title: Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1.
abstract: OBJECTIVE
  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.affiliation: National Taiwan University, Taipei, Taiwan.
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
authors.affiliation: Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ming-Lung
authors.identifier: http://orcid.org/0000-0001-8145-1900
authors.initials: ML
authors.lastname: Yu
authors.affiliation: School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Peng
authors.affiliation: College of Medicine, Pusan National University and Medical Research Institute, Pusan National University Hospital, Busan, Korea.
authors.forename: Jeong
authors.initials: J
authors.lastname: Heo
authors.affiliation: Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chi-Jen
authors.initials: CJ
authors.lastname: Chu
authors.affiliation: National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Ting-Tsung
authors.initials: TT
authors.lastname: Chang
authors.affiliation: Inje University Busan Paik Hospital, Busan, Korea.
authors.forename: Youn-Jae
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung City, Taiwan.
authors.forename: Tsung-Hui
authors.initials: TH
authors.lastname: Hu
authors.affiliation: Pusan National University School of Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea.
authors.forename: Ki Tae
authors.initials: KT
authors.lastname: Yoon
authors.affiliation: Samsung Medical Center, Seoul, Korea.
authors.forename: Seung Woon
authors.initials: SW
authors.lastname: Paik
authors.affiliation: Asan Medical Center, Seoul, Korea.
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Lim
authors.affiliation: Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ahn
authors.affiliation: Institute of Nutrition, Moscow, Russia.
authors.forename: Vasily
authors.initials: V
authors.lastname: Isakov
authors.affiliation: Bristol-Myers Squibb, Princeton, New Jersey, USA.
authors.forename: Fiona
authors.initials: F
authors.lastname: McPhee
authors.affiliation: Bristol-Myers Squibb, Princeton, New Jersey, USA.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Hu
authors.affiliation: Bristol-Myers Squibb, Princeton, New Jersey, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Scott Swenson
authors.affiliation: Bristol-Myers Squibb, Princeton, New Jersey, USA.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Yin
authors.affiliation: Bristol-Myers Squibb, Princeton, New Jersey, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Treitel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001552:Benzazepines / Q000008:administration & dosage*; D002219:Carbamates; D015331:Cohort Studies; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D007211:Indoles / Q000008:administration & dosage*; D007546:Isoquinolines / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D056910:Republic of Korea; D012426:Russia; D013449:Sulfonamides / Q000008:administration & dosage*; D013624:Taiwan; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: C587012:8-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; D001552:Benzazepines; D002219:Carbamates; D004338:Drug Combinations; D007093:Imidazoles; D007211:Indoles; D007546:Isoquinolines; D011759:Pyrrolidines; D013449:Sulfonamides; D014633:Valine; C549273:daclatasvir; C571889:asunaprevir
keywords: Asia; NS5A; hepatitis; treatment