Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1

Jia Horng Kao, Ming Lung Yu, Cheng Yuan Peng, Jeong Heo, Chi Jen Chu, Ting Tsung Chang, Youn Jae Lee, Tsung Hui Hu, Ki Tae Yoon, Seung Woon Paik, Young Suk Lim, SangHoon Ahn, Vasily Isakov, Fiona McPhee, Wenhua Hu, Eugene Scott Swenson, Philip D. Yin, Michelle Treitel

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Abstract

Background and Aim: This multinational (Taiwan, South Korea, Russia) phase 3 study evaluated the all-oral, ribavirin-free, fixed-dose combination (DCV-TRIO) of daclatasvir (NS5A inhibitor) 30 mg, asunaprevir (NS3 inhibitor) 200 mg, and beclabuvir (NS5B inhibitor) 75 mg, in patients with chronic hepatitis C virus genotype-1 infection, with or without compensated cirrhosis. Methods: UNITY-4 (NCT02170727) was an open-label, two-cohort study in which 169 patients, treatment-naive (n = 138) or treatment-experienced (n = 31), received twice-daily DCV-TRIO for 12 weeks with 24 weeks of post-treatment follow-up. The primary efficacy end point was sustained virologic response at post-treatment week 12 (SVR12) in treatment-naive patients. Results: Eighty-eight (52%) patients were men, 81 (48%) Taiwanese, 78 (46%) Korean, and 10 (6%) Russian; 23 (14%) had compensated cirrhosis, and 52 (31%) were IL28B (rs1297860) non-CC genotype. Baseline resistance-associated NS5A polymorphisms (L31 and/or Y93) were detected in 25/165 (15%) patients with available genotype-1 sequencing data. SVR12 was achieved by 98.6% (136/138; 95% confidence interval: 94.9–99.8%) of treatment-naive and 100% (31/31; 95% confidence interval: 88.8–100%) of treatment-experienced patients. Both virologic failures were found to be infected with hepatitis C virus genotype-6g; 100% SVR12 was observed for genotype-1a (n = 8) and genotype-1b (n = 157). Two patients experienced serious adverse events. Eight (5%) patients experienced reversible grade 3/4 alanine aminotransferase or aspartate aminotransferase elevations, leading to discontinuation in four (2%); all achieved SVR12. There were no grade 3/4 total bilirubin increases and no deaths. Conclusions: Twelve weeks of DCV-TRIO was well tolerated and provided 100% SVR12 in treatment-naive and treatment-experienced patients with genotype-1 infection, with or without cirrhosis, including those with baseline NS5A-L31 or NS5A-Y93 resistance-associated substitutions.

Original languageEnglish
Pages (from-to)1998-2005
Number of pages8
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume32
Issue number12
DOIs
Publication statusPublished - 2017 Dec 1

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Chronic Hepatitis C
Hepacivirus
Genotype
Galectin 3
Fibrosis
Therapeutics
Confidence Intervals
BMS-790052
asunaprevir
8-cyclohexyl-N-((dimethylamino)sulfonyl)-1,1a,2,12b-tetrahydro-11-methoxy-1a-((3-methyl-3,8-diazabicyclo(3.2.1)oct-8-yl)carbonyl)cycloprop(d)indolo(2,1-a)(2)benzazepine-5-carboxamide
Republic of Korea
Ribavirin
Russia
Aspartate Aminotransferases
Infection
Alanine Transaminase
Taiwan
Bilirubin
Cohort Studies

