Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis

J Hepatol. 2017 Aug;67(2):263-271. doi: 10.1016/j.jhep.2017.03.039. Epub 2017 Apr 13.

Abstract

Background & aims: Hepatitis C virus (HCV) therapy that is highly efficacious, pangenotypic, with a high barrier to resistance and short treatment duration is desirable. The efficacy and safety of 8- and 12-week treatments with glecaprevir (ABT-493; NS3/4A protease inhibitor) and pibrentasvir (ABT-530; NS5A inhibitor) were evaluated in non-cirrhotic patients with chronic HCV genotype 1-6 infection.

Methods: SURVEYOR-I and SURVEYOR-II were phase II, open-label, multicenter, dose-ranging trials including patients with chronic HCV genotype 1-6 infection who were either previously untreated or treated with pegylated interferon plus ribavirin. Patients received once-daily glecaprevir plus pibrentasvir at varying doses with or without ribavirin for 8 or 12weeks. The primary efficacy endpoint was the percentage of patients with a sustained virologic response at post-treatment week 12 (SVR12).

Results: Of the 449 patients who received varying doses of glecaprevir plus pibrentasvir, 25%, 29%, 39%, and 8% had HCV genotype 1, 2, 3, and 4-6 infection, respectively. Twelve-week treatment achieved SVR12 in 97-100%, 96-100%, 83-94%, and 100% in genotypes 1, 2, 3, and 4-6, respectively. Eight-week treatment with 300mg glecaprevir plus 120mg pibrentasvir in genotype 1-, 2-, or 3-infected patients yielded 97-98% SVR12 with no virologic failures. Three (0.7%) patients discontinued treatment due to adverse events; most events were mild (grade 1) in severity. No post-nadir alanine aminotransferase elevations were observed.

Conclusions: Glecaprevir plus pibrentasvir was well tolerated and achieved high sustained virologic response rates in HCV genotypes 1-6-infected patients without cirrhosis following 8- or 12-week treatment durations.

Lay summary: The combination of direct-acting antivirals glecaprevir and pibrentasvir comprise a once-daily, all-oral, pangenotypic treatment for HCV genotype 1-6 infection. This article describes results from two phase II trials investigating a range of doses at treatment durations of 8 or 12weeks in 449 patients without cirrhosis. Efficacy of the optimal dose, as determined by rates of sustained virologic response at post-treatment week 12, ranged from 92%-100%; treatment was well tolerated and significant laboratory abnormalities were rare.

Clinical trial registration: clinicaltrials.gov Identifiers: NCT02243280 and NCT02243293. http://www.clinicaltrials.gov/show/NCT02243280, http://www.clinicaltrials.gov/show/NCT01939197.

Keywords: ABT-493; ABT-530; D-alanine transaminase; Direct-acting antiviral; Genotype; Hepatitis C, chronic; Interferons; Liver cirrhosis; Pangenotypic; SURVEYOR; Sustained virologic response.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Benzimidazoles / administration & dosage*
  • Benzimidazoles / adverse effects
  • Drug Administration Schedule
  • Drug Resistance, Multiple, Viral / genetics
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / drug effects
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Pyrrolidines / administration & dosage*
  • Pyrrolidines / adverse effects
  • Quinoxalines / administration & dosage*
  • Quinoxalines / adverse effects
  • Ribavirin / administration & dosage
  • Ribavirin / adverse effects
  • Sulfonamides / administration & dosage*
  • Sulfonamides / adverse effects
  • Sustained Virologic Response
  • Treatment Failure

Substances

  • ABT-493
  • ABT-530
  • Antiviral Agents
  • Benzimidazoles
  • Pyrrolidines
  • Quinoxalines
  • Sulfonamides
  • Ribavirin

Associated data

  • ClinicalTrials.gov/NCT02243280
  • ClinicalTrials.gov/NCT02243293
  • ClinicalTrials.gov/NCT01939197