Tarik Asselah1, Samuel S Lee2, Betty B Yao3, Tuan Nguyen4, Florence Wong5, Adam Mahomed6, Seng Gee Lim7, Armand Abergel8, Joe Sasadeusz9, Edward Gane10, Neddie Zadeikis3, Gretja Schnell3, Zhenzhen Zhang3, Ariel Porcalla3, Federico J Mensa3, Kinh Nguyen11. 1. Centre de Recherche sur l'Inflammation, INSERM UMR 1149, Université Paris Diderot, Department of Hepatology, AP-HP Hôpital Beaujon, Clichy, France. Electronic address: tarik.asselah@aphp.fr. 2. University of Calgary, Calgary, AB, Canada. 3. AbbVie Inc, North Chicago, IL, USA. 4. Research and Education, Inc, San Diego, CA, USA. 5. Toronto General Hospital, University of Toronto, Toronto, ON, Canada. 6. Department of Gastroenterology and Hepatology, Faculty of Health Sciences, University of Witwatersrand, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa. 7. Division of Gastroenterology and Hepatology, National University Health System, Singapore. 8. CHU Estaing, Clermont Ferrand, France. 9. Royal Melbourne Hospital, Melbourne, VIC, Australia. 10. Auckland Clinical Studies, Auckland, New Zealand. 11. National Hospital for Tropical Diseases, Hanoi, Vietnam.
Abstract
BACKGROUND: The pangenotypic direct-acting antiviral regimen of glecaprevir coformulated with pibrentasvir is approved to treat chronic hepatitis C virus (HCV) genotype 1-6 infection in adults. In registrational studies, 84 (99%) of 85 patients with HCV genotype 5 or 6 infection achieved a sustained virological response (SVR) with glecaprevir/pibrentasvir, with no virological failures. To increase the body of data for these less prevalent genotypes, ENDURANCE-5,6 evaluated the efficacy and safety of glecaprevir/pibrentasvir exclusively in patients infected with HCV genotype 5 or 6. METHODS: ENDURANCE-5,6 was a phase 3b, single-arm, open-label, multicentre trial done in 24 hospitals or clinics in Europe, Oceania, North America, South Africa, and southeast Asia. Adults with chronic HCV genotype 5 or 6 infection who were previously untreated or treatment-experienced were eligible to be enrolled. Glecaprevir/pibrentasvir (300 mg/120 mg) was given orally once daily for 8 weeks (for patients without cirrhosis) or 12 weeks (for patients with compensated cirrhosis). The primary efficacy endpoint was SVR12 (ie, HCV RNA <15 IU/mL at 12 weeks post-treatment), assessed within each HCV genotype, and analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02966795. FINDINGS: Between Feb 9, 2017, and Aug 28, 2018, 84 patients were enrolled: 23 with genotype 5 infection and 61 with genotype 6 infection. Overall, 82 (97·6%, 95% CI 94·4-100·0) of the 84 patients achieved SVR12. 22 (95·7%, 95% CI 87·3-100·0) of 23 patients with genotype 5 infection achieved SVR12, as did 60 (98·4%, CI 95·2-100·0) of 61 with genotype 6 infection. One patient with an HCV genotype 6f infection and cirrhosis had on-treatment virological failure at treatment week 12, and one patient with HCV genotype 5a without cirrhosis who had achieved SVR at post-treatment week 4 relapsed at post-treatment week 12. Five (6%) patients had serious adverse events, none of which were deemed related to glecaprevir/pibrentsavir or led to discontinuation. Fatigue (11 [13%] patients) and headache (11 [13%]) were the only adverse events that occurred in 10% or more of patients. No post-baseline grade 3 or higher increases in aminotransferase concentrations were reported. INTERPRETATION: Glecaprevir/pibrentasvir achieved high SVR12 rates, comparable with data reported in registrational studies, and was well tolerated in patients with HCV genotype 5 or 6 infection with compensated liver disease. FUNDING: AbbVie.
