Glecaprevir/pibrentasvir for 8 weeks in treatment-naïve patients with chronic HCV genotypes 1–6 and compensated cirrhosis: The EXPEDITION-8 trial

Abstract Background & Aims 8-week glecaprevir/pibrentasvir demonstrates high rates of sustained virological response at post-treatment week 12 (SVR12) across hepatitis C virus (HCV) genotypes (GT) 1–6 in treatment-naive patients without cirrhosis. We evaluated glecaprevir/pibrentasvir once daily for 8 weeks in treatment-naive patients with compensated cirrhosis. Methods EXPEDITION-8 was a single-arm, multicenter, phase 3b trial. The primary and key secondary efficacy analyses were to compare the lower bound of the 95% confidence interval (CI) of the SVR12 rate in (1) patients with GT1,2,4–6 in the per-protocol (PP) population, (2) patients with GT1,2,4–6 in the intention-to-treat (ITT) population, (3) patients with GT1–6 in the PP population, and (4) patients with GT1–6 in the ITT population, to pre-defined efficacy thresholds based on historical SVR12 rates for 12 weeks of glecaprevir/pibrentasvir in the same populations. Safety was also assessed. This trial is registered with ClinicalTrials.gov, NCT03089944. Results 343 patients enrolled. Most patients were male (63%), white (83%), and had GT1 (67%). The SVR12 rate in patients with GT1–6 was 99.7% (n/N=334/335; 95%CI, 98.3–99.9) in the PP population and 97.7% (n/N=335/343; 95%CI, 96.1–99.3) in the ITT population. All primary and key secondary efficacy analyses were achieved. One patient (GT3a) experienced relapse (0.3%) at post-treatment week 4. Common adverse events (≥5%) were fatigue (9%), pruritus (8%), headache (8%), and nausea (6%). Serious adverse events (none related) occurred in 2% of patients. No adverse event led to study drug discontinuation. Clinically significant laboratory abnormalities were infrequent. Conclusions 8-week glecaprevir/pibrentasvir was well tolerated and achieved a similarly high SVR12 rate versus the 12-week regimen in treatment-naive patients with chronic HCV GT1–6 infection and compensated cirrhosis. Lay summary The availability of an 8-week, oral, direct-acting antiviral (DAA) regimen for patients with chronic hepatitis C virus (HCV) infection who have not yet received treatment, regardless of whether they are non-cirrhotic or have compensated cirrhosis, may simplify the care of these patients. This may allow non-specialist healthcare professionals to treat these patients, contributing to global efforts to eliminate HCV. This study was the first to evaluate an 8-week DAA regimen active against all major types of HCV in untreated patients with compensated cirrhosis. High virological cure rates were achieved with glecaprevir/pibrentasvir across HCV genotypes 1–6, and these high cure rates did not depend on any patient or viral characteristics present before treatment. Common side effects of glecaprevir/pibrentasvir were tiredness, itching, headache, and nausea. The safety profile of glecaprevir/pibrentasvir was consistent with previous studies and no new safety issues were identified.