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

• Published in: Journal of hepatology Vol. 72; no. 3; pp. 441 - 449
• Main Authors: Brown, Robert S., Buti, Maria, Rodrigues, Lino, Chulanov, Vladimir, Chuang, Wan-Long, Aguilar, Humberto, Horváth, Gábor, Zuckerman, Elimelech, Carrion, Barbara Rosado, Rodriguez-Perez, Federico, Urbánek, Petr, Abergel, Armand, Cohen, Eric, Lovell, Sandra S., Schnell, Gretja, Lin, Chih-Wei, Zha, Jiuhong, Wang, Stanley, Trinh, Roger, Mensa, Federico J., Burroughs, Margaret, Felizarta, Franco
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2020; Elsevier Science Ltd
• Subjects: Aged; Aminoisobutyric Acids - administration & dosage; Aminoisobutyric Acids - adverse effects; Antiviral Agents - administration & dosage; Antiviral Agents - adverse effects; Benzimidazoles - administration & dosage; Benzimidazoles - adverse effects; Chronic HCV infection; Chronic infection; Cirrhosis; Compensated cirrhosis; Cyclopropanes - administration & dosage; Cyclopropanes - adverse effects; Direct-acting antiviral; Drug Combinations; Female; Genotype; Genotypes; Glecaprevir/pibrentasvir; HCV elimination; Headache; Hepacivirus - enzymology; Hepacivirus - genetics; Hepatitis C virus; Hepatitis C, Chronic - blood; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - virology; Humans; Lactams, Macrocyclic - administration & dosage; Lactams, Macrocyclic - adverse effects; Leucine - administration & dosage; Leucine - adverse effects; Leucine - analogs & derivatives; Liver cirrhosis; Liver Cirrhosis - complications; Liver Cirrhosis - drug therapy; Male; Middle Aged; Nausea; Pangenotypic; Polymorphism, Genetic; Population; Proline - administration & dosage; Proline - adverse effects; Proline - analogs & derivatives; Pruritus; Pyrrolidines - administration & dosage; Pyrrolidines - adverse effects; Quinoxalines - administration & dosage; Quinoxalines - adverse effects; RNA, Viral - blood; RNA, Viral - genetics; Short duration; Sulfonamides - administration & dosage; Sulfonamides - adverse effects; Sustained Virologic Response; Viral Nonstructural Proteins - genetics; Short duration; HCV elimination; Pangenotypic; Direct-acting antiviral; Glecaprevir/pibrentasvir; Compensated cirrhosis; Chronic HCV infection; Hepatitis C virus
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2019.10.020

[Display omitted] •343 treatment-naïve patients with chronic HCV genotypes 1–6 and compensated cirrhosis.•Glecaprevir/pibrentasvir for 8 weeks achieved 99.7% virologic cure.•One patient experienced relapse at post-treatment week 4.•Efficacy did not depend on any pre-treatment patient or viral characteristics.•No drug-related serious adverse events or discontinuations due to adverse events occurred. Eight-week glecaprevir/pibrentasvir leads to high rates of sustained virological response at post-treatment week 12 (SVR12) across HCV genotypes (GT) 1–6 in treatment-naïve patients without cirrhosis. We evaluated glecaprevir/pibrentasvir once daily for 8 weeks in treatment-naïve patients with compensated cirrhosis. EXPEDITION-8 was a single-arm, multicenter, phase IIIb trial. The primary and key secondary efficacy analyses were to compare the lower bound of the 95% CI of the SVR12 rate in i) patients with GT1,2,4–6 in the per protocol (PP) population, ii) patients with GT1,2,4–6 in the intention-to-treat (ITT) population, iii) patients with GT1–6 in the PP population, and iv) 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. A total of 343 patients were 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. Eight-week glecaprevir/pibrentasvir was well tolerated and led to a similarly high SVR12 rate as the 12-week regimen in treatment-naïve patients with chronic HCV GT1–6 infection and compensated cirrhosis. Trial registration: ClinicalTrials.gov, NCT03089944. This study was the first to evaluate an 8-week direct-acting antiviral (DAA) regimen active against all major types of hepatitis C virus (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. This may simplify care and allow non-specialist healthcare professionals to treat these patients, contributing to global efforts to eliminate HCV.