Sofosbuvir for previously untreated chronic hepatitis C infection.
BACKGROUND In phase 2 trials, the nucleotide polymerase inhibitor sofosbuvir was effective in previously untreated patients with chronic hepatitis C virus (HCV) genotype 1, 2, or 3 infection. METHODS We conducted two phase 3 studies in previously untreated patients with HCV infection. In a single group, open label study, we administered a 12 week regimen of sofosbuvir plus peginterferon alfa 2a and ribavirin in 327 patients with HCV genotype 1, 4, 5, or 6 (of whom 98% had genotype 1 or 4) In a noninferiority trial, 499 patients with HCV genotype 2 or 3 infection were randomly assigned to receive sofosbuvir plus ribavirin for 12 weeks or peginterferon alfa 2a plus ribavirin for 24 weeks. In the two studies, the primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS In the single group study, a sustained virologic response was reported in 90% of patients (95% confidence interval, 87 to 93) In the noninferiority trial, a sustained response was reported in 67% of patients in both the sofosbuvir ribavirin group and the peginterferon ribavirin group. Response rates in the sofosbuvir ribavirin group were lower among patients with genotype 3 infection than among those with genotype 2 infection (56% vs. 97% Adverse events (including fatigue, headache, nausea, and neutropenia) were less common with sofosbuvir than with peginterferon. CONCLUSIONS In a single group study of sofosbuvir combined with peginterferon ribavirin, patients with predominantly genotype 1 or 4 HCV infection had a rate of sustained virologic response of 90% at 12 weeks. In a noninferiority trial, patients with genotype 2 or 3 infection who received either sofosbuvir or peginterferon with ribavirin had nearly identical rates of response (67% Adverse events were less frequent with sofosbuvir than with peginterferon. (Funded by Gilead Sciences; FISSION and NEUTRINO ClinicalTrials.gov numbers, NCT01497366 and NCT01641640, respectively.
The New England journal of medicine