All-oral daclatasvir plus asunaprevir for chronic hepatitis C virus (HCV) genotype 1b infection: a sub-analysis in Asian patients from the HALLMARK DUAL study

Jia Horng Kao, Youn Jae Lee, Jeong Heo, SangHoon Ahn, Young Suk Lim, Cheng Yuan Peng, Ting Tsung Chang, Anne Torbeyns, Eric Hughes, Rafia Bhore, Stephanie Noviello

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Abstract

Background & Aims: Daclatasvir plus asunaprevir (DCV + ASV) has demonstrated potent antiviral activity in patients with hepatitis C virus (HCV) genotype 1b (GT-1b) infection in the HALLMARK DUAL trial. This post hoc analysis was conducted to determine the efficacy and safety of this treatment in Asian patients. Methods: Treatment-naive patients were randomly assigned (2:1; double-blinded) to receive DCV (60 mg once daily) plus ASV (100 mg twice daily) or placebo for 12 weeks. Subsequently, placebo patients entered another study, and the remaining patients continued treatment for an additional 12 weeks. Non-responders to peginterferon/ribavirin and ineligible/intolerant patients received dual therapy for 24 weeks. Sustained virological response at post-treatment Week 12 [sustained virological response (SVR)12] and safety outcomes were evaluated. Results: This post hoc analysis included 186 Asian patients (Korean, 78; Taiwanese, 85; others, 23), of whom 32.3% were cirrhotic. SVR12 was observed in 92.3, 78.6 and 80.0% of treatment-naive, ineligible/intolerant and non-responder patients, respectively, and was comparable with non-Asian patients. SVR12 by baseline factors including age, viral load, interleukin-28B genotype and cirrhosis status was similar between the Asian sub-cohorts. Among 18 Asian patients with NS5A-Y93H or NS5A-L31M/V resistance-associated variants (RAVs), seven patients achieved SVR12. Multivariate regression analysis showed a significant influence of NS5A RAVs in both Asian and non-Asian cohorts. The incidence of serious adverse events in Asian patients was low (7.2%). Two Taiwanese patients had elevated alanine aminotransferase (≥5.1 × ULN); both achieved SVR12. Conclusions: All-oral dual therapy with DCV + ASV resulted in high SVR rates and was well tolerated in Asian patients with HCV GT-1b infection.

Original languageEnglish
Pages (from-to)1433-1441
Number of pages9
JournalLiver International
Volume36
Issue number10
DOIs
Publication statusPublished - 2016 Oct 1

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Chronic Hepatitis C
Hepacivirus
Genotype
Infection
BMS-790052
asunaprevir
Therapeutics
Placebos
Safety
Ribavirin
Interleukins
Age Factors
Viral Load
Alanine Transaminase
Antiviral Agents
Fibrosis
Multivariate Analysis

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Kao, Jia Horng ; Lee, Youn Jae ; Heo, Jeong ; Ahn, SangHoon ; Lim, Young Suk ; Peng, Cheng Yuan ; Chang, Ting Tsung ; Torbeyns, Anne ; Hughes, Eric ; Bhore, Rafia ; Noviello, Stephanie. / All-oral daclatasvir plus asunaprevir for chronic hepatitis C virus (HCV) genotype 1b infection : a sub-analysis in Asian patients from the HALLMARK DUAL study. In: Liver International. 2016 ; Vol. 36, No. 10. pp. 1433-1441.
@article{d4c57652c41044c2831ee09dcf86f575,
title = "All-oral daclatasvir plus asunaprevir for chronic hepatitis C virus (HCV) genotype 1b infection: a sub-analysis in Asian patients from the HALLMARK DUAL study",
abstract = "Background & Aims: Daclatasvir plus asunaprevir (DCV + ASV) has demonstrated potent antiviral activity in patients with hepatitis C virus (HCV) genotype 1b (GT-1b) infection in the HALLMARK DUAL trial. This post hoc analysis was conducted to determine the efficacy and safety of this treatment in Asian patients. Methods: Treatment-naive patients were randomly assigned (2:1; double-blinded) to receive DCV (60 mg once daily) plus ASV (100 mg twice daily) or placebo for 12 weeks. Subsequently, placebo patients entered another study, and the remaining patients continued treatment for an additional 12 weeks. Non-responders to peginterferon/ribavirin and ineligible/intolerant patients received dual therapy for 24 weeks. Sustained virological response at post-treatment Week 12 [sustained virological response (SVR)12] and safety outcomes were evaluated. Results: This post hoc analysis included 186 Asian patients (Korean, 78; Taiwanese, 85; others, 23), of whom 32.3{\%} were cirrhotic. SVR12 was observed in 92.3, 78.6 and 80.0{\%} of treatment-naive, ineligible/intolerant and non-responder patients, respectively, and was comparable with non-Asian patients. SVR12 by baseline factors including age, viral load, interleukin-28B genotype and cirrhosis status was similar between the Asian sub-cohorts. Among 18 Asian patients with NS5A-Y93H or NS5A-L31M/V resistance-associated variants (RAVs), seven patients achieved SVR12. Multivariate regression analysis showed a significant influence of NS5A RAVs in both Asian and non-Asian cohorts. The incidence of serious adverse events in Asian patients was low (7.2{\%}). Two Taiwanese patients had elevated alanine aminotransferase (≥5.1 × ULN); both achieved SVR12. Conclusions: All-oral dual therapy with DCV + ASV resulted in high SVR rates and was well tolerated in Asian patients with HCV GT-1b infection.",
author = "Kao, {Jia Horng} and Lee, {Youn Jae} and Jeong Heo and SangHoon Ahn and Lim, {Young Suk} and Peng, {Cheng Yuan} and Chang, {Ting Tsung} and Anne Torbeyns and Eric Hughes and Rafia Bhore and Stephanie Noviello",
year = "2016",
month = "10",
day = "1",
doi = "10.1111/liv.13128",
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pages = "1433--1441",
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Kao, JH, Lee, YJ, Heo, J, Ahn, S, Lim, YS, Peng, CY, Chang, TT, Torbeyns, A, Hughes, E, Bhore, R & Noviello, S 2016, 'All-oral daclatasvir plus asunaprevir for chronic hepatitis C virus (HCV) genotype 1b infection: a sub-analysis in Asian patients from the HALLMARK DUAL study', Liver International, vol. 36, no. 10, pp. 1433-1441. https://doi.org/10.1111/liv.13128

