Safety and Pharmacokinetics of Glecaprevir/Pibrentasvir in Adults With Chronic Genotype 1-6 Hepatitis C Virus Infections and Compensated Liver Disease

Edward Gane, Fred Poordad, Neddie Zadeikis, Joaquin Valdes, Chih-Wei Lin, Wei Liu, Armen Asatryan, Stanley Wang, Catherine Stedman, Susan Greenbloom, Tuan Nguyen, Magdy Elkhashab, Marcus-Alexander Wörns, Albert Tran, Jean-Pierre Mulkay, Carolyn Setze, Yao Yu, Tami Pilot-Matias, Ariel Porcalla, Federico J Mensa, Edward Gane, Fred Poordad, Neddie Zadeikis, Joaquin Valdes, Chih-Wei Lin, Wei Liu, Armen Asatryan, Stanley Wang, Catherine Stedman, Susan Greenbloom, Tuan Nguyen, Magdy Elkhashab, Marcus-Alexander Wörns, Albert Tran, Jean-Pierre Mulkay, Carolyn Setze, Yao Yu, Tami Pilot-Matias, Ariel Porcalla, Federico J Mensa

Abstract

Background: Untreated, chronic hepatitis C virus (HCV) infection may lead to progressive liver damage, which can be mitigated by successful treatment. This integrated analysis reports the safety, efficacy, and pharmacokinetics (PK) of the ribavirin-free, direct-acting, antiviral, fixed-dose combination of glecaprevir/pibrentasvir (G/P) in patients with chronic HCV genotype 1-6 infections and compensated liver disease, including patients with chronic kidney disease stages 4 or 5 (CKD 4/5).

Methods: Data from 9 Phase II and III clinical trials, assessing the efficacy and safety of G/P treatment for 8-16 weeks, were included. The presence of cirrhosis was determined at screening using a liver biopsy, transient elastography, or serum biomarkers. The objectives were to evaluate safety, the rate of sustained virologic response at post-treatment week 12 (SVR12), and steady-state PK by cirrhosis status.

Results: Among 2369 patients, 308 (13%) were Child-Pugh Class A, including 20 with CKD 4/5. Overall, <1% of patients experienced an adverse event (AE) that led to G/P discontinuation or G/P-related serious AEs (SAEs). The most common AEs were headache and fatigue, occurring at similar frequencies with and without cirrhosis. SAEs were more common in patients with CKD 4/5, but all were unrelated to G/P. There were no cases of drug-induced liver injury or clinically relevant hepatic decompensation. SVR12 rates were 96.4% (297/308) with compensated cirrhosis and 97.5% (2010/2061) without cirrhosis. PK analysis demonstrated a 2.2-fold increase in glecaprevir exposure, but not pibrentasvir exposure, in patients with compensated cirrhosis.

Conclusions: G/P was safe and efficacious in patients with compensated liver disease, including those with CKD 4/5.

Clinical trials registration: NCT02243280, NCT02243293, NCT02604017, NCT02640482, NCT02640157, NCT02636595, NCT02642432, NCT02651194, and NCT02446717.

Keywords: HCV; adverse event; chronic kidney disease; compensated cirrhosis; glecaprevir/pibrentasvir.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Sustained virologic response at 12 weeks post-treatment (SVR12) by cirrhosis status and HCV genotype. Glecaprevir/pibrentasvir efficacy, defined as SVR12, reported by cirrhosis status and further stratified by HCV GT using ITT (A) and modified ITT (B) analyses. Abbreviations: GT, genotype; HCV, hepatitis C virus; ITT, intent-to-treat.

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