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

  title={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},
  author={Eric Lawitz and Edward Gane and Jordan J. Feld and Mar{\'i}a Buti and Graham R Foster and Mordechai Rabinovitz and Eduard Z. Burnevich and Helena Katchman and Krzysztof Tomasiewicz and Frederick C. Lahser and Beth Jackson and Melissa Shaughnessy and Stephanie Olsen Klopfer and Wendy W. Yeh and Michael N Robertson and George J Hanna and Eliav Barr and Heather L. Platt and Stuart C. Gordon and Eric Lawitz and Peter Ruane and Amandeep K. Sahota and Norah A. Terrault and Naoky C. Tsai and Sumodh C. Kalathil and Gautham Reddy and Wayne Ghesquiere and Sergio M. Borgia and Brian Conway and Jordan J. Feld and Keith Tsoi and Curtis L. Cooper and Peter Ghali and Alexander James Venn Thompson and Jos{\'e} Luis Calleja Panero and Sabela Lens Maria Buti Ferret and Luis Margusino Franinan and Maria Angeles Castro Iglesias and Ashley Brown and Kaushik Agarwal and Graham Foster and Matthew E. Cramp and Eli Zuckerman and E Veitsman and Michal Cohen and Y. E. Lurie and Ziv Ben Ari and Ewa Janczewska and Aleksandra Szymczak and Waldemar Halota and Robert Flisiak and Adam Mahomed and Mark W. Sonderup and Zelda Erika Punt and Mpho Klaas Kgomo and David C Bernhardi and Eduard Z. Burnevich and Svetlana N. Kizhlo},
  journal={Journal of Viral Hepatitis},
  pages={1127 - 1138}
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… Expand
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Paper Mentions

Interventional Clinical Trial
This is a nonrandomized, multi-site, open-label trial to evaluate a novel two-drug combination regimen (uprifosbuvir [MK-3682] 450 mg + ruzasvir [RZR; MK-8408] 180 mg once daily… Expand
ConditionsHepatitis C
Interventional Clinical Trial
This study is an open-label, multi-center trial to evaluate the novel 2-drug regimen of uprifosbuvir (MK-3682) 450 mg and ruzasvir (MK-8408) 60 mg in participants with chronic… Expand
ConditionsHepatitis C, Chronic
Safety, Pharmacokinetics, and Antiviral Activity of AT-527, a Novel Purine Nucleotide Prodrug, in Hepatitis C Virus-Infected Subjects with or without Cirrhosis
Safety and antiviral activity data from this study warrant continued clinical development of AT-527 dosed once daily, with rapid, potent, dose/exposure-related, and pangenotypic antiviralActivity with similar responses between subjects with and without cirrhosis. Expand
Genotype 3-hepatitis C virus’ last line of defense
Although the implementation of highly effective pangenotypic regimens is the most recent stage of revolution in the treatment of GT3 infection, there is still room for improvement, especially in patients with liver cirrhosis and those who fail to respond to DAA therapies, particularly those containing inhibitors of HCV nonstructural protein 5A. Expand
Hepatitis C genotype 4: A report on resistance‐associated substitutions in NS3, NS5A, and NS5B genes
FN performed the literature review and wrote the manuscript; STZ coauthored, edited, and reviewed the manuscript.


Grazoprevir, ruzasvir, and uprifosbuvir for hepatitis C virus after NS5A treatment failure
Grazoprevir, ruzasvir, and uprifosbuvir, with or without ribavirin, for 16 or 24 weeks was safe and highly effective in participants with HCV infection who had previously failed NS5A inhibitor–containing therapy. Expand
Effect of Minor Populations of NS5A and NS5B Resistance-Associated Variants on HCV Genotype-3 Response to Daclatasvir plus Sofosbuvir, with or without Ribavirin
Sequencing at a depth of ≥10% appears to be sufficient to predict HCV GT3 response to DCV+SOF±RBV. Expand
The HCV Treatment Revolution Continues: Resistance Considerations, Pangenotypic Efficacy, and Advances in Challenging Populations.
This article evaluates the data from clinical trials evaluating the safety and efficacy of direct-acting antivirals for the management of hepatitis C virus, and discusses recommendations from the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America guidance document. Expand
Discovery of Ruzasvir (MK-8408): A Potent, Pan-Genotype HCV NS5A Inhibitor with Optimized Activity against Common Resistance-Associated Polymorphisms.
The research that led to the discovery of compound 40 (ruzasvir, MK-8408), a pan-genotypic HCV nonstructural protein 5A (NS5A) inhibitor with a "flat" GT1 mutant profile, contains a unique tetracyclic indole core while maintaining the imidazole-proline-valine Moc motifs of previous NS5A inhibitors. Expand
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