Efficacy of the Combination of Sofosbuvir, Velpatasvir, and the NS3/4A Protease Inhibitor GS-9857 in Treatment-Naive or Previously Treated Patients With Hepatitis C Virus Genotype 1 or 3 Infections

BACKGROUND & AIMS: We performed a phase 2 trial of the efficacy and safety of 4, 6, and 8 weeks of sofosbuvir, given in combination with the NS5A inhibitor velpatasvir and the NS3/4A protease inhibitor GS-9857, in patients with hepatitis C virus (HCV) infection. METHODS: We enrolled 161 treatment-naive or previously treated patients infected with HCV genotypes 1 or 3 with or without compensated cirrhosis at 2 centers in New Zealand, from September 2014 through March 2015. All patients received sofosbuvir (400 mg) and velpatasvir (100 mg) plus GS9857 (100 mg) once daily. The primary efficacy end point was sustained virologic response at 12 weeks after therapy (SVR12). The duration of therapy was determined by baseline patient characteristics: 4 or 6 weeks for treatment-naive patients without cirrhosis, 6 weeks for treatment-naive patients with cirrhosis, and 6 or 8 weeks for treatment-experienced patients with or without cirrhosis. RESULTS: Four weeks of sofosbuvir, velpatasvir, and GS-9857 produced an SVR12 in 4 of 15 (27%) treatment-naive patients with HCV genotype 1 without cirrhosis. Six weeks of this combination produced a SVR12 in 14 of 15 (93%) treatment-naive patients with HCV genotype 1 without cirrhosis, in 13 of 15 (87%) treatment-naive genotype 1 patients with cirrhosis, in 15 of 18 (83%) treatment-naive patients with HCV genotype 3 with cirrhosis, and in 20 of 30 (67%) patients with HCV genotype 1 who had failed an all-oral regimen of 2 or more direct-acting antiviral agents. Eight weeks of the drug combination produced an SVR12 in 17 of 17 (100%) patients with HCV genotype 1, in 19 of 19 (100%) patients with HCV genotype 3 and cirrhosis who had failed pegylated interferon plus ribavirin, in 25 of 28 (89%) patients with HCV genotype 1 who had failed protease inhibitor-based triple therapy, and in 4 of 4 (100%) patients with HCV genotype 3 who had failed an all-oral regimen of >= 2 direct-acting antiviral agents. The most common reported adverse events were headache, nausea, and fatigue. CONCLUSIONS: Eightweeks of treatment with the combination of sofosbuvir, velpatasvir, and GS-9857 produced an SVR12 in most treatment-naive or previously treated patients with HCV genotype 1 or 3 infections, including those with compensated cirrhosis.