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Kao, Jia Horng ; Yu, Ming Lung ; Peng, Cheng Yuan ; Heo, Jeong ; Chu, Chi Jen ; Chang, Ting Tsung ; Lee, Youn Jae ; Hu, Tsung Hui ; Yoon, Ki Tae ; Paik, Seung Woon ; Lim, Young Suk ; Ahn, SangHoon ; Isakov, Vasily ; McPhee, Fiona ; Hu, Wenhua ; Scott Swenson, Eugene ; Yin, Philip D. ; Treitel, Michelle. / Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1. In: Journal of Gastroenterology and Hepatology (Australia). 2017 ; Vol. 32, No. 12. pp. 1998-2005.
@article{13ef204d76ff441f885e4a8aa69dbd1a,
title = "Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1",
abstract = "Background and Aim: This multinational (Taiwan, South Korea, Russia) phase 3 study evaluated the all-oral, ribavirin-free, fixed-dose combination (DCV-TRIO) of daclatasvir (NS5A inhibitor) 30 mg, asunaprevir (NS3 inhibitor) 200 mg, and beclabuvir (NS5B inhibitor) 75 mg, in patients with chronic hepatitis C virus genotype-1 infection, with or without compensated cirrhosis. Methods: UNITY-4 (NCT02170727) was an open-label, two-cohort study in which 169 patients, treatment-naive (n = 138) or treatment-experienced (n = 31), received twice-daily DCV-TRIO for 12 weeks with 24 weeks of post-treatment follow-up. The primary efficacy end point was sustained virologic response at post-treatment week 12 (SVR12) in treatment-naive patients. Results: Eighty-eight (52{\%}) patients were men, 81 (48{\%}) Taiwanese, 78 (46{\%}) Korean, and 10 (6{\%}) Russian; 23 (14{\%}) had compensated cirrhosis, and 52 (31{\%}) were IL28B (rs1297860) non-CC genotype. Baseline resistance-associated NS5A polymorphisms (L31 and/or Y93) were detected in 25/165 (15{\%}) patients with available genotype-1 sequencing data. SVR12 was achieved by 98.6{\%} (136/138; 95{\%} confidence interval: 94.9–99.8{\%}) of treatment-naive and 100{\%} (31/31; 95{\%} confidence interval: 88.8–100{\%}) of treatment-experienced patients. Both virologic failures were found to be infected with hepatitis C virus genotype-6g; 100{\%} SVR12 was observed for genotype-1a (n = 8) and genotype-1b (n = 157). Two patients experienced serious adverse events. Eight (5{\%}) patients experienced reversible grade 3/4 alanine aminotransferase or aspartate aminotransferase elevations, leading to discontinuation in four (2{\%}); all achieved SVR12. There were no grade 3/4 total bilirubin increases and no deaths. Conclusions: Twelve weeks of DCV-TRIO was well tolerated and provided 100{\%} SVR12 in treatment-naive and treatment-experienced patients with genotype-1 infection, with or without cirrhosis, including those with baseline NS5A-L31 or NS5A-Y93 resistance-associated substitutions.",
author = "Kao, {Jia Horng} and Yu, {Ming Lung} and Peng, {Cheng Yuan} and Jeong Heo and Chu, {Chi Jen} and Chang, {Ting Tsung} and Lee, {Youn Jae} and Hu, {Tsung Hui} and Yoon, {Ki Tae} and Paik, {Seung Woon} and Lim, {Young Suk} and SangHoon Ahn and Vasily Isakov and Fiona McPhee and Wenhua Hu and {Scott Swenson}, Eugene and Yin, {Philip D.} and Michelle Treitel",
year = "2017",
month = "12",
day = "1",
doi = "10.1111/jgh.13796",
language = "English",
volume = "32",
pages = "1998--2005",
journal = "Journal of Gastroenterology and Hepatology (Australia)",
issn = "0815-9319",
publisher = "Wiley-Blackwell",
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}

Kao, JH, Yu, ML, Peng, CY, Heo, J, Chu, CJ, Chang, TT, Lee, YJ, Hu, TH, Yoon, KT, Paik, SW, Lim, YS, Ahn, S, Isakov, V, McPhee, F, Hu, W, Scott Swenson, E, Yin, PD & Treitel, M 2017, 'Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1', Journal of Gastroenterology and Hepatology (Australia), vol. 32, no. 12, pp. 1998-2005. https://doi.org/10.1111/jgh.13796

Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1. / Kao, Jia Horng; Yu, Ming Lung; Peng, Cheng Yuan; Heo, Jeong; Chu, Chi Jen; Chang, Ting Tsung; Lee, Youn Jae; Hu, Tsung Hui; Yoon, Ki Tae; Paik, Seung Woon; Lim, Young Suk; Ahn, SangHoon; Isakov, Vasily; McPhee, Fiona; Hu, Wenhua; Scott Swenson, Eugene; Yin, Philip D.; Treitel, Michelle.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 32, No. 12, 01.12.2017, p. 1998-2005.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1

AU - Kao, Jia Horng

AU - Yu, Ming Lung

AU - Peng, Cheng Yuan

AU - Heo, Jeong

AU - Chu, Chi Jen

AU - Chang, Ting Tsung

AU - Lee, Youn Jae

AU - Hu, Tsung Hui

AU - Yoon, Ki Tae

AU - Paik, Seung Woon

AU - Lim, Young Suk

AU - Ahn, SangHoon

AU - Isakov, Vasily

AU - McPhee, Fiona

AU - Hu, Wenhua

AU - Scott Swenson, Eugene

AU - Yin, Philip D.

