Experimental Polymerase Inhibitor HCV-796 is Safe and Effective in Combination with PegIntron or Pegasys

HCV-796 is an experimental inhibitor of hepatitis C virus (HCV) RNA-dependent RNA polymerase that has demonstrated antiviral activity across multiple HCV genotypes when administered as monotherapy or in combination with pegylated interferon alfa-2b (PegIntron).

In a study presented at the 58th Annual Meeting of the American Association for the Study of Liver Diseases in Boston (November 2-6, 2007), researchers evaluated the safety and antiviral efficacy of HCV-796 when administered with either PegIntron or pegylated interferon alfa-2a (Pegasys), the other marketed formulation.

This Phase I randomized, double-blind trial included adult chronic hepatitis C patients who had not previously received treatment. The mean baseline HCV RNA level was 6.4-6.5 log10 in each group; 71% of patients had HCV genotype 1.

In one group, patients were randomly assigned to receive 500 mg oral HCV-796 or placebo every 12 hours for 14 days; in addition, all were assigned to receive 1.5 mcg/kg PegIntron 1 day before starting HCV-796 or placebo (day -1) and on day 7. In the second group, the design was the same except the patients received 180 mcg Pegasys on day -1 and day 7. In each group, 12-16 patients were assigned to receive HCV-796 with 1 type of pegylated interferon.

Results

• For both types of pegylated interferon, combination with HCV-796 reduced plasma HCV RNA levels more than either PegIntron or Pegasys alone.

• At day 14, the mean reduction in HCV RNA for HCV-796 + PegIntron was 3.4 log10 vs 1.6 log10 for PegIntron alone.

• The mean reduction for HCV-796 + Pegasys was 3.7 log10 vs 1.1 log10 for Pegasys alone.

• For both groups, antiviral activity indicated by mean HCV RNA reductions at day 14 differed by genotype:

• Genotype 1: 2.9 log10 for HCV-796 + PegIntron and 3.2 log10 for HCV-796 + Pegasys.

• Non-1 genotypes: 4.4 log10 and 4.7 log10, respectively.

• The combination of HCV-796 with either type of pegylated interferon was generally well tolerated.

• Common adverse events in all groups were those typically associated with interferon, including headache, chills, and myalgia.

Conclusion

"The combination of HCV-796 with either [PegIntron] or [Pegasys] provides similar antiviral activity across multiple HCV genotypes over 14 days of therapy," the researchers concluded. "Results support clinical studies of more long-term administration of HCV-796 with either [pegylated interferon] therapy.

ViroPharma Incorporated, Exton, PA; Wyeth Research, Collegeville, PA; Northwest Kinetics, Tacoma, WA; Center for Clinical Trials Research, University of Florida, Gainesville, FL.

12/07/07

Reference
S Villano, D Raible, D Harper, and others. Phase 1 evaluation of antiviral activity of the non-nucleoside polymerase inhibitor, HCV-796, in combination with different pegylated interferons in treatment-naive patients with chronic HCV. 58th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, MA, November 2-6, 2007. Abstract 1302.