Oral treatment of chronic hepatitis C

Valeant Pharmaceuticals today presented 24-week data from Phase 2 clinical trials of Viramidine, a nucleoside (guanosine) analog Valeant is developing in oral form for the treatment of chronic hepatitis C (HCV) in conjunction with a pegylated interferon.

Valeant presented its data at the European Association for the Study of the Liver (EASL) Conference in Berlin, Germany. The Viramidine Phase 2 study consists of 180 treatment-naove subjects with chronic HCV. The on-going study was an open-label, randomized, active control trial, being conducted at multiple centers in the United States and with patients stratified by genotype.

The study consists of four demographically comparable treatment groups: Viramidine 400 mg BID, Viramidine 600 mg BID, Viramidine 800 mg BID and ribavirin 1000/1200 mg daily all in combination with peginterferon alfa-2a. Treatment duration was based on genotype, with genotypes two and three receiving 24 weeks of treatment and genotype one receiving 48 weeks of treatment, each with a post-treatment follow-up period of 24 weeks.

The interim 24-week data shows that Viramidine demonstrates antiviral activity comparable to that of ribavirin, when used in combination with peginterferon alfa-2a in treatment naove patients, but with a lower incidence of anemia. The data demonstrates a sustained reduction in HCV RNA of approximately two-and-a-half log(10) for all three doses of Viramidine, comparable to the ribavirin group in the same study.

The proportion of patients with greater than or equal to 2 log(10) reduction or non-detectable HCV RNA was 83 percent for both Viramidine (800-1600 mg/day) and ribavirin at 24 weeks.

The results also show the percent of patients with non-detectable HCV RNA at 12 weeks and 24 weeks were similar between all treatment groups. There were also fewer patients in the Viramidine groups with anemia (defined as hemoglobin < 10g/dL) when compared with the ribavirin arm (2 percent versus 24 percent; p < 0.001). In the Viramidine 400 mg BID and 600 mg BID dosage groups, defined anemia (hemoglobin < 10g/dL) did not occur, while there were only two occurrences of anemia in the 800 mg BID group. Other adverse events were similar among treatment groups.

Data was presented by Robert Gish, M.D., the lead investigator on the Viramidine Phase 2 study and Medical Director of the Liver Transplant Program at California Pacific Medical Center in San Francisco. A Phase 3 clinical trial of Viramidine compared to ribavirin in combination with pegylated interferon was initiated in the fourth quarter of 2003 and is ongoing. The Phase 3 trial compares the 600 mg BID dose of Viramidine to ribavirin, each in conjunction with pegylated interferon alpha 2b.