Display options
Cite
Everson GT, Sims KD, Thuluvath PJ, et al. Daclatasvir + asunaprevir + beclabuvir ± ribavirin for chronic HCV genotype 1-infected treatment-naive patients. Liver Int. 2015;36(2):189-97doi: 10.1111/liv.12964.
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 : official journal of the International Association for the Study of the Liver, 36(2), 189-97. https://doi.org/10.1111/liv.12964
Everson, Gregory T, et al. "Daclatasvir + asunaprevir + beclabuvir ± ribavirin for chronic HCV genotype 1-infected treatment-naive patients." Liver international : official journal of the International Association for the Study of the Liver vol. 36,2 (2016): 189-97. doi: https://doi.org/10.1111/liv.12964
Everson GT, Sims KD, Thuluvath PJ, Lawitz E, Hassanein T, Rodriguez-Torres M, Desta T, Hawkins T, Levin JM, Hinestrosa F, Rustgi V, Schwartz H, Younossi Z, Webster L, Gitlin N, Eley T, Huang SP, McPhee F, Grasela DM, Gardiner DF. Daclatasvir + asunaprevir + beclabuvir ± ribavirin for chronic HCV genotype 1-infected treatment-naive patients. Liver Int. 2016 Feb;36(2):189-97. doi: 10.1111/liv.12964. Epub 2015 Dec 06. PMID: 26473667.
Copy Download .nbib Format: NLM
Share it on

Liver Int. 2016 Feb;36(2):189-97. doi: 10.1111/liv.12964. Epub 2015 Dec 06.

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

Liver international : official journal of the International Association for the Study of the Liver

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

Affiliations

  1. University of Colorado Denver, Aurora, CO, USA.
  2. Bristol-Myers Squibb, Princeton, NJ, USA.
  3. Mercy Medical Center, Baltimore, MD, USA.
  4. The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, USA.
  5. Southern California GI and Liver Centers, Coronado, CA, USA.
  6. Fundación de Investigación, San Juan, PR, USA.
  7. Precision Research Institute, San Diego, CA, USA.
  8. Southwest CARE Center, Santa Fe, NM, USA.
  9. Dean Foundation for Health, Research and Education Inc, Madison, WI, USA.
  10. Orlando Immunology Center, Orlando, FL, USA.
  11. The Thomas Starzl Transplant Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
  12. Miami Research Associates, South Miami, FL, USA.
  13. Inova Fairfax Hospital, Center for Liver Diseases, Falls Church, VA, USA.
  14. PRA Health Sciences, Raleigh, NC, USA.
  15. Atlanta Gastroenterology Associates' Liver Center, Atlanta, GA, USA.
  16. Bristol-Myers Squibb, Wallingford, CT, USA.

PMID: 26473667 DOI: 10.1111/liv.12964

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 12 weeks of DCV 30 mg BID plus ASV 200 mg BID and BCV 150 mg BID (n = 86) or 75 mg 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.

© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Keywords: direct-acting antiviral; drug combination; liver disease; therapy

Substances

MeSH terms

Publication Types