Valeant's Viramidine hits safety endpoint, fails to meet efficacy endpoint during phase 3 hepatitis C study

By Angela McDaniels

Seattle, March 21 - Valeant Pharmaceuticals International said that anemia rates were statistically significantly lower in patients treated with Viramidine, the company's drug candidate for the treatment of chronic hepatitis C in treatment-naive patients, than those treated with ribavirin during Viser1, the first of two phase 3 pivotal trials of Viramidine.

Specifically, 5% of patients treated with Viramidine experienced anemia versus 24% of patients treated with ribavirin, according to a company news release. Superiority to ribavirin in incidences of anemia was the study's primary safety endpoint.

Patients treated with Viradmidine did not, however, show a higher sustained viral response rate than patients treated with ribavirin, so the study did not meet its non-inferiority efficacy endpoint.

The company said sustained viral response rates were adversely impacted by the effect of lower dosing on a mg/kg basis in the Viramidine arm and by statistically inconsistent results seen in the rest-of-world region.

The overall intent-to-treat sustained viral response rate for Viramidine was 38% versus 52% for ribavirin. On a per protocol basis, however, the sustained viral response rates for Viramidine in North America and Europe combined were 51% versus 56% for ribavirin, according to the release.

In these same regions, the sustained viral response rates for patients weighing less than or equal to 75 kilograms were 62% for Viramidine versus 60% for ribavirin. In both of these analyses, the Viramidine sustained viral response rates met the non-inferiority criteria, the company said.

Adverse events other than anemia were similar between treatment groups. The most common other adverse events associated with combination therapy included fatigue, headache, insomnia, depression and myalgia.

"The Viser1 trial provided sufficient data to show that Viramidine demonstrates meaningful clinical efficacy and superior safety and allows patients to complete optimal therapy by minimizing the chance of experiencing dose reductions or discontinuations as the result of the toxicity of anemia," Kim D. Lamon, president of research and development and chief scientific officer, said in the release.

"Other analyses of the trial data clearly demonstrate that increasing mg/kg concentrations of Viramidine improve the response rate without a proportionate increase in the incidence of anemia.

"In addition, the inconsistencies coming from rest-of-world sites, which represented approximately 20% of the entire population, are an anomaly that confounds the overall results. Reviews of all investigative sites in these countries are underway."

The company is developing Viramidine (taribavirin hydrochloride), a nucleoside (guanosine) analog prodrug of ribavirin, in oral form, for administration in combination with a pegylated interferon for the treatment of chronic hepatitis C in treatment-naive patients.

The Viser1 trial - Viser stands for VIramidine's Safety and Efficacy vs. Ribavirin - compared a fixed 600 mg dose of Viramidine twice a day to a weight-based 1,000/1,200 mg daily dose of ribavirin, both in combination with peginterferon alfa 2b. The fixed dose of Viramidine averaged roughly 15 mg/kg, based on mean weight for the study population.

The study was conducted in the United States, Canada, Europe, Israel, New Zealand and Australia and enrolled 970 treatment-naive subjects with chronic hepatitis C, according to the release.

Treatment duration was based on genotype, with genotypes 2 and 3 receiving 24 weeks of treatment and genotype non 2, 3 receiving 48 weeks of treatment, each with a post-treatment follow-up period of 24 weeks. The study was also stratified for genotype, weight and viral load.

Valeant is a specialty pharmaceutical company based in Costa Mesa, Calif., that discovers, develops, manufactures and markets a broad range of pharmaceutical products.

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