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

Abstract 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.