Hepatitis C Drug Sofosbuvir Meets Primary Endpoint in Phase III Trial
Treatment achieves sustained virologic response (Feb. 19)
Results have been reported from the phase III FUSION trial, which evaluated 12 and 16 weeks of therapy with the nucleotide sofosbuvir (Gilead Sciences) plus ribavirin in treatment-experienced patients with genotype-2 or -3 chronic hepatitis C virus (HCV) infection who failed prior treatment. The study met its primary efficacy endpoint of superiority compared with a predefined historic control, with a sustained virologic response (SVR) rate of 25%.
Fifty percent of patients (50/100) in the 12-week arm and 73% of patients (69/95) in the 16-week arm achieved SVR at 12 weeks (SVR12) (P < 0.001 for both arms).
In the FUSION study, patients with HCV genotype 2 or 3 who failed prior interferon (IFN)-based therapy were randomly assigned to receive either a 12-week (n = 103) or a 16-week (n = 98) course of sofosbuvir 400 mg once daily plus ribavirin (1,000 or 1,200 mg/day). Sixty-three percent of the patients were infected with genotype 3.
In the 12-week arm, SVR12 rates were 86% among genotype-2 patients and 30% among genotype-3 patients. In the 16-week arm, SVR12 rates were 94% among genotype-2 patients and 62% among genotype-3 patients. Thirty-four percent of FUSION participants had compensated cirrhosis at baseline. Among these patients, 31% achieved SVR12 in the 12-week arm, and 66% achieved SVR12 in the 16-week arm. All of the patients in the study became HCV-negative on treatment, and relapse accounted for all virologic failures.
No patients discontinued sofosbuvir or ribavirin because of adverse events. The most common adverse events were fatigue, headache, insomnia, and nausea.
According to the drug’s developer (Gilead), results from four pivotal phase III studies of sofosbuvir — FUSION, POSITRON, FISSION, and NEUTRINO — will support the initial regulatory filing for sofosbuvir as part of oral therapy with ribavirin in genotype-2 and -3 treatment-naïve, treatment-experienced, and IFN-intolerant HCV patients, and for sofosbuvir in combination with ribavirin and pegylated IFN in treatment-naïve patients with genotypes 1, 4, 5, and 6.
Source: Gilead Sciences; February 19, 2013.