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

• Published in: Journal of gastroenterology and hepatology Vol. 32; no. 12; pp. 1998 - 2005
• Main Authors: 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, Sang Hoon, Isakov, Vasily, McPhee, Fiona, Hu, Wenhua, Scott Swenson, Eugene, Yin, Philip D, Treitel, Michelle
• Format: Journal Article
• Language: English
• Published: Australia Wiley Subscription Services, Inc 01-12-2017
• Subjects: Adult; Aged; Aged, 80 and over; Alanine; Alanine transaminase; Asia; Aspartate aminotransferase; Benzazepines - administration & dosage; Bilirubin; Chronic infection; Cirrhosis; Cohort Studies; Confidence intervals; Drug Combinations; Female; Follow-Up Studies; Genotype; Genotype & phenotype; Hepacivirus - genetics; Hepatitis; Hepatitis C; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - virology; Humans; Imidazoles - administration & dosage; Indoles - administration & dosage; Interferon; Isoquinolines - administration & dosage; Liver; Liver cirrhosis; Male; Middle Aged; NS5A; Republic of Korea; Ribavirin; Russia; Sulfonamides - administration & dosage; Taiwan; treatment; Treatment Outcome; Young Adult; treatment; hepatitis; Asia; NS5A
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1111/jgh.13796

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.