Eli Zuckerman1, Julio A Gutierrez2, Douglas E Dylla3, Victor de Ledinghen4, Andrew J Muir5, Michael Gschwantler6, Massimo Puoti7, Florin Caruntu8, Jihad Slim9, Frederik Nevens10, Samuel Sigal11, Stanley Cohen12, Linda M Fredrick3, Ana Gabriela Pires Dos Santos3, Lino Rodrigues3, John F Dillon13. 1. Liver Unit, Carmel Medical Center, Faculty of Medicine, Technion Institute, Haifa, Israel. Electronic address: elizuc56@gmail.com. 2. Scripps Clinic, Center for Organ and Cell Transplantation, La Jolla, California. 3. AbbVie, Inc, North Chicago, Illinois. 4. Centre d'Investigation de la Fibrose Hépatique, Bordeaux University Hospital, Pessac, France; INSERM U1053, Bordeaux University, Bordeaux, France. 5. Duke Clinical Research Institute, Durham, North Carolina. 6. Department of Internal Medicine IV, Wilhelminenspital, Vienna, Austria; Sigmund Freud University, Vienna, Austria. 7. Niguarda ca Grande Hospital, Milan, Italy. 8. National Institute for Infectious Diseases "Prof. Matei Bals," Bucharest, Romania. 9. Infectious Disease Division, Department of Internal Medicine, St. Michael's Medical Center, Newark, New Jersey. 10. Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Belgium. 11. Montefiore Medical Center, Bronx, New York. 12. UH Cleveland Medical Center, Cleveland, Ohio. 13. Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, United Kingdom.
Abstract
BACKGROUND & AIMS: The direct-acting antiviral combination glecaprevir/pibrentasvir has been approved by the Food and Drug Administration for 8 weeks of treatment in treatment-naïve patients with hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis. We performed an integrated analysis of data from trials to evaluate the overall efficacy and safety of 8 weeks of glecaprevir/pibrentasvir in treatment-naïve patients without cirrhosis or with compensated cirrhosis. METHODS: We pooled data from 8 phase 2 or phase 3 trials of treatment-naïve patients with HCV genotype 1 to 6 infections, without cirrhosis or with compensated cirrhosis, who received 8 weeks of glecaprevir/pibrentasvir. RESULTS: Of 1248 patients, 343 (27%) had cirrhosis. Most patients were white (80%) and had HCV genotype 1 infection (47%) or genotype 3 infection (22%); the median age was 54 years. Overall rates of sustained virologic response at post-treatment week 12 were 97.6% (1218 of 1248) in the intention to treat (ITT) and 99.3% (1218 of 1226) in the modified ITT populations. When we excluded patients with genotype 3 infections with compensated cirrhosis (consistent with the European label), rates of sustained virologic response at post-treatment week 12 were 97.6% in the ITT and 99.4% in the modified ITT populations. Eight virologic failures (7 in patients without cirrhosis and 1 in a patient with cirrhosis) occurred in the ITT population. Virologic failure was not associated with markers of advanced liver disease or populations of interest (current alcohol use, opioid substitution therapy, history of injection-drug use, and severe renal impairment). Treatment-emergent adverse events (AEs) occurred in 58% of patients. The most frequent AEs (>10%) were headache (12%) and fatigue (12%). Serious AEs and AEs that led to glecaprevir/pibrentasvir discontinuation were reported in 2% and less than 1% of patients, respectively. CONCLUSIONS: In a pooled analysis of data from 8 trials, we found that 8 weeks of treatment with glecaprevir/pibrentasvir is efficacious and well tolerated in treatment-naïve patients with HCV genotype 1 to 6 infections, with or without cirrhosis.
BACKGROUND & AIMS: The direct-acting antiviral combination glecaprevir/pibrentasvir has been approved by the Food and Drug Administration for 8 weeks of treatment in treatment-naïve patients with hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis. We performed an integrated analysis of data from trials to evaluate the overall efficacy and safety of 8 weeks of glecaprevir/pibrentasvir in treatment-naïve patients without cirrhosis or with compensated cirrhosis. METHODS: We pooled data from 8 phase 2 or phase 3 trials of treatment-naïve patients with HCV genotype 1 to 6 infections, without cirrhosis or with compensated cirrhosis, who received 8 weeks of glecaprevir/pibrentasvir. RESULTS: Of 1248 patients, 343 (27%) had cirrhosis. Most patients were white (80%) and had HCV genotype 1 infection (47%) or genotype 3 infection (22%); the median age was 54 years. Overall rates of sustained virologic response at post-treatment week 12 were 97.6% (1218 of 1248) in the intention to treat (ITT) and 99.3% (1218 of 1226) in the modified ITT populations. When we excluded patients with genotype 3 infections with compensated cirrhosis (consistent with the European label), rates of sustained virologic response at post-treatment week 12 were 97.6% in the ITT and 99.4% in the modified ITT populations. Eight virologic failures (7 in patients without cirrhosis and 1 in a patient with cirrhosis) occurred in the ITT population. Virologic failure was not associated with markers of advanced liver disease or populations of interest (current alcohol use, opioid substitution therapy, history of injection-drug use, and severe renal impairment). Treatment-emergent adverse events (AEs) occurred in 58% of patients. The most frequent AEs (>10%) were headache (12%) and fatigue (12%). Serious AEs and AEs that led to glecaprevir/pibrentasvir discontinuation were reported in 2% and less than 1% of patients, respectively. CONCLUSIONS: In a pooled analysis of data from 8 trials, we found that 8 weeks of treatment with glecaprevir/pibrentasvir is efficacious and well tolerated in treatment-naïve patients with HCV genotype 1 to 6 infections, with or without cirrhosis.
Authors: Edward Gane; Victor de Ledinghen; Douglas E Dylla; Giuliano Rizzardini; Mitchell L Shiffman; Stephen T Barclay; Jose Luis Calleja; Zhenyi Xue; Margaret Burroughs; Julio A Gutierrez Journal: J Viral Hepat Date: 2021-09-08 Impact factor: 3.517
Authors: Xavier Forns; Jordan J Feld; Douglas E Dylla; Stanislas Pol; Kazuaki Chayama; Jinlin Hou; Jeong Heo; Pietro Lampertico; Ashley Brown; Mark Bondin; Fernando Tatsch; Margaret Burroughs; John Marcinak; Zhenzhen Zhang; Amanda Emmett; Stuart C Gordon; Ira M Jacobson Journal: Adv Ther Date: 2021-05-22 Impact factor: 3.845
Authors: Robert S Brown; Michelle A Collins; Simone I Strasser; Amanda Emmett; Andrew S Topp; Margaret Burroughs; Rosa Ferreira; Jordan J Feld Journal: Infect Dis Ther Date: 2022-02-17