Article first published online: 30 JAN 2012
Copyright © 2011 American Association for the Study of Liver Diseases
Volume 55, Issue 3, pages 742–748, March 2012
How to Cite
Chayama, K., Takahashi, S., Toyota, J., Karino, Y., Ikeda, K., Ishikawa, H., Watanabe, H., McPhee, F., Hughes, E. and Kumada, H. (2012), Dual therapy with the nonstructural protein 5A inhibitor, daclatasvir, and the nonstructural protein 3 protease inhibitor, asunaprevir, in hepatitis C virus genotype 1b–infected null responders. Hepatology, 55: 742–748. doi: 10.1002/hep.24724
Potential conflict of interest: Nothing to report.
This study was funded by Bristol-Myers Squibb. Editorial assistance for the preparation of the manuscript for this article was provided by Richard Boehme, Ph.D., of Articulate Science and was funded by Bristol-Myers Squibb.
This article first published online ahead of print on 30 January 2012. The following corrections have since been made: “BMS“790052” has been replaced throughout with “daclatasvir”; “BMS-50032” has been replaced throughout with “asunaprevir”. The article has been updated online and in print.
- Issue published online: 23 FEB 2012
- Article first published online: 30 JAN 2012
- Accepted manuscript online: 10 OCT 2011 11:05AM EST
- Manuscript Accepted: 27 SEP 2011
- Manuscript Received: 22 JUL 2011
Patients with chronic hepatitis C virus (HCV) infection and previous null response to pegylated interferon (Peg-IFN) and ribavirin (RBV) have limited therapeutic options. HCV genotype 1 is the most common worldwide and the most difficult to treat; genotype 1b is the most common subtype of genotype 1 outside North America. The enhanced antiviral activity achieved by combining two direct-acting antiviral (DAA) agents may improve clinical outcomes. This open-label, phase IIa study included 10 patients with chronic HCV genotype 1b infection and previous null response (<2 log10 reduction in HCV RNA after 12 weeks) to Peg-IFN and RBV. Patients received dual DAA treatment for 24 weeks with the nonstructural protein 5A replication complex inhibitor, daclatasvir (60 mg once-daily), and the nonstructural protein 3 protease inhibitor, asunaprevir (initially 600 mg twice-daily, then subsequently reduced to 200 mg twice-daily). The primary efficacy endpoint was the proportion of patients with sustained virologic response (SVR) at 12 weeks post-treatment (SVR12). Nine patients completed 24 weeks of treatment; 1 patient discontinued treatment after 2 weeks. In the 9 patients who completed the full course of treatment, HCV RNA was undetectable at week 8 and remained undetectable through the end of treatment; all 9 patients achieved SVR12 and SVR24. HCV RNA also remained undetectable post-treatment in the patient who discontinued after 2 weeks. There was no viral breakthrough. Diarrhea and headache, generally mild, were the most common adverse events; transaminase elevations were reported in 3 patients, but did not result in discontinuation. Conclusions: Dual therapy with daclatasvir and asunaprevir, without Peg-IFN and RBV, can achieve high SVR rates in difficult-to-treat patients with HCV genotype 1b infection and previous null response to Peg-IFN and RBV. (HEPATOLOGY 2011)