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Gastroenterology. 2014 Feb;146(2):420-9. doi: 10.1053/j.gastro.2013.10.057. Epub 2013 Oct 30.

Efficacy of an interferon- and ribavirin-free regimen of daclatasvir, asunaprevir, and BMS-791325 in treatment-naive patients with HCV genotype 1 infection.

Author information

1
University of Colorado Denver, Aurora, Colorado. Electronic address: greg.everson@ucdenver.edu.
2
Bristol-Myers Squibb, Hopewell, New Jersey.
3
Fundación de Investigación, San Juan, Puerto Rico.
4
Service d'Hépato-Gastroentérologie, CHU Henri Mondor, Créteil, France.
5
The Texas Liver Institute, University of Texas Health Science Center, San Antonio, Texas.
6
Service d'Hépato-Gastroentérologie, Hôpital Saint Joseph, Marseille, France.
7
University Hospital of Limoges, Limoges, France.
8
Metropolitan Research, Arlington, Virginia.
9
Miami Research Associates, South Miami, Florida.
10
Options Health Research, Tulsa, Oklahoma.
11
Hôpital Beaujon, Clichy, France.
12
Université Paris Descartes, INSERM U1610 and Liver Unit, Hôpital Cochin, Paris, France.
13
Mercy Medical Center, Baltimore, Maryland.
14
Bristol-Myers Squibb, Princeton, New Jersey.
15
Bristol-Myers Squibb, Wallingford, Connecticut.

Abstract

BACKGROUND & AIMS:

The combination of peginterferon and ribavirin with telaprevir or boceprevir is the standard treatment of hepatitis C virus (HCV) genotype 1 infection. However, these drugs are not well tolerated because of their side effects and suboptimal virologic responses. In a phase 2a, open-label study, we examined the safety and efficacy of an interferon-free, ribavirin-free regimen of direct-acting antivirals, comprising daclatasvir (an NS5A replication complex inhibitor), asunaprevir (an NS3 protease inhibitor), and BMS-791325 (a non-nucleoside NS5B inhibitor), in patients with chronic HCV infection.

METHODS:

We analyzed data from 66 treatment-naive patients with HCV genotype 1 infection without cirrhosis who were assigned randomly to groups given daclatasvir (60 mg, once daily), asunaprevir (200 mg, twice daily), and BMS-791325 (75 or 150 mg, twice daily) for 12 or 24 weeks. The primary end point was an HCV-RNA level less than 25 IU/mL at 12 weeks after treatment (sustained virologic response at 12 weeks [SVR12]).

RESULTS:

In 64 patients, HCV-RNA levels were less than 25 IU/mL by week 4 of treatment (including 48 of 49 patients with HCV genotype 1a infection and 45 of 46 patients with the non-CC interleukin 28B genotype). Sixty-one patients (92%) achieved SVR12, based on a modified intention-to-treat analysis. Virologic responses were similar between 12 and 24 weeks of treatment. During the study, 2 patients experienced viral breakthrough and 1 patient relapsed. There were no grade 3-4 increases in levels of alanine or aspartate aminotransferases or bilirubin; there were no deaths or discontinuations resulting from serious adverse events or adverse events related to the treatment regimen. The most common adverse events were headache, asthenia, and gastrointestinal symptoms.

CONCLUSIONS:

In a phase 2a study, the all-oral, interferon-free, and ribavirin-free regimen of daclatasvir, asunaprevir, and BMS-791325 was well tolerated and achieved high rates of SVR12 in patients with HCV genotype 1 infection. Further studies of this regimen are warranted. ClinicalTrials.gov, number NCT01455090.

KEYWORDS:

DAA; Drug Combination; EC(50); GT; HCV; IL; Liver Disease; SVR; SVR(24); Therapy; genotype; hepatitis C virus; interleukin; median effective concentration; sustained virologic response; sustained virologic response at 12 weeks

PMID:
24184132
DOI:
10.1053/j.gastro.2013.10.057
[Indexed for MEDLINE]
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