Graham R Foster1, Nezam Afdhal, Stuart K Roberts, Norbert Bräu, Edward J Gane, Stephen Pianko, Eric Lawitz, Alex Thompson, Mitchell L Shiffman, Curtis Cooper, William J Towner, Brian Conway, Peter Ruane, Marc Bourlière, Tarik Asselah, Thomas Berg, Stefan Zeuzem, William Rosenberg, Kosh Agarwal, Catherine A M Stedman, Hongmei Mo, Hadas Dvory-Sobol, Lingling Han, Jing Wang, John McNally, Anu Osinusi, Diana M Brainard, John G McHutchison, Francesco Mazzotta, Tram T Tran, Stuart C Gordon, Keyur Patel, Nancy Reau, Alessandra Mangia, Mark Sulkowski. 1. From Queen Mary University of London (G.R.F.), University College London (W.R.), King's College Hospital (W.R.), and Institute of Liver Studies (K.A.) - all in London; Beth Israel Deaconess Medical Center, Boston (N.A.); Alfred Health and Monash University (S.K.R.) and St. Vincent's Hospital (A.T.), Melbourne, VIC, and Monash Health and Monash University, Clayton, VIC (S.P.) - all in Australia; James J. Peters Veterans Affairs Medical Center, Bronx (N.B.), and Icahn School of Medicine at Mount Sinai, New York (N.B.) - both in New York; Auckland Clinical Studies, Auckland (E.J.G.), and Christchurch Clinical Studies Trust and University of Otago, Christchurch (C.A.M.S.) - both in New Zealand; Texas Liver Institute, University of Texas Health Science Center, San Antonio (E.L.); Liver Institute of Virginia, Richmond (M.L.S.); University of Ottawa, Ottawa (C.C.), and Vancouver Infectious Diseases Centre, Vancouver, BC (B.C.) - both in Canada; Kaiser Permanente (W.J.T.), Ruane Medical (P.R.), and Cedars-Sinai Medical Center (T.T.T.), Los Angeles, and Gilead Sciences, Foster City (H.M., H.D.-S., L.H., J.W., J.M., A.O., D.M.B., J.G.M.) - all in California; Hôpital Saint Joseph, Marseilles (M.B.), and Service d'Hépatologie, Hôpital Beaujon, INSERM UMR 1149, Université Paris Diderot, Clichy (T.A.) - both in France; University Hospital Leipzig, Leipzig (T.B.), and Johann Wolfgang Goethe University, Frankfurt (S.Z.) - both in Germany; Santa Maria Annunziata Hospital, Florence (F.M.), and Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo (A.M.) - both in Italy; Henry Ford Health System, Detroit (S.C.G.); Duke University School of Medicine, Durham, NC (K.P.); Rush University Medical Center, Chicago (N.R.); and Johns Hopkins University, Baltimore (M.S.).
Abstract
BACKGROUND: In phase 2 trials, treatment with the combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir resulted in high rates of sustained virologic response in patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3. METHODS: We conducted two randomized, phase 3, open-label studies involving patients who had received previous treatment for HCV genotype 2 or 3 and those who had not received such treatment, including patients with compensated cirrhosis. In one trial, patients with HCV genotype 2 were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir, in a once-daily, fixed-dose combination tablet (134 patients), or sofosbuvir plus weight-based ribavirin (132 patients) for 12 weeks. In a second trial, patients with HCV genotype 3 were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir for 12 weeks (277 patients) or sofosbuvir-ribavirin for 24 weeks (275 patients). The primary end point for the two trials was a sustained virologic response at 12 weeks after the end of therapy. RESULTS: Among patients with HCV genotype 2, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 99% (95% confidence interval [CI], 96 to 100), which was superior to the rate of 94% (95% CI, 88 to 97) in the sofosbuvir-ribavirin group (P=0.02). Among patients with HCV genotype 3, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 95% (95% CI, 92 to 98), which was superior to the rate of 80% (95% CI, 75 to 85) in the sofosbuvir-ribavirin group (P<0.001). The most common adverse events in the two studies were fatigue, headache, nausea, and insomnia. CONCLUSIONS: Among patients with HCV genotype 2 or 3 with or without previous treatment, including those with compensated cirrhosis, 12 weeks of treatment with sofosbuvir-velpatasvir resulted in rates of sustained virologic response that were superior to those with standard treatment with sofosbuvir-ribavirin. (Funded by Gilead Sciences; ASTRAL-2 ClinicalTrials.gov number, NCT02220998; and ASTRAL-3, NCT02201953.).
BACKGROUND: In phase 2 trials, treatment with the combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir resulted in high rates of sustained virologic response in patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3. METHODS: We conducted two randomized, phase 3, open-label studies involving patients who had received previous treatment for HCV genotype 2 or 3 and those who had not received such treatment, including patients with compensated cirrhosis. In one trial, patients with HCV genotype 2 were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir, in a once-daily, fixed-dose combination tablet (134 patients), or sofosbuvir plus weight-based ribavirin (132 patients) for 12 weeks. In a second trial, patients with HCV genotype 3 were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir for 12 weeks (277 patients) or sofosbuvir-ribavirin for 24 weeks (275 patients). The primary end point for the two trials was a sustained virologic response at 12 weeks after the end of therapy. RESULTS: Among patients with HCV genotype 2, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 99% (95% confidence interval [CI], 96 to 100), which was superior to the rate of 94% (95% CI, 88 to 97) in the sofosbuvir-ribavirin group (P=0.02). Among patients with HCV genotype 3, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 95% (95% CI, 92 to 98), which was superior to the rate of 80% (95% CI, 75 to 85) in the sofosbuvir-ribavirin group (P<0.001). The most common adverse events in the two studies were fatigue, headache, nausea, and insomnia. CONCLUSIONS: Among patients with HCV genotype 2 or 3 with or without previous treatment, including those with compensated cirrhosis, 12 weeks of treatment with sofosbuvir-velpatasvir resulted in rates of sustained virologic response that were superior to those with standard treatment with sofosbuvir-ribavirin. (Funded by Gilead Sciences; ASTRAL-2 ClinicalTrials.gov number, NCT02220998; and ASTRAL-3, NCT02201953.).