All-oral daclatasvir plus asunaprevir for chronic hepatitis C virus (HCV) genotype 1b infection : a sub-analysis in Asian patients from the HALLMARK DUAL study. / Kao, Jia Horng; Lee, Youn Jae; Heo, Jeong; Ahn, SangHoon; Lim, Young Suk; Peng, Cheng Yuan; Chang, Ting Tsung; Torbeyns, Anne; Hughes, Eric; Bhore, Rafia; Noviello, Stephanie.

In: Liver International, Vol. 36, No. 10, 01.10.2016, p. 1433-1441.

Research output: Contribution to journalArticle

TY - JOUR

T1 - All-oral daclatasvir plus asunaprevir for chronic hepatitis C virus (HCV) genotype 1b infection

T2 - a sub-analysis in Asian patients from the HALLMARK DUAL study

AU - Kao, Jia Horng

AU - Lee, Youn Jae

AU - Heo, Jeong

AU - Ahn, SangHoon

AU - Lim, Young Suk

AU - Peng, Cheng Yuan

AU - Chang, Ting Tsung

AU - Torbeyns, Anne

AU - Hughes, Eric

AU - Bhore, Rafia

AU - Noviello, Stephanie

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Background & Aims: Daclatasvir plus asunaprevir (DCV + ASV) has demonstrated potent antiviral activity in patients with hepatitis C virus (HCV) genotype 1b (GT-1b) infection in the HALLMARK DUAL trial. This post hoc analysis was conducted to determine the efficacy and safety of this treatment in Asian patients. Methods: Treatment-naive patients were randomly assigned (2:1; double-blinded) to receive DCV (60 mg once daily) plus ASV (100 mg twice daily) or placebo for 12 weeks. Subsequently, placebo patients entered another study, and the remaining patients continued treatment for an additional 12 weeks. Non-responders to peginterferon/ribavirin and ineligible/intolerant patients received dual therapy for 24 weeks. Sustained virological response at post-treatment Week 12 [sustained virological response (SVR)12] and safety outcomes were evaluated. Results: This post hoc analysis included 186 Asian patients (Korean, 78; Taiwanese, 85; others, 23), of whom 32.3% were cirrhotic. SVR12 was observed in 92.3, 78.6 and 80.0% of treatment-naive, ineligible/intolerant and non-responder patients, respectively, and was comparable with non-Asian patients. SVR12 by baseline factors including age, viral load, interleukin-28B genotype and cirrhosis status was similar between the Asian sub-cohorts. Among 18 Asian patients with NS5A-Y93H or NS5A-L31M/V resistance-associated variants (RAVs), seven patients achieved SVR12. Multivariate regression analysis showed a significant influence of NS5A RAVs in both Asian and non-Asian cohorts. The incidence of serious adverse events in Asian patients was low (7.2%). Two Taiwanese patients had elevated alanine aminotransferase (≥5.1 × ULN); both achieved SVR12. Conclusions: All-oral dual therapy with DCV + ASV resulted in high SVR rates and was well tolerated in Asian patients with HCV GT-1b infection.

AB - Background & Aims: Daclatasvir plus asunaprevir (DCV + ASV) has demonstrated potent antiviral activity in patients with hepatitis C virus (HCV) genotype 1b (GT-1b) infection in the HALLMARK DUAL trial. This post hoc analysis was conducted to determine the efficacy and safety of this treatment in Asian patients. Methods: Treatment-naive patients were randomly assigned (2:1; double-blinded) to receive DCV (60 mg once daily) plus ASV (100 mg twice daily) or placebo for 12 weeks. Subsequently, placebo patients entered another study, and the remaining patients continued treatment for an additional 12 weeks. Non-responders to peginterferon/ribavirin and ineligible/intolerant patients received dual therapy for 24 weeks. Sustained virological response at post-treatment Week 12 [sustained virological response (SVR)12] and safety outcomes were evaluated. Results: This post hoc analysis included 186 Asian patients (Korean, 78; Taiwanese, 85; others, 23), of whom 32.3% were cirrhotic. SVR12 was observed in 92.3, 78.6 and 80.0% of treatment-naive, ineligible/intolerant and non-responder patients, respectively, and was comparable with non-Asian patients. SVR12 by baseline factors including age, viral load, interleukin-28B genotype and cirrhosis status was similar between the Asian sub-cohorts. Among 18 Asian patients with NS5A-Y93H or NS5A-L31M/V resistance-associated variants (RAVs), seven patients achieved SVR12. Multivariate regression analysis showed a significant influence of NS5A RAVs in both Asian and non-Asian cohorts. The incidence of serious adverse events in Asian patients was low (7.2%). Two Taiwanese patients had elevated alanine aminotransferase (≥5.1 × ULN); both achieved SVR12. Conclusions: All-oral dual therapy with DCV + ASV resulted in high SVR rates and was well tolerated in Asian patients with HCV GT-1b infection.

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