AU - Treitel, Michelle

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Background and Aim: This multinational (Taiwan, South Korea, Russia) phase 3 study evaluated the all-oral, ribavirin-free, fixed-dose combination (DCV-TRIO) of daclatasvir (NS5A inhibitor) 30 mg, asunaprevir (NS3 inhibitor) 200 mg, and beclabuvir (NS5B inhibitor) 75 mg, in patients with chronic hepatitis C virus genotype-1 infection, with or without compensated cirrhosis. Methods: UNITY-4 (NCT02170727) was an open-label, two-cohort study in which 169 patients, treatment-naive (n = 138) or treatment-experienced (n = 31), received twice-daily DCV-TRIO for 12 weeks with 24 weeks of post-treatment follow-up. The primary efficacy end point was sustained virologic response at post-treatment week 12 (SVR12) in treatment-naive patients. Results: Eighty-eight (52%) patients were men, 81 (48%) Taiwanese, 78 (46%) Korean, and 10 (6%) Russian; 23 (14%) had compensated cirrhosis, and 52 (31%) were IL28B (rs1297860) non-CC genotype. Baseline resistance-associated NS5A polymorphisms (L31 and/or Y93) were detected in 25/165 (15%) patients with available genotype-1 sequencing data. SVR12 was achieved by 98.6% (136/138; 95% confidence interval: 94.9–99.8%) of treatment-naive and 100% (31/31; 95% confidence interval: 88.8–100%) of treatment-experienced patients. Both virologic failures were found to be infected with hepatitis C virus genotype-6g; 100% SVR12 was observed for genotype-1a (n = 8) and genotype-1b (n = 157). Two patients experienced serious adverse events. Eight (5%) patients experienced reversible grade 3/4 alanine aminotransferase or aspartate aminotransferase elevations, leading to discontinuation in four (2%); all achieved SVR12. There were no grade 3/4 total bilirubin increases and no deaths. Conclusions: Twelve weeks of DCV-TRIO was well tolerated and provided 100% SVR12 in treatment-naive and treatment-experienced patients with genotype-1 infection, with or without cirrhosis, including those with baseline NS5A-L31 or NS5A-Y93 resistance-associated substitutions.

AB - Background and Aim: This multinational (Taiwan, South Korea, Russia) phase 3 study evaluated the all-oral, ribavirin-free, fixed-dose combination (DCV-TRIO) of daclatasvir (NS5A inhibitor) 30 mg, asunaprevir (NS3 inhibitor) 200 mg, and beclabuvir (NS5B inhibitor) 75 mg, in patients with chronic hepatitis C virus genotype-1 infection, with or without compensated cirrhosis. Methods: UNITY-4 (NCT02170727) was an open-label, two-cohort study in which 169 patients, treatment-naive (n = 138) or treatment-experienced (n = 31), received twice-daily DCV-TRIO for 12 weeks with 24 weeks of post-treatment follow-up. The primary efficacy end point was sustained virologic response at post-treatment week 12 (SVR12) in treatment-naive patients. Results: Eighty-eight (52%) patients were men, 81 (48%) Taiwanese, 78 (46%) Korean, and 10 (6%) Russian; 23 (14%) had compensated cirrhosis, and 52 (31%) were IL28B (rs1297860) non-CC genotype. Baseline resistance-associated NS5A polymorphisms (L31 and/or Y93) were detected in 25/165 (15%) patients with available genotype-1 sequencing data. SVR12 was achieved by 98.6% (136/138; 95% confidence interval: 94.9–99.8%) of treatment-naive and 100% (31/31; 95% confidence interval: 88.8–100%) of treatment-experienced patients. Both virologic failures were found to be infected with hepatitis C virus genotype-6g; 100% SVR12 was observed for genotype-1a (n = 8) and genotype-1b (n = 157). Two patients experienced serious adverse events. Eight (5%) patients experienced reversible grade 3/4 alanine aminotransferase or aspartate aminotransferase elevations, leading to discontinuation in four (2%); all achieved SVR12. There were no grade 3/4 total bilirubin increases and no deaths. Conclusions: Twelve weeks of DCV-TRIO was well tolerated and provided 100% SVR12 in treatment-naive and treatment-experienced patients with genotype-1 infection, with or without cirrhosis, including those with baseline NS5A-L31 or NS5A-Y93 resistance-associated substitutions.

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DO - 10.1111/jgh.13796

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SP - 1998

EP - 2005

JO - Journal of Gastroenterology and Hepatology (Australia)

JF - Journal of Gastroenterology and Hepatology (Australia)

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