Daclatasvir, asunaprevir and beclabuvir fixed-dose combination for patients with genotype 1 chronic hepatitis C

Drugs Today (Barc). 2018 Apr;54(4):237-244. doi: 10.1358/dot.2018.54.4.2795154.

Abstract

Hepatitis C is killing 350,000 persons per year worldwide, 60% of the cases being patients with genotype 1 (GT-1). The fixed-dose tablet combination of daclatasvir (30 mg)/asunaprevir (200 mg)/beclabuvir (75 mg), DCV-TRIO, is one of the latest drugs in the pipeline of interferon-free direct-acting antiviral hepatitis C virus (HCV) therapies. DCV-TRIO increases the genetic barrier to resistance by acting at the same time against three hepatitis C key viral proteins. Results from the UNITY 1, 2, 3 and 4 phase III clinical trials showed that DCV-TRIO exhibited high sustained virologic responses at 12 weeks (between 92% and 100% for HCV GT-1 treatment-naive patients). Furthermore, DCV-TRIO was well tolerated in all studies with reported adverse events (AEs) with an incidence of at least 10% mostly being headache, diarrhea, fatigue and nausea and few AE-related discontinuations. Further research should focus on more real-life data on DCV-TRIO and on developing a pill regimen that works on other HCV genotypes with high genetic barriers and that is available at a reduced cost.

Keywords: Direct-acting antivirals; Inhibitors of NS5A, NS3 and NS5B; Asunaprevir; Beclabuvir; Daclatasvir; Fixed-dose combination; HCV therapy.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Benzazepines / administration & dosage*
  • Benzazepines / adverse effects
  • Carbamates
  • Drug Combinations
  • Drug Resistance, Viral / genetics
  • Genotype
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepacivirus / pathogenicity
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Imidazoles / administration & dosage*
  • Imidazoles / adverse effects
  • Indoles / administration & dosage*
  • Indoles / adverse effects
  • Isoquinolines / administration & dosage*
  • Isoquinolines / adverse effects
  • Pyrrolidines
  • Sulfonamides / administration & dosage*
  • Sulfonamides / adverse effects
  • Sustained Virologic Response
  • Treatment Outcome
  • Valine / analogs & derivatives

Substances

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