Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1
Journal
Journal of Gastroenterology and Hepatology (Australia)
Journal Volume
32
Journal Issue
12
Pages
1998-2005
Date Issued
2017
Author(s)
Yu M.-L.
Peng C.-Y.
Heo J.
Chu C.-J.
Chang T.-T.
Lee Y.-J.
Hu T.-H.
Yoon K.T.
Paik S.W.
Lim Y.S.
Ahn S.H.
Isakov V.
McPhee F.
Hu W.
Scott Swenson E.
Yin P.D.
Treitel M.
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. ? 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
Subjects
Asia; hepatitis; NS5A; treatment
SDGs
Other Subjects
alanine aminotransferase; aspartate aminotransferase; asunaprevir plus beclabuvir plus daclatasvir; bilirubin; nonstructural protein 5A; 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; asunaprevir; benzazepine derivative; BMS-790052; imidazole derivative; indole derivative; isoquinoline derivative; sulfonamide; adult; aged; alanine aminotransferase blood level; Article; aspartate aminotransferase blood level; bilirubin blood level; chronic hepatitis C; cohort analysis; compensated liver cirrhosis; controlled study; coughing; diarrhea; drug efficacy; drug tolerability; drug withdrawal; faintness; fatigue; female; genetic polymorphism; headache; Hepatitis C virus genotype 1; human; hypertransaminasemia; major clinical study; male; multicenter study; myalgia; phase 3 clinical trial; priority journal; pruritus; Russian Federation; South Korea; sustained virologic response; Taiwan; treatment outcome; treatment response; upper respiratory tract infection; chronic hepatitis C; drug combination; follow up; genetics; genotype; Hepacivirus; middle aged; very elderly; virology; young adult; Adult; Aged; Aged, 80 and over; Benzazepines; Cohort Studies; Drug Combinations; Female; Follow-Up Studies; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Imidazoles; Indoles; Isoquinolines; Male; Middle Aged; Republic of Korea; Russia; Sulfonamides; Taiwan; Treatment Outcome; Young Adult
Publisher
Blackwell Publishing
Type
journal article