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.

• Authors: 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, Sang Hoon Ahn, Vasily Isakov, Fiona McPhee, Wenhua Hu, Eugene Scott Swenson, Philip D Yin, Michelle Treitel
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 32 Issue 12 Pg. 1998-2005 (Dec 2017) ISSN: 1440-1746 [Electronic] Australia
• PMID: 28370350 (Publication Type: Journal Article)
• Copyright: © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Chemical References

• 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
• Benzazepines
• Carbamates
• Drug Combinations
• Imidazoles
• Indoles
• Isoquinolines
• Pyrrolidines
• Sulfonamides
• Valine
• daclatasvir
• asunaprevir

Topics

• Adult
• Aged
• Aged, 80 and over
• Benzazepines (administration & dosage)
• Carbamates
• Cohort Studies
• Drug Combinations
• Female
• Follow-Up Studies
• Genotype
• Hepacivirus (genetics)
• Hepatitis C, Chronic (drug therapy, virology)
• Humans
• Imidazoles (administration & dosage)
• Indoles (administration & dosage)
• Isoquinolines (administration & dosage)
• Male
• Middle Aged
• Pyrrolidines
• Republic of Korea
• Russia
• Sulfonamides (administration & dosage)
• Taiwan
• Treatment Outcome
• Valine (analogs & derivatives)
• Young Adult