• Gregory T Everson, William J Towner, Mitchell N Davis, David L Wyles, Ronald G Nahass, Paul J Thuluvath, Kyle Etzkorn, Federico Hinestrosa, Myron Tong, Mordechai Rabinovitz, John McNally, Diana M Brainard, Lingling Han, Brian Doehle, John G McHutchison, Timothy Morgan, Raymond T Chung, and Tram T Tran.
• Ann. Intern. Med. 2015 Dec 1; 163 (11): 818-26.

BackgroundEffective, pangenotypic treatments for hepatitis C virus (HCV) infection are needed.ObjectiveTo assess the safety and efficacy of sofosbuvir with velpatasvir in patients infected with HCV genotypes 1 to 6.DesignRandomized, phase 2, open-label study. (ClinicalTrials.gov: NCT01858766).Setting48 U.S. sites.Patients377 treatment-naive noncirrhotic patients. In part A, patients infected with HCV genotypes 1 to 6 were randomly assigned to sofosbuvir, 400 mg, with velpatasvir, 25 or 100 mg, for 12 weeks. In part B, patients with genotype 1 or 2 HCV infection were randomly assigned to sofosbuvir, 400 mg, and velpatasvir, 25 or 100 mg, with or without ribavirin for 8 weeks.MeasurementsSustained virologic response at 12 weeks (SVR12).ResultsIn part A, SVR12 rates were 96% (26 of 27) with velpatasvir, 25 mg, and 100% (28 of 28) with velpatasvir, 100 mg, for genotype 1; 93% (25 of 27) in both groups for genotype 3; and 96% (22 of 23) with velpatasvir, 25 mg, and 95% (21 of 22) with velpatasvir, 100 mg, for genotypes 2, 4, 5, and 6. In part B, for genotype 1, SVR12 rates were 87% (26 of 30) with velpatasvir, 25 mg; 83% (25 of 30) with velpatasvir, 25 mg, plus ribavirin; 90% (26 of 29) with velpatasvir, 100 mg; and 81% (25 of 31) with velpatasvir, 100 mg, plus ribavirin. For genotype 2, SVR12 rates were 77% (20 of 26) with velpatasvir, 25 mg; 88% (22 of 25) with velpatasvir, 25 mg, plus ribavirin; 88% (23 of 26) with velpatasvir, 100 mg; and 88% (23 of 26) with velpatasvir, 100 mg, plus ribavirin. Adverse events included fatigue (21%), headache (20%), and nausea (12%). One patient committed suicide.LimitationThe study was open-label, no inferential statistics were planned, and sample sizes were small.ConclusionTwelve weeks of sofosbuvir, 400 mg, and velpatasvir, 100 mg, was well-tolerated and resulted in high SVR in patients infected with HCV genotypes 1 to 6.Primary Funding SourceGilead Sciences.

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