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J Hepatol. 2015 Jul;63(1):30-7. doi: 10.1016/j.jhep.2015.02.018. Epub 2015 Feb 19.

Daclatasvir and asunaprevir plus peginterferon alfa and ribavirin in HCV genotype 1 or 4 non-responders.

Author information

1
University of Chicago Medical Center, Chicago, IL, USA. Electronic address: djensen110@gmail.com.
2
University of Cincinnati, Cincinnati, OH, USA.
3
Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France.
4
APHP, Université Paris Descartes, INSERM U1016, Paris, France.
5
Johann Wolfgang Goethe Universitaet, Frankfurt, Germany.
6
Hepatology Unit, Hôpital Haut-Leveque, CHU Bordeaux and INSERM U1053, Bordeaux University, France.
7
INSERM U1065, Team 8: Hepatic Complications in Obesity and CHU of Nice Digestive Center, Nice, France.
8
Toronto Liver Center, Toronto, Canada.
9
Gastro One, Germantown, TN, USA.
10
South Denver Gastroenterology, Denver, CO, USA.
11
Center for HIV and Hepatogastroenterology, Duesseldorf, Germany.
12
University of Colorado Denver, Aurora, CO, USA.
13
Virginia Commonwealth University School of Medicine and McGuire Research Institute, McGuire DVAMC, Richmond, VA, USA.
14
Baylor College of Medicine, Houston, TX, USA.
15
Hôpital Saint Antoine, Paris, France.
16
Hepatology Unit, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy.
17
Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.
18
North Shore-Long Island Jewish Health System, Manhasset, NY, USA.
19
Bristol-Myers Squibb Research and Development, Wallingford, CT, USA.
20
Bristol-Myers Squibb Research and Development, Braine-l'Alleud, Belgium.
21
Bristol-Myers Squibb Research and Development, Princeton, NJ, USA.

Abstract

BACKGROUND & AIMS:

Improved therapies for peginterferon/ribavirin null or partial responders are needed. This study evaluated daclatasvir (NS5A inhibitor) and asunaprevir (NS3 protease inhibitor) plus peginterferon alfa-2a and ribavirin in this patient population.

METHODS:

This open-label, phase 3 study (HALLMARK-QUAD; NCT01573351) treated patients with chronic hepatitis C virus (HCV) genotype 1 (n=354) or 4 (n=44) infection who had a prior null or partial response to peginterferon/ribavirin. Patients received daclatasvir 60 mg once-daily plus asunaprevir 100mg twice-daily, with weekly peginterferon alfa-2a and weight-based ribavirin for 24 weeks. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12) among genotype 1-infected patients.

RESULTS:

Daclatasvir plus asunaprevir and peginterferon/ribavirin demonstrated SVR12 rates of 93% (95% CI 90-96) in prior non-responders infected with HCV genotype 1. SVR12 rates among genotype 4-infected patients were 98% (95% CI 93-100); one patient had a missing post-treatment week-12 HCV-RNA measurement, but achieved an SVR at post-treatment week 24, yielding a 100% SVR rate in genotype 4 patients. Prior peginterferon/ribavirin response, sex, age, IL28B genotype, or cirrhosis status did not influence SVR12 rates. Serious adverse events occurred in 6% of patients; 5% discontinued treatment due to an adverse event. Grade 3/4 laboratory abnormalities included neutropenia (22%), lymphopenia (16%), anemia (6%), thrombocytopenia (4%), and ALT/AST elevations (3% each).

CONCLUSIONS:

Daclatasvir plus asunaprevir and peginterferon/ribavirin demonstrated high rates of SVR12 in genotype 1- or 4-infected prior null or partial responders. The combination was well tolerated and no additional safety and tolerability concerns were observed compared with peginterferon/ribavirin regimens.

KEYWORDS:

Asunaprevir; Daclatasvir; Direct-acting antiviral; NS5A; Null; Partial; Peginterferon alfa

PMID:
25703086
DOI:
10.1016/j.jhep.2015.02.018
[Indexed for MEDLINE]

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