Pharmasset announces data from PSI-352938 single ascending dose study

Pharmasset, Inc. (Nasdaq: VRUS) announced today that safety and pharmacokinetic data from the PSI-352938 ("PSI-938") single ascending dose study support progression to a multiple ascending dose trial with PSI-938, which has initiated dosing.  PSI-938 is a guanine nucleotide analog polymerase inhibitor for the treatment of chronic hepatitis C virus (HCV) infection. This study is designed to assess the safety, tolerability and antiviral activity of PSI-938 monotherapy administered over 7 days in HCV-infected individuals.

"PSI-938 is the third differentiated nucleoside analog that Pharmasset has advanced into clinical development for HCV," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "As with RG7128 and PSI-7977, PSI-938 demonstrates a high barrier to resistance in vitro; but unlike the cytidine and uridine analogs, PSI-938 retains equivalent potency against the S282T mutant. As the HCV field moves toward IFN-sparing, all-oral DAA combinations, we continue to believe nucleosides could become the backbone of care given these differentiating attributes and have the potential to be combined with all DAA classes."

PSI-938 Phase 1 Program Overview

The Phase 1 program is investigating the safety, tolerability and pharmacokinetics of PSI-938 in healthy subjects following escalating single doses (Phase 1a), and in patients chronically infected with HCV genotype 1 following repeat dosing for 7 days (Phase 1b).  The Phase 1b study will additionally investigate hepatitis C viral dynamics and monitor for the development of drug resistance.  

Subjects in the Phase 1a single ascending dose study received single doses of PSI-938 ranging from 100 mg to 800 mg or a matching placebo. Preliminary data from the phase 1a single ascending dose study includes:

• No serious adverse events or discontinuations;
• No dose-related adverse events or dose-limiting toxicity;
• No grade III / IV lab abnormalities;
• No clinically significant changes in vital signs or ECGs; and
• PK which supports QD dosing.

A Phase 1b multiple ascending dose trial has now been initiated in treatment-naïve patients with chronic HCV genotype 1 infection. Subjects will be enrolled at multiple centers in the US and randomized to PSI-938 or placebo. Based upon the results from the first time in human study, the first dose of PSI-938 to be tested will be 100 mg administered once daily. The primary objectives of this study are to assess the safety, tolerability, pharmacokinetics and viral dynamics of PSI-938 after repeat dosing over 7 days.

Results from both studies are expected in the third quarter of 2010.