BioCentury
ARTICLE | Clinical News

Sofosbuvir: Phase III data

December 23, 2013 8:00 AM UTC

Gilead reported top-line data from 431 evaluable treatment-naive patients with chronic HCV genotype 1 infection in the open-label, international Phase III ION-1 trial evaluating a once-daily, oral fixed-dose combination of 400 mg sofosbuvir plus 90 mg ledipasvir with or without ribavirin for 12 weeks. SVR12 rates were 97.2% for sofosbuvir plus ledipasvir with ribavirin for 12 weeks (n=217) and 97.7% for sofosbuvir plus ledipasvir without ribavirin for 12 weeks (n=214). The trial enrolled 865 patients, including 136 patients with cirrhosis, to receive the fixed-dose combination of sofosbuvir plus ledipasvir with or without ribavirin for 12 or 24 weeks. Data from the 24-week treatment arms are expected next quarter.

In March, Gilead said a DSMB recommended continuation of ION-1 based on a review of safety data from the first 200 patients in all 4 treatment arms and SVR4 data from 100 patients in the 12-week treatment arms. Gilead said the recommendation was based upon SVR4 rates exceeding the predefined threshold of 60% and the absence of significant safety issues (see BioCentury, April 1). Gilead said that prior to the DSMB meeting, the company amended the statistical analysis plan to allow for analysis of the primary endpoint for the two 12-week arms independent of the 24-week arms. Per the amendment, if SVR12 rates in the 12-week arms were >90%, including among patients with cirrhosis, early regulatory applications could be submitted, given that longer treatment durations would not be able to show significantly higher SVR12 rates. Next quarter, Gilead plans to submit an NDA to FDA and an MAA to EMA for the fixed-dose combination of sofosbuvir and ledipasvir to treat chronic HCV genotype 1 infection. The combination product has breakthrough therapy designation in the U.S. ...