Efficacy and safety of a fixed dose combination tablet of asunaprevir + beclabuvir + daclatasvir for the treatment of Hepatitis C

Expert Opin Pharmacother. 2020 Feb;21(3):261-273. doi: 10.1080/14656566.2019.1697674. Epub 2020 Jan 8.

Abstract

Introduction: Hepatitis C virus (HCV) is estimated to infect approximately 70 million people worldwide. If left untreated, chronic infection can progress to cirrhosis, liver failure or hepatocellular carcinoma. The advent of new direct-acting antivirals (DAA) has revolutionized patients' chances of treatment and viral elimination. Currently, several DAA options are available on the market.Areas covered: This review focuses on the pharmacokinetics, efficacy, tolerability and safety profile of DCV-TRIO, a twice-daily fixed-dose combination of daclatasvir, asunaprevir and beclabuvir approved in Japan for the treatment of genotype 1 HCV infection.Expert opinion: The DCV-TRIO combination achieved good response rates in genotype 1 patients (SVR12 ≥ 95% in naïve subtype 1b), independently from IL28B genotype, cirrhotic status and prior interferon exposure. On the other hand, unsatisfying response rates were reported in DAA-experienced patients and the risk of RAS selection should not be underestimated. Moreover, DCV-TRIO lacks differentiation from its earlier-launched DAA rivals, presents an inconvenient twice-daily dosing schedule and is not recommended in patients with advanced liver and kidney disease. All these drawbacks considerably limit its effective commercial potential. However, it can be a therapeutic option against HCV in tailored approaches according to the needs of different markets across the world.Abbreviations AE: adverse event; ALT: alanine aminotransferase; AST: aspartate aminotransferase; ASV: asunaprevir; AUC: area under the curve; BCRP: Breast Cancer Resistance Protein; BCV: boceprevir; BID: bis in die; CI: confidence intervals; CLcr: creatinine clearance; DAA: direct acting antivirals; DCV: daclatasvir; EC50: Half maximal effective concentration; GT: genotype; HCV: Hepatitis C virus; IFN: Interferon; NHL: non-Hodgkin lymphoma; OATP: Organic anion transporting polypeptides; OR: odds ratio; P-gp: P-glycoprotein; PK: pharmacokinetics; QD: quo die; RAS: resistance-associated substitutions; SVR: sustained virological response; USD: Unites States dollar.

Keywords: BMS-79125; DAA; DCV-TRIO; HCV; Ximency®; interferon-free combinations.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / therapeutic use
  • Benzazepines / administration & dosage*
  • Carbamates
  • Drug Combinations
  • Genotype
  • Hepacivirus / drug effects
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Imidazoles / administration & dosage*
  • Indoles / administration & dosage*
  • Isoquinolines / administration & dosage*
  • Liver Cirrhosis / prevention & control
  • Pyrrolidines
  • Sulfonamides / administration & dosage*
  • Sustained Virologic Response
  • Tablets
  • 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
  • Tablets
  • Valine
  • daclatasvir
  • asunaprevir