Efficacy and safety of glecaprevir/pibrentasvir in patients with HCV genotype 5/6: An integrated analysis of phase 2/3 studies

BACKGROUND & AIMS: Hepatitis C virus (HCV) has high genetic diversity with six major genotypes (GT) GT1‐6 and global distribution. HCV GT5 and 6 are rare with < 10 million people infected worldwide. Data on direct‐acting antiviral use in these rare HCV genotypes are limited. The study aimed to evaluate the efficacy and safety of glecaprevir/pibrentasvir (G/P) in a pooled analysis of phase 2/3 trials in HCV GT5 or 6‐infected patients without cirrhosis or with compensated cirrhosis. METHODS: Patients with chronic HCV GT5 or 6 infection received oral G/P (300 mg/120 mg) once daily for 8 or 12 weeks. The primary efficacy endpoint was sustained virological response at post‐treatment week 12 (SVR12) in the intention‐to‐treat population. RESULTS: One hundred eighty‐one patients were evaluated; 56 with HCV GT5 and 125 with HCV GT6. The majority were treatment‐naïve (88%) and non‐cirrhotic (85%). Overall SVR12 rate with 8‐ or 12‐week G/P treatment was 98% (178/181). Eight‐week treatment with G/P yielded SVR12 rates of 95% (21/22) in HCV GT5‐ and 99% (69/70) in HCV GT6‐infected non‐cirrhotic patients. Eight‐ and 12‐week treatment of patients with compensated cirrhosis achieved SVR12 rates of 100% (10/10) and 94% (17/18) respectively. The G/P regimen was well‐tolerated; 3% (6/181) Grade 3 or higher adverse events, and no serious adverse events were attributed to G/P or led to study drug discontinuation. CONCLUSIONS: This integrated dataset demonstrates a high SVR12 rate following 8‐week G/P treatment in patients with HCV GT5 (96%) or GT6 (99%) infection without cirrhosis or with compensated cirrhosis.