Pharmasset Announces R7128 Achieves 85% Rapid Virologic Response in a 4-week Combination Study for the Treatment of Chronic Hepatitis C

85% of patients achieve undetectable HCV RNA levels following 4 weeks of treatment with R7128 1500mg and Pegasys plus Copegus with safety and tolerability comparable to placebo

PRINCETON, N.J., Jan 07, 2008 -- PRNewswire-FirstCall via COMTEX News Network -- Pharmasset, Inc. (Nasdaq: VRUS) announces the preliminary results of a 4-week Phase 1 clinical trial to evaluate two oral dose levels of R7128 in combination with Pegasys (pegylated interferon) plus Copegus (ribavirin) in 50 treatment-naive patients chronically infected with hepatitis C virus (HCV) genotype 1. In this study, R7128 demonstrated potent short-term antiviral activity and was generally safe and well-tolerated. Eighty-five (85%) of patients receiving R7128 1500 mg and Pegasys plus Copegus achieved undetectable HCV RNA levels following 4 weeks of treatment with safety and tolerability comparable to placebo. R7128 is a prodrug of PSI-6130, a cytidine nucleoside analogue polymerase inhibitor of HCV that is being developed through Pharmasset's collaboration with Roche.

Dr. Michelle Berrey, Pharmasset's Chief Medical Officer, stated "R7128, in combination with Pegasys plus Copegus, has shown that nucleoside polymerase inhibitors can demonstrate Rapid Virologic Response (RVR) percentages that are similar to protease inhibitors with an acceptable short-term clinical safety profile. This study also suggests that there appear to be certain synergies between nucleoside polymerase inhibitors and the standard of care that is not found with other classes of HCV inhibitors. The addition of R7128 at both dose levels to the current standard of care has demonstrated a greater percentage of RVR compared to the standard of care alone, which could translate into improved clinical outcomes with longer treatment periods. In addition, the level of antiviral activity from 500mg to 1500mg provides flexibility in selecting doses for future clinical studies."

R7128 Phase 1 Combination Study Overview

The Phase 1 combination clinical trial was a multiple center, observer- blinded, randomized and placebo-controlled study that was conducted in 50 treatment-naive patients chronically infected with HCV genotype 1. The primary objective was to assess the safety, tolerability and pharmacokinetics of R7128 in combination with Pegasys plus Copegus. The secondary objective was to evaluate the change in HCV RNA after 4 weeks of treatment.

The study investigated two oral dose levels of R7128, 500mg and 1500mg, each administered twice-daily (BID) with once-weekly injections of Pegasys plus Copegus. Each cohort of 25 patients was comprised of 20 patients receiving active R7128 and 5 patients receiving placebo with Pegasys plus Copegus (standard of care). The initial evaluation period reported is 4 weeks.

Preliminary Antiviral Activity Summary

Potent antiviral activity was demonstrated following 4 weeks of treatment with R7128 1500mg BID with Pegasys plus Copegus, in which patients achieved a mean 5.12 log10 IU/mL decrease in HCV RNA and 85% (17 of 20) achieved undetectable levels of HCV RNA (<15 IU/mL), or RVR. Following 4 weeks of treatment with R7128 500mg BID with Pegasys plus Copegus, patients achieved a mean 3.82 log10 IU/mL decrease in HCV RNA and 30% (6 of 20) achieved RVR. Following 4 weeks of treatment with placebo with Pegasys plus Copegus, patients achieved a mean 2.95 log10 IU/mL decrease in HCV RNA and 10% (1 of 10) achieved RVR. Baseline HCV RNA was similar across the three treatment groups.

Preliminary Safety Summary

Preliminary safety and tolerability reported were similar for R7128 500mg or R7128 1500mg in combination with Pegasys plus Copegus compared to standard of care alone. There were no serious adverse events reported during the 4 week treatment period. The most common adverse events reported across the treatment groups were headache, chills, fatigue, nausea and fever. Grade 4 neutropenia was observed in 5% (1 of 20) of the patients in each active dosing cohort and in 10% (1 of 10) of the placebo patients. All safety laboratory values and adverse events were within the range expected for the standard of care.
Pharmasset plans to report the final safety and antiviral activity data from the combination study at a scientific meeting in the second calendar quarter of 2008. No additional data or study details will be available until such time.