Efficacy and safety of a two‐drug direct‐acting antiviral agent regimen ruzasvir 180 mg and uprifosbuvir 450 mg for 12 weeks in adults with chronic hepatitis C virus genotype 1, 2, 3, 4, 5 or 6. Issue 9 (11th July 2019)

• Record Type: Journal Article
• Authors: Lawitz, Eric; Gane, Edward; Feld, Jordan J.; Buti, Maria; Foster, Graham R.; Rabinovitz, Mordechai; Burnevich, Eduard; Katchman, Helena; Tomasiewicz, Krzysztof; Lahser, Fred; Jackson, Beth; Shaughnessy, Melissa; Klopfer, Stephanie; Yeh, Wendy W.; Robertson, Michael N.; Hanna, George J.; Barr, Eliav; Platt, Heather L.
• Other Names: Gordon Stuart C. investigator.; Lawitz Eric J. investigator.; Ruane Peter Jerome investigator.; Sahota Amandeep investigator.; Terrault Norah A. investigator.; Tsai Naoky investigator.; Kalathil Sumodh C. investigator.; Reddy Gautham investigator.; Ghesquiere Wayne investigator.; Borgia Sergio investigator.; Conway Brian investigator.; Feld Jordan investigator.; Tsoi Keith investigator.; Cooper Curtis L. investigator.; Ghali Peter Maged investigator.; Thompson Alexander James Venn investigator.; Panero Jose Luis Calleja investigator.; Ferret Sabela Lens Maria Buti investigator.; Franinan Luis Margusino investigator.; de los Angeles Castro Iglesias Maria investigator.; Brown Ashley investigator.; Agarwal Kaushik investigator.; Foster Graham investigator.; Cramp Matthew investigator.; Zuckerman Eli investigator.; Veitsman Ella investigator.; Cohen Michal investigator.; Lurie Yoav investigator.; Ari Ziv Ben investigator.; Janczewska Ewa investigator.; Szymczak Aleksandra investigator.; Halota Waldemar investigator.; Flisiak Robert investigator.; Mahomed Adam investigator.; Sonderup Mark Wayne investigator.; Punt Zelda Erika investigator.; Kgomo Mpho Klaas investigator.; Bernhardi David C investigator.; Burnevich Eduard Z. investigator.; Kizhlo Svetlana investigator.;
• Is Part Of: Journal of viral hepatitis. Volume 26:Issue 9(2019)
• Page Start: 1127
• Page End: 1138
• Publication Date: 2019-07-11
• Subjects: clinical trial -- efficacy -- genotype -- hepatitis C virus -- safety; Hepatitis, Viral -- Periodicals; Hepatitis, Viral, Animal; Hepatitis, Viral, Human; 616.3623
• DOI: 10.1111/jvh.13132
• Languages: English
• ISSNs: 1352-0504

Abstract

Abstract: Ruzasvir (MK‐8408, an NS5A inhibitor) and uprifosbuvir (MK‐3682, a nonstructural protein 5B nucleotide inhibitor) are highly potent direct‐acting antiviral agents for the treatment of hepatitis C virus (HCV) infection. A phase III clinical trial evaluating the two‐drug combination of ruzasvir 60 mg plus uprifosbuvir 450 mg suggested suboptimal efficacy in certain HCV genotypes (C‐BREEZE 1; NCT02759315). The aim of the present study was to evaluate the efficacy and safety of ruzasvir in combination with uprifosbuvir administered at a higher dose than that assessed in the earlier study (C‐BREEZE 2: NCT02956629/Merck protocol PN041). Treatment‐naïve or interferon (with or without ribavirin)‐experienced participants with or without compensated cirrhosis were enrolled. All participants received ruzasvir 180 mg plus uprifosbuvir 450 mg once daily for 12 weeks. The primary objectives were the proportion of participants with HCV RNA <15 lU/mL at 12 weeks after the end of study therapy (SVR12), and safety and tolerability of the study drug. Overall, 282 participants were enrolled. SVR12 (n/N) was 91.3% (42/46) in participants infected with HCV genotype (GT) 1a; GT1b, 96.7% (29/30); GT2, 91.5% (43/47); GT3, 73.8% (45/61); GT4, 98.2% (55/56); GT5, 100.0% (18/18); and GT6, 90.9% (20/22). Adverse events (AEs) were reported by 61.3% of participants; drug‐related AEs were reported by 33.3%. The most frequent (≥5% of participants) drug‐related AEs in all participants were fatigue (7.8%) and headache (7.4%). In conclusion, the two‐drug combination of ruzasvir 180 mg plus uprifosbuvir 450 mg for 12 weeks was highly effective and well tolerated in participants infected with HCV GT1, GT2, GT4, GT5 and GT6, with a lower efficacy in GT3‐infected persons.