Efficacy of Glecaprevir/Pibrentasvir for 8 or 12 Weeks in Patients With Hepatitis C Virus Genotype 2, 4, 5, or 6 Infection Without Cirrhosis.

Abstract

BACKGROUND & AIMS:

Hepatitis C virus (HCV) has high genotypic diversity and global distribution. Agents that are effective against all major HCV genotypes, with shorter treatment duration, are needed to reduce disease burden. Glecaprevir (an NS3/4A protease inhibitor) and pibrentasvir (an NS5A inhibitor) have a high barrier to resistance and synergistic antiviral activity. We evaluated the safety and efficacy of 8 and 12 weeks' treatment with glecaprevir/pibrentasvir in patients with HCV genotype 2, 4, 5, or 6 infection without cirrhosis in 3 separate phase 3 trials.

METHODS:

We performed 2 open label, single-arm studies (SURVEYOR-II, Part 4 and ENDURANCE-4) and a randomized, double-blind, placebo-controlled study (ENDURANCE-2). In the ENDURANCE-2 study, adult patients with untreated or previously treated HCV genotype 2 infection without cirrhosis were randomly assigned (2:1) to groups given once-daily oral glecaprevir/pibrentasvir (n = 202; 300 mg/120 mg) or placebo (n = 100) for 12 weeks. In the SURVEYOR-II, Part 4 and ENDURANCE-4 studies, adult patients with untreated or previously treated patients with HCV genotype 2, genotype 4, genotype 5, or genotype 6 infection, without cirrhosis, were given once-daily oral glecaprevir/pibrentasvir (n = 121 in ENDURANCE-4 and n = 145 in SURVEYOR-II) for 12 or 8 weeks, respectively. In all studies the primary endpoint was sustained virologic response at 12 weeks after treatment (SVR12) in the intention-to-treat population.

RESULTS:

Among patients receiving glecaprevir/pibrentasvir for 8 weeks, rates of SVR12 were 98% (95% CI, 94.1-99.3) in those infected with HCV genotype 2 and 93% (95% CI, 83.6-97.3) in those infected with HCV genotypes 4, 5, or 6. Among patients receiving glecaprevir/pibrentasvir for 12 weeks, rates of SVR12 were 99.5% (95% CI, 98.5-100) in those infected with HCV genotype 2 and 99% (95% CI, 97.6-100) in those infected with HCV genotype 4, 5, or 6. No virologic failures occurred in patients with HCV genotype 4, 5, or 6 infections. The frequency and severity of adverse events in patients receiving glecaprevir/pibrentasvir were similar to those of patients who received placebo.

CONCLUSION:

In 3 Phase 3 studies, 8 weeks' treatment with glecaprevir/pibrentasivr produced an SVR12 in at least 93% of patients with chronic HCV genotype 2, 4, 5, or 6 infection without cirrhosis, with virologic failure in less than 1%. The drug combination had a safety profile comparable to 12 week's treatment with glecaprevir/pibrentasvir. ClinicalTrials.gov numbers: NCT02640482 (ENDURANCE-2), NCT02636595 (ENDURANCE-4), and NCT02243293 (SURVEYOR-II).

• Authors: Tarik Asselah, Kris V Kowdley, Neddie Zadeikis, Stanley Wang, Tarek Hassanein, Yves Horsmans, Massimo Colombo, Filipe Calinas, Humberto Aguilar, Victor de Ledinghen, Parvez S Mantry, Christophe Hezode, Rui Tato Marinho, Kosh Agarwal, Frederik Nevens, Magdy Elkhashab, Jens Kort, Ran Liu, Teresa I Ng, Preethi Krishnan, Chih-Wei Lin, Federico J Mensa
• Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (Clin Gastroenterol Hepatol) Vol. 16 Issue 3 Pg. 417-426 (03 2018) ISSN: 1542-7714 [Electronic] United States
• PMID: 28951228 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chemical References

• Aminoisobutyric Acids
• Antiviral Agents
• Benzimidazoles
• Cyclopropanes
• Lactams, Macrocyclic
• Placebos
• Pyrrolidines
• Quinoxalines
• Sulfonamides
• pibrentasvir
• Proline
• Leucine
• glecaprevir

Topics

• Adult
• Aged
• Aminoisobutyric Acids
• Antiviral Agents (adverse effects, therapeutic use)
• Benzimidazoles (adverse effects, therapeutic use)
• Cyclopropanes
• Double-Blind Method
• Drug-Related Side Effects and Adverse Reactions (epidemiology, pathology)
• Female
• Genotype
• Hepacivirus (classification, genetics)
• Hepatitis C, Chronic (drug therapy, virology)
• Humans
• Lactams, Macrocyclic
• Leucine (analogs & derivatives)
• Male
• Middle Aged
• Placebos (administration & dosage)
• Proline (analogs & derivatives)
• Pyrrolidines
• Quinoxalines (adverse effects, therapeutic use)
• Sulfonamides (adverse effects, therapeutic use)
• Treatment Outcome