High Sustained Virologic Response to Daclatasvir Plus Asunaprevir in Elderly and Cirrhotic Patients with Hepatitis C Virus Genotype 1b Without Baseline NS5A Polymorphisms.

Abstract

INTRODUCTION:

Oral daclatasvir (DCV; pangenotypic NS5A inhibitor) plus asunaprevir (ASV; NS3 protease inhibitor) is approved in Japan and Korea for treatment of chronic hepatitis C virus (HCV) genotype 1. Response to DCV + ASV is affected by DCV resistance-associated polymorphisms (RAPs) in HCV NS5A. The prevalence and influence of these RAPs on 12-week sustained virologic response (SVR12) to DCV + ASV was evaluated in Asian and non-Asian patients.

METHODS:

Data were pooled from 5 national and international studies of patients with HCV genotype 1b (GT-1b) receiving DCV + ASV at their recommended doses. Baseline NS5A RAPs and their effect on SVR12 were assessed overall, in older (≥65 years) patients, patients with cirrhosis, and in patients stratified by baseline HCV RNA or prior treatment experience with interferon-based therapy.

RESULTS:

Baseline NS5A sequences were available from 988 patients (374 Japanese; 125 Korean/Taiwanese; 489 from non-Asian countries), 979 of whom were assessed for SVR12. Pretreatment NS5A-L31F/I/M/V and/or NS5A-Y93H polymorphisms were present in 18% of Japanese and 12-13% of non-Japanese patients; these RAPs reduced SVR12 by 54.9% overall (93.9% [787/838] SVR12 when absent, 39.0% [55/141] SVR12 when present), with comparable reductions observed in Asians and non-Asians and across all categories of treatment experience, age, and cirrhosis. RAP-associated SVR12 rates declined with increasing baseline HCV RNA (SVR12 with RAPs: 64.7% [11/17] at 5-6 log10 IU/mL, 29.8% [14/47] at 7-8 log10). Without baseline RAPs, very high SVR12 rates (92-100%) were observed in older patients and patients with cirrhosis irrespective of national origin, with similarly high rates observed among treatment-naïve and interferon-experienced patients and those with high baseline HCV RNA.

CONCLUSIONS:

Following DCV + ASV treatment, the SVR12 rates in GT-1b patients without baseline NS5A-L31F/I/M/V and/or NS5A-Y93H polymorphisms were very high (approximately 90-100%), irrespective of age, cirrhosis, prior interferon treatment, or baseline HCV RNA.

FUNDING:

Bristol-Myers Squibb.

• Authors: Fiona McPhee, Yoshiyuki Suzuki, Joji Toyota, Yoshiyasu Karino, Kasuaki Chayama, Yoshiiku Kawakami, Min Lung Yu, Sang Hoon Ahn, Hiroki Ishikawa, Rafia Bhore, Nannan Zhou, Dennis Hernandez, Patricia Mendez, Hiromitsu Kumada
• Journal: Advances in therapy (Adv Ther) Vol. 32 Issue 7 Pg. 637-49 (Jul 2015) ISSN: 1865-8652 [Electronic] United States
• PMID: 26155891 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Carbamates
• Imidazoles
• Isoquinolines
• Phosphoproteins
• Pyrrolidines
• Sulfonamides
• Viral Nonstructural Proteins
• nonstructural phosphoprotein 5A, GB virus type C
• Valine
• daclatasvir
• asunaprevir

Topics

• Adult
• Aged
• Antiviral Agents (administration & dosage, therapeutic use)
• Asian People
• Carbamates
• Drug Resistance, Viral (genetics)
• Drug Therapy, Combination
• Genotype
• Hepacivirus (genetics)
• Hepatitis C, Chronic (complications, drug therapy)
• Humans
• Imidazoles (administration & dosage, therapeutic use)
• Isoquinolines (administration & dosage, therapeutic use)
• Japan
• Liver Cirrhosis (drug therapy, etiology)
• Middle Aged
• Phosphoproteins (genetics)
• Polymorphism, Genetic
• Pyrrolidines
• Sulfonamides (administration & dosage, therapeutic use)
• Valine (analogs & derivatives)
• Viral Nonstructural Proteins (genetics)
• Young Adult