Glecaprevir plus pibrentasvir for chronic hepatitis C virus genotype 1, 2, 4, 5, or 6 infection in adults with compensated cirrhosis (EXPEDITION-1): a single-arm, open-label, multicentre phase 3 trial

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From: The Lancet Infectious Diseases(Vol. 17, Issue 10)
Publisher: Elsevier B.V.
Document Type: Article
Length: 634 words

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To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1016/S1473-3099(17)30496-6 Byline: Dr Xavier Forns, MD [xforns@clinic.cat] (a,*), Prof Samuel S Lee, MD (b), Joaquin Valdes, MD (c), Sabela Lens, MD (a), Reem Ghalib, MD (d), Humberto Aguilar, MD (e), Franco Felizarta, MD (f), Tarek Hassanein, MD (g), Holger Hinrichsen, MD (h), Diego Rincon, MD (i), Rosa Morillas, MD (j), Prof Stefan Zeuzem, MD (k), Yves Horsmans, MD (l), Prof David R Nelson, MD (m), Yao Yu, PhD (c), Preethi Krishnan, PhD (c), Chih-Wei Lin, PhD (c), Jens J Kort, MD (c), Federico J Mensa, MD (c) Summary Background The once-daily, ribavirin-free, pangenotypic, direct-acting antiviral regimen, glecaprevir coformulated with pibrentasvir, has shown high rates of sustained virological response in phase 2 and 3 studies. We aimed to assess the efficacy and safety of 12 weeks of coformulated glecaprevir and pibrentasvir in patients with hepatitis C virus (HCV) infection and compensated cirrhosis. Methods We did this single-arm, open-label, multicentre phase 3 study at 40 sites in Belgium, Canada, Germany, South Africa, Spain, and the USA. We enrolled patients aged 18 years or older with HCV genotype 1, 2, 4, 5, or 6 infection and compensated cirrhosis. Patients were either HCV treatment-naive or had not responded to treatment with interferon or pegylated interferon with or without ribavirin, or sofosbuvir plus ribavirin with or without pegylated interferon. Oral glecaprevir (300 mg) coformulated with pibrentasvir (120 mg) was administered once daily for 12 weeks. The primary efficacy endpoint was sustained virological response at post-treatment week 12 (HCV RNA Findings Between Dec 7, 2015, and May 4, 2016, we enrolled 146 patients with compensated cirrhosis, of whom 48 (33%) had genotype 1a HCV infection, 39 (27%) had genotype 1b infection, 34 (23%) had genotype 2 infection, 16 (11%) had genotype 4 infection, two (1%) had genotype 5 infection, and seven (5%) had genotype 6 infection. 12 weeks after treatment, 145 patients (99%, 95% CI 98--100) achieved sustained virological response, with one (1%) relapse at post-treatment week 8. We recorded 101 (69%) adverse events, of which 65 (64%) were mild. The most common adverse events were fatigue (n=28 [19%]) and headache (n=20 [14%]). 11 (8%) patients had serious adverse events, none of which were deemed related to study drugs. No patients had elevations in alanine aminotransferase and no patients prematurely discontinued treatment because of adverse events. Interpretation Our results show that 99% of patients treated with once-daily glecaprevir plus pibrentasvir achieved a sustained virological response at 12 weeks. Furthermore, this drug regimen had a favourable safety profile in previously treated or untreated patients with chronic HCV genotype 1, 2, 4, 5, or 6 infection and compensated cirrhosis. These findings could help simplify treatment algorithms and reduce treatment burden. Funding AbbVie. Author Affiliation: (a) Liver Unit, Hospital Clinic, CIBEREHD, IDIBAPS, University of Barcelona, Barcelona, Spain (b) University of Calgary, Calgary, AB, Canada (c) AbbVie, North Chicago, IL, USA (d) Texas Digestive Disease Consultants, Arlington, TX, USA (e) Louisiana Research Center, Shreveport, LA, USA (f) Private Practice, Bakersfield, CA, USA (g) Southern California Liver Centers and Southern California Research Center, Coronado, CA, USA (h) Gastroenterology--Hepatology Center Kiel, Kiel, Germany (i) Liver Unit, Hospital General Universitario Gregorio Maranon, CIBERehd, Madrid, Spain (j) Liver Section and CIBERehd, Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain (k) Johann Wolfgang Goethe University, Frankfurt, Germany (l) Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Brussels, Belgium (m) Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA * Correspondence to: Dr Xavier Forns, Liver Unit, Hospital Clinic, CIBEREHD, IDIBAPS, Barcelona 08036, Spain

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Gale Document Number: GALE|A522636888