• Maribel Rodriguez-Torres, Eric Lawitz, Kris V Kowdley, David R Nelson, Edwin Dejesus, John G McHutchison, Melanie T Cornpropst, Michael Mader, Efsevia Albanis, Deyuan Jiang, Christy M Hebner, William T Symonds, Michelle M Berrey, and Jay Lalezari.
• Fundacion de Investigacion, San Juan, Puerto Rico. mrodrigueztorres@fdipr.com
• J. Hepatol. 2013 Apr 1; 58 (4): 663-8.

Background & AimsSofosbuvir (formerly GS-7977) is a pyrimidine nucleotide analog inhibitor of the hepatitis C virus (HCV) NS5B polymerase. We assessed the safety, tolerability, antiviral activity, and pharmacokinetics of sofosbuvir plus pegylated-interferon (PegIFN)/ribavirin (RBV) in a 28-day, dose-ranging trial in treatment-naïve patients infected with genotype 1 HCV.MethodsIn this double-blind study, 64 patients were randomized (1:1:1:1) to receive one of three once-daily doses of oral sofosbuvir (100, 200, or 400mg) or placebo plus PegIFN/RBV for 28 days, after which all patients continued to receive PegIFN/RBV alone for a further 44 weeks.ResultsPatients in the sofosbuvir/PegIFN/RBV groups experienced mean reductions in HCV RNA >5 log₁₀ IU/ml (-5.3 for 100 mg, -5.1 for 200 mg and -5.3 for 400 mg) vs. -2.8 log₁₀ IU/ml for placebo/PegIFN/RBV after 28 days. Rapid virologic response (RVR) rates were markedly higher after sofosbuvir treatment (88-94%) than placebo (21%), as were rates of sustained virologic response (SVR) at post-treatment Week 24 (56%, 83%, and 80% for sofosbuvir 100, 200, and 400 mg, respectively, vs. 43% for placebo). The number of patients experiencing virologic breakthrough and post-treatment relapse was higher in the sofosbuvir 100 mg group than sofosbuvir 200 and 400 mg groups. Sofosbuvir was well tolerated; the most frequent adverse events were fatigue and nausea.ConclusionsThese results support further studies with sofosbuvir at 200 mg and 400 mg to determine the optimal dose and treatment duration of sofosbuvir in HCV genotype 1.Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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