Daclatasvir: A NS5A Replication Complex Inhibitor for Hepatitis C Infection

Ann Pharmacother. 2016 Jan;50(1):39-46. doi: 10.1177/1060028015610342. Epub 2015 Oct 20.

Abstract

Objectives: To review the pharmacology, efficacy, and safety of daclatasvir in the treatment of patients with chronic hepatitis C virus (HCV) infection.

Data sources: A literature search through EMBASE and PubMed was conducted (January 1966 to August 2015) using the terms BMS-790052, daclatasvir, and hepatitis C. References from retrieved articles were reviewed for any additional material. Additionally, the new drug application and prescribing information were retrieved.

Study selection/data extraction: The literature search was limited to human studies published in English. Phase 1, 2, and 3 studies describing the pharmacology, pharmacokinetics, efficacy, and safety of daclatasvir for HCV were identified.

Data synthesis: Daclatasvir, a nonstructural 5A protein inhibitor, combined with sofosbuvir, is indicated for adult patients with chronic HCV genotype 3 regardless of treatment or cirrhosis status. The phase III ALLY-3 trial (n = 152) demonstrated that daclatasvir taken once daily with sofosbuvir for 12 weeks was effective at achieving sustained virological response (SVR) rates in treatment-naïve (97%) and treatment-experienced (94%) patients without cirrhosis. Patients with cirrhosis had significantly lower SVR rates (58 and 69%, respectively). The most common adverse drug events associated with daclatasvir and sofosbuvir in ALLY-3 were headache (20%), fatigue (19%), and nausea (12%).

Conclusions: Daclatasvir, when combined with sofosbuvir, is an effective agent to treat HCV genotype 3, with SVR rates above 90% for patients without cirrhosis who are treatment naïve or experienced. SVR rates for treatment-naïve or -experienced patients with cirrhosis are not as robust (58%-69%).

Keywords: BMS-790052; NS5A inhibitor; daclatasvir; hepatitis C.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Carbamates
  • Drug Therapy, Combination
  • Genotype
  • Headache / chemically induced
  • Hepacivirus / genetics
  • Hepatitis C / drug therapy*
  • Hepatitis C, Chronic / drug therapy
  • Humans
  • Imidazoles / adverse effects
  • Imidazoles / therapeutic use*
  • Liver Cirrhosis / drug therapy
  • Nausea / chemically induced
  • Pyrrolidines
  • Sofosbuvir / adverse effects
  • Sofosbuvir / therapeutic use
  • Valine / analogs & derivatives
  • Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

  • Antiviral Agents
  • Carbamates
  • Imidazoles
  • Pyrrolidines
  • Viral Nonstructural Proteins
  • NS-5 protein, hepatitis C virus
  • Valine
  • daclatasvir
  • Sofosbuvir