Eight Weeks of Treatment With Glecaprevir/Pibrentasvir Is Safe and Efficacious in an Integrated Analysis of Treatment-Naïve Patients With Hepatitis C Virus Infection.

Abstract

BACKGROUND & AIMS:

The direct-acting antiviral combination glecaprevir/pibrentasvir has been approved by the Food and Drug Administration for 8 weeks of treatment in treatment-naïve patients with hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis. We performed an integrated analysis of data from trials to evaluate the overall efficacy and safety of 8 weeks of glecaprevir/pibrentasvir in treatment-naïve patients without cirrhosis or with compensated cirrhosis.

METHODS:

We pooled data from 8 phase 2 or phase 3 trials of treatment-naïve patients with HCV genotype 1 to 6 infections, without cirrhosis or with compensated cirrhosis, who received 8 weeks of glecaprevir/pibrentasvir.

RESULTS:

Of 1248 patients, 343 (27%) had cirrhosis. Most patients were white (80%) and had HCV genotype 1 infection (47%) or genotype 3 infection (22%); the median age was 54 years. Overall rates of sustained virologic response at post-treatment week 12 were 97.6% (1218 of 1248) in the intention to treat (ITT) and 99.3% (1218 of 1226) in the modified ITT populations. When we excluded patients with genotype 3 infections with compensated cirrhosis (consistent with the European label), rates of sustained virologic response at post-treatment week 12 were 97.6% in the ITT and 99.4% in the modified ITT populations. Eight virologic failures (7 in patients without cirrhosis and 1 in a patient with cirrhosis) occurred in the ITT population. Virologic failure was not associated with markers of advanced liver disease or populations of interest (current alcohol use, opioid substitution therapy, history of injection-drug use, and severe renal impairment). Treatment-emergent adverse events (AEs) occurred in 58% of patients. The most frequent AEs (>10%) were headache (12%) and fatigue (12%). Serious AEs and AEs that led to glecaprevir/pibrentasvir discontinuation were reported in 2% and less than 1% of patients, respectively.

CONCLUSIONS:

In a pooled analysis of data from 8 trials, we found that 8 weeks of treatment with glecaprevir/pibrentasvir is efficacious and well tolerated in treatment-naïve patients with HCV genotype 1 to 6 infections, with or without cirrhosis.

• Authors: Eli Zuckerman, Julio A Gutierrez, Douglas E Dylla, Victor de Ledinghen, Andrew J Muir, Michael Gschwantler, Massimo Puoti, Florin Caruntu, Jihad Slim, Frederik Nevens, Samuel Sigal, Stanley Cohen, Linda M Fredrick, Ana Gabriela Pires Dos Santos, Lino Rodrigues Jr, John F Dillon
• Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (Clin Gastroenterol Hepatol) Vol. 18 Issue 11 Pg. 2544-2553.e6 (10 2020) ISSN: 1542-7714 [Electronic] United States
• PMID: 32621971 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

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

Topics

• Aminoisobutyric Acids
• Antiviral Agents (adverse effects)
• Benzimidazoles
• Cyclopropanes
• Genotype
• Hepacivirus (genetics)
• Hepatitis C (drug therapy)
• Hepatitis C, Chronic (complications, drug therapy)
• Humans
• Lactams, Macrocyclic
• Leucine (analogs & derivatives)
• Middle Aged
• Proline (analogs & derivatives)
• Pyrrolidines
• Quinoxalines
• Sulfonamides