BACKGROUND: The pangenotypic direct-acting antiviral regimen of glecaprevir coformulated with pibrentasvir is approved to treat chronic hepatitis C virus (HCV) genotype 1-6 infection in adults. In registrational studies, 84 (99%) of 85 patients with HCV genotype 5 or 6 infection achieved a sustained virological response (SVR) with glecaprevir/pibrentasvir, with no virological failures. To increase the body of data for these less prevalent genotypes, ENDURANCE-5,6 evaluated the efficacy and safety of glecaprevir/pibrentasvir exclusively in patients infected with HCV genotype 5 or 6. METHODS: ENDURANCE-5,6 was a phase 3b, single-arm, open-label, multicentre trial done in 24 hospitals or clinics in Europe, Oceania, North America, South Africa, and southeast Asia. Adults with chronic HCV genotype 5 or 6 infection who were previously untreated or treatment-experienced were eligible to be enrolled. Glecaprevir/pibrentasvir (300 mg/120 mg) was given orally once daily for 8 weeks (for patients without cirrhosis) or 12 weeks (for patients with compensated cirrhosis). The primary efficacy endpoint was SVR12 (ie, HCV RNA <15 IU/mL at 12 weeks post-treatment), assessed within each HCV genotype, and analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02966795. FINDINGS: Between Feb 9, 2017, and Aug 28, 2018, 84 patients were enrolled: 23 with genotype 5 infection and 61 with genotype 6 infection. Overall, 82 (97·6%, 95% CI 94·4-100·0) of the 84 patients achieved SVR12. 22 (95·7%, 95% CI 87·3-100·0) of 23 patients with genotype 5 infection achieved SVR12, as did 60 (98·4%, CI 95·2-100·0) of 61 with genotype 6 infection. One patient with an HCV genotype 6f infection and cirrhosis had on-treatment virological failure at treatment week 12, and one patient with HCV genotype 5a without cirrhosis who had achieved SVR at post-treatment week 4 relapsed at post-treatment week 12. Five (6%) patients had serious adverse events, none of which were deemed related to glecaprevir/pibrentsavir or led to discontinuation. Fatigue (11 [13%] patients) and headache (11 [13%]) were the only adverse events that occurred in 10% or more of patients. No post-baseline grade 3 or higher increases in aminotransferase concentrations were reported. INTERPRETATION:Glecaprevir/pibrentasvir achieved high SVR12 rates, comparable with data reported in registrational studies, and was well tolerated in patients with HCV genotype 5 or 6 infection with compensated liver disease. FUNDING: AbbVie.
Authors: Betty B Yao; Linda M Fredrick; Gretja Schnell; Kris V Kowdley; Paul Y Kwo; Fred Poordad; Kinh Nguyen; Samuel S Lee; Christophe George; Florence Wong; Edward Gane; Armand Abergel; Catherine W Spearman; Tuan Nguyen; Manh Hung Le; Thuy Tt Pham; Federico Mensa; Tarik Asselah Journal: Liver Int Date: 2020-06-11 Impact factor: 5.828
Authors: Barnaby Flower; Jonathan C Brown; Wendy S Barclay; Graham S Cooke; Bryony Simmons; Maya Moshe; Rebecca Frise; Rebecca Penn; Ruthiran Kugathasan; Claire Petersen; Anna Daunt; Deborah Ashby; Steven Riley; Christina Joanne Atchison; Graham P Taylor; Sutha Satkunarajah; Lenny Naar; Robert Klaber; Anjna Badhan; Carolina Rosadas; Maryam Khan; Natalia Fernandez; Macià Sureda-Vives; Hannah M Cheeseman; Jessica O'Hara; Gianluca Fontana; Scott J C Pallett; Michael Rayment; Rachael Jones; Luke S P Moore; Myra O McClure; Peter Cherepanov; Richard Tedder; Hutan Ashrafian; Robin Shattock; Helen Ward; Ara Darzi; Paul Elliot Journal: Thorax Date: 2020-08-12 Impact factor: 9.102