Daclatasvir + asunaprevir + beclabuvir ± ribavirin for chronic HCV genotype 1-infected treatment-naive patients

Gregory T. Everson, Karen D. Sims, Paul J. Thuluvath, Eric Lawitz, Tarek Hassanein, Maribel Rodriguez-Torres, Tadesse Desta, Trevor Hawkins, James M. Levin, Federico Hinestrosa, Vinod Rustgi, Howard Schwartz, Zobair Younossi, Lynn Webster, Norman Gitlin, Timothy Eley, Shu Pang Huang, Fiona Mcphee, Dennis M. Grasela, David F. Gardiner

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Background and Aims: This phase-2b study examined the safety and efficacy of an all-oral, interferon-free combination of the NS5A replication complex inhibitor daclatasvir (DCV), the NS3 protease inhibitor asunaprevir (ASV), and the nonnucleoside NS5B polymerase inhibitor beclabuvir (BCV) with or without ribavirin in patients with HCV genotype (GT) 1 infection. Methods: A total of 187 patients received 12weeks of DCV 30mg BID plus ASV 200mg BID and BCV 150mg BID (n=86) or 75mg BID with (n=21) or without (n=80) weight-based ribavirin BID. The primary endpoint was HCV RNA <25 IU/ml at post-treatment week 12 (SVR12). Results: Overall, 90% of patients (169/187) in the combined treatment groups achieved SVR on or after post-treatment week 12. SVR rates were similar across subgroups (by mITT analysis), i.e. patients with cirrhosis (88%, 14/16), HCV GT-1a (90%, 137/155), and IL28B non-CC genotype (90%, 115/128). There were no drug-related serious AEs or grade 4 AEs. The most frequently reported AEs were headache, diarrhoea, fatigue and nausea. Addition of ribavirin to DCV+ASV+BCV was associated with decreased haemoglobin, compared with DCV+ASV+BCV alone. There were six grade 3/4 laboratory abnormalities noted, all unrelated to the study drugs. Viral breakthrough occurred in 2.5-4.8% of patients across groups and appeared unrelated to BCV dose or ribavirin inclusion. Conclusions: Results support phase 3 evaluation of a twice-daily, fixed-dose formulation of this DCV+ASV+BCV regimen with or without ribavirin in HCV GT-1-infected patients.

Original languageEnglish (US)
Pages (from-to)189-197
Number of pages9
JournalLiver International
Volume36
Issue number2
DOIs
StatePublished - Feb 1 2016

Keywords

  • Direct-acting antiviral
  • Drug combination
  • Liver disease
  • Therapy

ASJC Scopus subject areas

  • Hepatology

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    Everson, G. T., Sims, K. D., Thuluvath, P. J., Lawitz, E., Hassanein, T., Rodriguez-Torres, M., Desta, T., Hawkins, T., Levin, J. M., Hinestrosa, F., Rustgi, V., Schwartz, H., Younossi, Z., Webster, L., Gitlin, N., Eley, T., Huang, S. P., Mcphee, F., Grasela, D. M., & Gardiner, D. F. (2016). Daclatasvir + asunaprevir + beclabuvir ± ribavirin for chronic HCV genotype 1-infected treatment-naive patients. Liver International, 36(2), 189-197. https://doi.org/10.1111/liv.12964