Results of a 28-day Phase 2a Study with PSI-7977 for the Treatment of Chronic Hepatitis C Infection

Pharmasset Announces Results of a 28-day Phase 2a Study with PSI-7977 for the Treatment of Chronic Hepatitis C Infection

--94% or 93% of patients achieved undetectable HCV RNA levels following 28 days of treatment with PSI-7977 200mg or 400mg QD, respectively, in combination with Pegasys(R) and Copegus(R) --Safety and tolerability across all doses were comparable to placebo administered with Pegasys(R) and Copegus(R) --Conference call scheduled for Tuesday, May 4, 2010 at 8:00 AM ET (US)

PRINCETON, N.J., May 4, 2010 /PRNewswire via COMTEX News Network/ -- Pharmasset, Inc. (Nasdaq: VRUS) announced today the efficacy and preliminary safety results from its 28 day phase 2a study with PSI-7977 dosed once daily (QD) in combination with Pegasys(R) (peginterferon alfa-2a) and Copegus(R) (ribavirin), the current standard of care (SOC) in patients with hepatitis C virus (HCV) genotype 1 who were naïve to antiviral therapy. PSI-7977 is one of Pharmasset's investigational nucleotide analogs.

In this study, PSI-7977 demonstrated potent short term antiviral activity and was generally safe and well tolerated. All patients receiving active PSI-7977 demonstrated continuous and substantial declines in HCV RNA with no viral breakthrough during 28 days of therapy at any dose.

"We are encouraged by the emerging clinical profile of PSI-7977, which was well-tolerated by the patients in this study, and which confirms the consistently high RVR rates of these nucleoside and nucleotide analogs," stated M. Michelle Berrey, M.D., MPH, Chief Medical Officer of Pharmasset.

"Our platform technology continues to generate nucleoside/tide analogs with a high degree of efficacy, high barrier to resistance, and a safety profile that we believe differentiates them from other classes of direct acting antivirals (DAA). We plan to quickly progress PSI-7977 into phase 2b studies starting in the fourth quarter 2010, to generate longer term efficacy and safety data."
Intent-to-Treat (ITT) 28-day RVR data from the trial are summarized as follows:





Mean decrease in HCV RNA Percentage of Patients

Study Arm N (log10 IU/mL) at Day 28 with HCV RNA below LOD

(<15 IU/mL) at Day 28

100mg PSI-7977 QD +

SOC 16 -5.3 88% (14/16)

200mg PSI-7977 QD +

SOC 18 -5.1 94% (17/18)

400mg PSI-7977 QD +

SOC 15 -5.3 93% (14/15)

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Placebo + SOC 14 -2.8 21% (3/14)

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Potent and consistent antiviral activity was demonstrated in this study following 28 days of treatment with PSI-7977 in combination with SOC. Patients receiving PSI-7977 100mg QD with SOC achieved a mean 5.3 log10 IU/mL decrease in HCV RNA and 88% (14 of 16) had HCV RNA levels below the limit of detection (<15 IU/mL), or a Rapid Virologic Response (RVR). Following 28 days with PSI-7977 200mg QD with SOC, patients achieved a mean 5.1 log10 IU/mL decrease in HCV RNA and 94% (17 of 18) achieved an RVR. Following 28 days with PSI-7977 400mg QD with SOC, patients achieved a mean 5.3 log10 IU/mL decrease in HCV RNA and 93% (14 of 15) achieved an RVR. In the control group, following 28 days of treatment with placebo and SOC, patients achieved a mean 2.8 log10 IU/mL decrease in HCV RNA and 21% (3 of 14) achieved an RVR. The baseline HCV RNA for all patients enrolled in the study was approximately 6.5 log10 IU/mL, and was similar across all treatment arms. Patients were stratified by IL28B status to ensure balance across cohorts and no patient was excluded based on their status.

Preliminary Safety Summary
Preliminary safety and tolerability for the 28 day treatment period were similar for PSI-7977 with SOC compared to placebo with SOC. There were no serious adverse events reported during the 28 day treatment period, and no adverse events leading to treatment discontinuation. All adverse events reported were of mild to moderate intensity, of which the majority were mild. A similar proportion of patients in each cohort reported adverse events, with the most common adverse events reported as fatigue, nausea, and arthralgias. The frequency and severity of these adverse events, as well as general body system observations, were similar to clinical experience with the standard of care. There were no dose-related changes in safety laboratory assessments, vital signs or ECGs. A dose-dependent decrease in serum ALT was observed coincident with HCV RNA decline.

Overall, there were no drug-related discontinuations, no serious adverse events, and no dose-related trends in adverse events or laboratory abnormalities as compared to placebo with standard of care.
Full analyses of safety, efficacy, and resistance will be presented at a scientific meeting later in 2010.

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). The CDC has reported that almost three million people in the United States are chronically infected with HCV.