Efficacy and Safety of Glecaprevir/Pibrentasvir in Participants with Chronic HCV Infection and Comorbidities or Multiple Concomitant Medications: An Integrated Analysis

Introduction: Glecaprevir/pibrentasvir (G/P) is globally approved for the treatment of chronic hepatitis C virus (HCV) infection and for acute HCV infection in the USA. The efficacy and safety of G/P has been clinically demonstrated in participants with chronic HCV. We used clinical trial data to assess the efficacy, safety, and tolerability of G/P in participants with comorbidities or on multiple concomitant medications with potential for drug–drug interaction with G/P. Methods: An integrated pooled analysis across 21 randomized, controlled phase 2 and 3 trials of participants who received G/P for 8, 12, or 16 weeks was performed. Participants were stratified by comorbidity or population of interest and by number of concomitant medications received. Results: This analysis included 6547 participants with chronic HCV infection. Overall, 2068 (31.6%) had cardiovascular disorders, 2031 (31.0%) reported illicit drug use, 1373/4617 (29.7%) reported injection drug use, 1810 (27.6%) had psychiatric disorders, 1169 (17.9%) had compensated cirrhosis, and 291 (4.4%) had human immunodeficiency virus (HIV)–HCV coinfection. Additionally, 4524 (69.1%) were receiving ≥ 1 concomitant medication. According to the Liverpool HEP Drug Interactions checker, 1357 (20.7%) were receiving a concomitant medication with mechanistic potential or weak potential drug–drug interaction with G/P. Overall, 94.3% (6174/6547) achieved sustained virologic response at 12 weeks post-treatment (SVR12: 98.7% [6174/6257] when excluding non-virologic treatment failure), with consistent rates between subgroups. In total, 3140 (48.0%) of participants experienced an adverse event (AE) and 1638 (25.0%) experienced a treatment-related AE. Serious AEs and treatment-related serious AEs were observed in 165 (2.5%) and 6 (0.1%) participants, respectively. In subgroup analyses, the highest rate of treatment-related serious AEs was observed in participants with HIV–HCV coinfection (0.7%). Mean compliance was 99.6%, which was consistent across subgroups and by number of concomitant medications received. Conclusions: These pooled data support the efficacy, safety, and tolerability of G/P in participants with chronic HCV infection and comorbidities or who are on multiple concomitant medications.