High Efficacy of ABT-493 and ABT-530 Treatment in Patients With HCV Genotype 1 or 3 Infection and Compensated Cirrhosis

Gastroenterology. 2016 Oct;151(4):651-659.e1. doi: 10.1053/j.gastro.2016.07.020. Epub 2016 Jul 25.

Abstract

Background & aims: The combination of ABT-493 (NS3/4A protease inhibitor) plus ABT-530 (NS5A inhibitor) has shown high rates of sustained virologic response at post-treatment week 12 (SVR12) in noncirrhotic patients infected with hepatitis C virus (HCV) genotypes (GTs) 1-6. We describe 2 open-label phase 2 studies investigating the efficacy and safety of ABT-493 plus ABT-530 with or without ribavirin (RBV) in GT1- or GT3-infected patients with compensated cirrhosis.

Methods: Patients with GT1 infection received 200 mg ABT-493 plus 120 mg ABT-530 for 12 weeks. Patients with GT3 infection were randomized 1:1 to receive 300 mg ABT-493 plus 120 mg ABT-530 with or without once-daily 800 mg RBV for 12 weeks; treatment-experienced patients who were not treated with RBV received 16 weeks of therapy. Efficacy was measured by SVR12, defined as an HCV-RNA level less than 25 IU/mL. Adverse events and laboratory parameters were evaluated throughout the study.

Results: Twenty-seven patients with GT1 infection and 55 patients with GT3 infection were enrolled. The majority were treatment-naive (84%) and male (65%). In patients with GT1 infection, SVR12 was achieved by 96% (26 of 27; 95% confidence interval [CI], 82-99) of patients, with 1 relapse. Among GT3-infected patients, SVR12 was achieved in 96% (27 of 28; 95% CI, 82-99) of patients in the RBV-free arm (1 relapse), and in 100% (27 of 27; 95% CI, 88-100) in the RBV-containing arm. The most common adverse events were headache, fatigue, and nausea. Laboratory abnormalities were rare; no patient discontinued treatment.

Conclusions: In cirrhotic HCV GT1- or GT3-infected patients, ABT-493 plus ABT-530 with or without RBV achieved SVR12 rates of 96%-100% and was well tolerated. ClinicalTrials.gov identifiers NCT02243280 and NCT02243293.

Keywords: Glecaprevir; Hepatitis C; Pibrentasvir; SURVEYOR.

Publication types

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

MeSH terms

  • Antiviral Agents / administration & dosage*
  • Benzimidazoles / administration & dosage*
  • Drug Therapy, Combination
  • Female
  • Fibrosis / drug therapy*
  • Fibrosis / virology
  • Genotype
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepatitis C / drug therapy*
  • Hepatitis C / virology
  • Humans
  • Male
  • Middle Aged
  • Pyrrolidines / administration & dosage*
  • Quinoxalines / administration & dosage*
  • Ribavirin / administration & dosage
  • Sulfonamides / administration & dosage*
  • Sustained Virologic Response

Substances

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

Associated data

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