A randomized, placebo-controlled study of the NS5B inhibitor beclabuvir with peginterferon/ribavirin for HCV genotype 1

Summary Beclabuvir is a potent, non‐nucleoside inhibitor of the HCV NS5B RNA polymerase, with nanomolar activity against HCV genotypes 1, 3, 4, 5 and 6 in vitro. This study evaluated the efficacy and safety of beclabuvir, in combination with peginterferon alfa‐2a (pegIFN) and ribavirin (RBV), in HCV...

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Published inJournal of viral hepatitis Vol. 22; no. 8; pp. 658 - 664
Main Authors Tatum, H., Thuluvath, P. J., Lawitz, E., Martorell, C., DeMicco, M., Cohen, S., Rustgi, V., Ravendhran, N., Ghalib, R., Hanson, J., Zamparo, J., Zhao, J., Cooney, E., Treitel, M., Hughes, E.
Format Journal Article
LanguageEnglish
Published England Blackwell Publishing Ltd 01.08.2015
Wiley Subscription Services, Inc
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Summary:Summary Beclabuvir is a potent, non‐nucleoside inhibitor of the HCV NS5B RNA polymerase, with nanomolar activity against HCV genotypes 1, 3, 4, 5 and 6 in vitro. This study evaluated the efficacy and safety of beclabuvir, in combination with peginterferon alfa‐2a (pegIFN) and ribavirin (RBV), in HCV genotype 1. In this randomized (1:1:1), double‐blinded, placebo‐controlled, dose‐ranging phase 2a study, 39 treatment‐naive patients chronically infected with HCV genotype 1 were treated for 48 weeks with beclabuvir (75 mg or 150 mg) plus pegIFN (180 μg) and RBV (1000 mg/day [<75 kg] or 1200 mg/day [≥75 kg]) vs pegIFN/RBV alone. The primary efficacy endpoint of extended rapid virologic response (undetectable HCV RNA at treatment weeks 4 and 12) was achieved by 76.9% (10/13) of patients receiving beclabuvir 75 mg and 38.5% (5/13) receiving beclabuvir 150 mg vs 0% receiving pegIFN/RBV alone. Higher response rates were observed among patients receiving beclabuvir 75 mg for all secondary efficacy endpoints, including sustained virologic response at follow‐up weeks 12 or 24. Three patients experienced virologic breakthrough on treatment, all in the beclabuvir 150‐mg treatment group. Beclabuvir was well tolerated at both doses, with the most commonly observed adverse events (headache, fatigue, nausea, decreased appetite, irritability, depression and insomnia) consistent with those observed with pegIFN/RBV. In conclusion, beclabuvir was both effective and well tolerated when administered in combination with pegIFN/RBV for the treatment of chronic HCV GT 1, supporting the study of beclabuvir as part of an all‐oral regimen for HCV GT1.
Bibliography:Figure S1. Patient disposition.Figure S2. Virologic outcomes, on-treatment observed values.Figure S3. Steady-state (week 12) pharmacokinetics of beclabuvir and its equipotent metabolite BMS-794712.Figure S4. Scatterplots of beclabuvir 24-week composite troughs.Table S1. Demographics and baseline characteristics.
Bristol-Myers Squibb
istex:EBAC801DDE2A7B27A13F0C9F084180CF5863ADED
ArticleID:JVH12372
ark:/67375/WNG-NWXTRSBB-9
ISSN:1352-0504
1365-2893
DOI:10.1111/jvh.12372