Efficacy of the Protease Inhibitor BI 201335, Polymerase Inhibitor BI 207127, and Ribavirin in Patients With Chronic HCV Infection
Background & Aims
Therapeutic regimens are being developed for patients with hepatitis C virus (HCV) infection that do not include the combination of peginterferon alfa and ribavirin. We investigated the antiviral effect and safety of BI 201335 (an inhibitor of the NS3/4A protease) and BI 207127 (an inhibitor of the NS5B non-nucleoside polymerase) with ribavirin.
Methods
Thirty-two treatment-naïve patients with chronic HCV genotype 1 infection were randomly assigned to groups that were given 400 mg or 600 mg BI 207127 3 times daily plus 120 mg BI 201335 once daily and 1000 to 1200 mg/day ribavirin for 4 weeks. The primary efficacy end point was virologic response (HCV RNA level <25 IU/mL at week 4). Thirty-two patients received treatment; 31 completed all 4 weeks of assigned combination therapy.
Results
In the group given BI 207127 400 mg 3 times daily, the rates of virologic response were 47%, 67%, and 73% at days 15, 22, and 29; a higher rate of response was observed in patients with genotype-1b compared with genotype-1a infections. In the group given BI 207127 600 mg 3 times daily, the rates of virologic response were 82%, 100%, and 100%, respectively, and did not differ among genotypes. One patient in the group given 400 mg 3 times daily had virologic breakthrough (≥1 log10 rebound in HCV RNA) at day 22. The most frequent adverse events were mild gastrointestinal disorders, rash, and photosensitivity. There were no severe or serious adverse events; no patients discontinued therapy prematurely.
Conclusions
The combination of the protease inhibitor BI 201335, the polymerase inhibitor BI 207127, and ribavirin has rapid and strong activity against HCV genotype-1 and did not cause serious or severe adverse events.
Keywords: Drug, Clinical Trial, Direct-Acting Antivirals, Peginterferon-Free
Abbreviations used in this paper: AE, adverse event, DAA, direct-acting antiviral agent, GT, genotype, LLOD, lower limit of detection, LLOQ, lower limit of quantification, NI, nucleoside polymerase inhibitor, NNI, non-nucleoside inhibitor, PegIFN, peginterferon alfa, RBV, ribavirin, SVR, sustained virologic response
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This article has an accompanying continuing education activity on page e14. Learning Objective: Upon completion of this CME activity, successful learners will be able to explain details on the design and results of the SOUND-C1 clinical trial (BI 201335, BI 207127 and RBV in treatment-naïve patients with chronic HCV GT-1 infection) and assess the potential for this regimen as a future treatment for this patient population.
Conflicts of interest The authors disclose the following: S.Z. is a consultant for Abbott Laboratories, Achillion Pharmaceuticals, Anadys Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, iTherX, Janssen/Tibotec, Merck, Novartis, Pfizer, Pharmasset, Roche/Genentech, Santaris Pharma, and Vertex Pharmaceuticals. T.A. is a consultant for Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, Novartis, and Roche. J.-P.Z. is a consultant for Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Roche, Janssen, and Merck/Schering-Plough. D.L. is a consultant for Boerhinger Ingelheim, Bristol-Myers Squibb, Roche, Janssen, Merck, and Cytheris. B.M. is a consultant for MSD, Roche, Janssen, and Gilead Sciences. M.S. is a consultant for Bristol-Myers Squibb and Roche and a speaker for Bristol-Myers Squibb, Falk, Gilead Sciences, Merck, and Roche. A.L. has participated in trials for Boehringer Ingelheim, Roche, MSD, Janssen, and Falk and has received lecture fees from MSD, Roche, and Falk. S.P. is a consultant for Bristol-Myers Squibb, Boehringer Ingelheim, Tibotec/Janssen-Cilag, Gilead Sciences, Roche, Merck/Schering-Plough, and Abbott Laboratories; is a speaker for GlaxoSmithKline, Bristol-Myers Squibb, Boehringer Ingelheim, Tibotec/Janssen-Cilag, Gilead Sciences, Roche, and Schering-Plough; and has received grants from Bristol-Myers Squibb, Gilead Sciences, Roche, and Merck/Schering-Plough. J.-P.B. is a consultant for Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Novartis, and Roche. F.Z. is a consultant for Janssen, Schering-Plough, and Vertex Pharmaceuticals. M.H. is a consultant for Novartis, MSD, Roche, Jansen, and Gilead Sciences. J.O.S., G.K., G.N., C.H., and W.O.B. are employees of Boehringer Ingelheim. The remaining authors disclose no conflicts.
PII: S0016-5085(11)01248-0
doi:10.1053/j.gastro.2011.08.051
© 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.