::: HCV News :::

10th September 2007
By Sarah Routledge

Pharmasset has reported preliminary safety and potent antiviral activity with its investigational drug following 14 days of monotherapy in 40 patients chronically infected with hepatitis C virus who had failed prior interferon therapy.

The candidate, R7128, is a prodrug of PSI-6130, an oral cytidine nucleoside analog polymerase inhibitor of HCV that is being developed through Pharmasset's collaboration with Roche. The Phase I multiple ascending dose study of R7128 was designed to evaluate safety, tolerability, pharmacokinetics and preliminary antiviral activity.

R7128 demonstrated potent, dose-dependent antiviral activity across the four patient cohorts receiving 750mg or 1500mg administered either once-daily or twice-daily for 14 days as monotherapy. The greatest mean decrease in HCV RNA from baseline was demonstrated in the patient cohort that received 1,500mg twice-daily, the highest dose of R7128 administered in this study. These patients demonstrated a mean 2.7 log10 IU/mL (>99%) decrease in HCV RNA. There was no evidence of viral rebound in any dose cohort during the 14 days of dosing.

R7128 was generally safe and well tolerated in this Phase I multiple ascending dose study. There were no serious adverse events, no adverse events requiring dose modification, no dose-related gastrointestinal adverse events and no clinically significant changes in vital signs, electrocardiograms, hematologic, renal or other laboratory parameters.

Based on the results of this study, Pharmasset and Roche plan to initiate a 28-day study of R7128 in combination with Pegasys (pegylated interferon) plus Copegus (ribavirin) in treatment-naive patients chronically infected with HCV genotype 1. Patient recruitment for this combination study is expected to begin in late September 2007