Idenix Pharmaceuticals has announced results from two Phase IIb studies of the novel combination of valopicitabine and Pegasys in both treatment-naive and treatment-experienced patients infected with the genotype-1 strain of the hepatitis C virus (HCV).

The first study, which was conducted at 23 sites in the U.S., evaluated the safety and efficacy of various doses of valopicitabine plus Pegasys (pegylated interferon alfa-2a) in 173 HCV genotype-1 infected, treatment-naive patients over 48 weeks. The primary endpoint of the study is sustained virologic response (SVR), defined as maintained viral clearance six months after treatment is stopped. At the end of the treatment period, which was 48 weeks, 53 percent of patients treated with 200 mg/day valopicitabine plus pegylated interferon achieved undetectable HCV levels.

Through 48 weeks of treatment, 38 out of a total of 173 patients discontinued the trial due to adverse events (AEs), mostly gastrointestinal (GI). Of these, three patients were receiving the 200 mg/day dose of valopicitabine. Seven serious adverse events (SAEs) were assessed as attributable to either valopicitabine or valopicitabine and pegylated interferon during the first 48 weeks of treatment, most of which were GI- related. In this study, no valopicitabine-related GI SAEs have occurred since March 2006, when the study was amended to reduce the dose of valopicitabine administered to 200 mg/day or 400 mg/day.

The second phase IIb clinical trial, which was conducted at 22 sites in the U.S., evaluated various doses of valopicitabine in combination with pegylated interferon compared with pegylated interferon and ribavirin in 178 HCV genotype-1 infected, treatment-experienced patients for a treatment duration of up to 72 weeks. The primary endpoint of the study was SVR, defined as maintained viral clearance six months after treatment is stopped. The end-of-treatment response rates and post-treatment SVR rates were comparable for patients receiving valopicitabine and pegylated interferon and those receiving pegylated interferon and ribavirin. Of patients treated with valopicitabine in combination with pegylated interferon, none achieved an SVR, compared with one patient retreated with pegylated interferon and ribavirin.

In this study, 31 out of a total of 178 patients discontinued the trial for AEs, of which 12 were GI-related. Seven SAEs were assessed as attributable to either valopicitabine or valopicitabine and pegylated interferon during this study, most of which were GI-related. In this study, no valopicitabine-related GI SAEs occurred after March 2006, when this study was amended to reduce the dose of valopicitabine administered to 400 mg/day.