus is on the development of oral therapeutics for the treatment of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV).
Pharmasset is currently developing three product candidates. Clevudine, for the treatment of chronic HBV infection, is enrolling Phase 3 clinical trials for registration in the Americas and Europe. Clevudine is already approved for HBV in South Korea and marketed by Bukwang Pharmaceuticals in South Korea under the brand name Levovir. R7128, an orally administered treatment for chronic HCV infection, is enrolling a 4-week Phase 1 clinical trial in combination with Pegasys(R) and Copegus(R) through a strategic collaboration with Roche. Racivir, which is being developed for the treatment of HIV in combination with other approved HIV drugs, has completed a Phase 2 clinical trial.
About Hepatitis B
Hepatitis B viruses can cause liver disease leading to significant morbidity and death. HBV can cause either acute or chronic (lifelong) infection. The World Health Organization (WHO) has reported that approximately 350 million people worldwide have chronic HBV infection. According to the Centers for Disease Control and Prevention (CDC), approximately 1.25 million people in the United States are chronically infected with HBV, and the Hepatitis B Foundation reports that 100,000 people will become infected with HBV this year.
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world’s population, are infected with hepatitis C virus (HCV).