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

• Published in: Journal of viral hepatitis Vol. 26; no. 9; pp. 1127 - 1138
• Main 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., Gordon, Stuart C., Lawitz, Eric J., Ruane, Peter Jerome, Sahota, Amandeep, Terrault, Norah A., Tsai, Naoky, Kalathil, Sumodh C., Reddy, Gautham, Ghesquiere, Wayne, Borgia, Sergio, Conway, Brian, Feld, Jordan, Tsoi, Keith, Cooper, Curtis L., Ghali, Peter Maged, Thompson, Alexander James Venn, Panero, Jose Luis Calleja, Ferret, Sabela Lens Maria Buti, Franinan, Luis Margusino, Angeles Castro Iglesias, Maria, Brown, Ashley, Agarwal, Kaushik, Foster, Graham, Cramp, Matthew, Zuckerman, Eli, Veitsman, Ella, Cohen, Michal, Lurie, Yoav, Ari, Ziv Ben, Janczewska, Ewa, Szymczak, Aleksandra, Halota, Waldemar, Flisiak, Robert, Mahomed, Adam, Sonderup, Mark Wayne, Punt, Zelda Erika, Kgomo, Mpho Klaas, Bernhardi, David C, Burnevich, Eduard Z., Kizhlo, Svetlana
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.09.2019
• Subjects: Antiviral agents; Cirrhosis; clinical trial; efficacy; genotype; Genotypes; Headache; Hepatitis; Hepatitis C; hepatitis C virus; Interferon; Liver cirrhosis; Nonstructural protein 5B; Ribavirin; Ribonucleic acid; RNA; Safety; clinical trial; hepatitis C virus; safety; efficacy; genotype
• ISSN: 1352-0504; 1365-2893
• DOI: 10.1111/jvh.13132

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.