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 J 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 G.Mohan 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 J Thompson and Jos{\'e} Luis Calleja Panero and S. Ferret and Luis Margusino Franinan and Maria Angeles Castro Iglesias and Ashley S. Brown and Kaushik Agarwal and Graham Foster and Matthew E. Cramp and Eli Zuckerman and E Veitsman and Michal Becker 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… 
5 Citations
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.
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.
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.
Curing Hepatitis C with Direct‐Acting Antiviral Therapy
  • M. Sofia
  • Medicine
    New Drug Development for Known and Emerging Viruses
  • 2021


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.
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.
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.
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.
The following authors have nothing to disclose
  • Education
    American Journal of Infection Control
  • 2018
Eliav Barr and Heather Platt are employees of Merck Sharp & Dohme Corp
    We extend our gratitude to the participants, their families, investigators and site personnel who participated in these studies. The C-BREEZE-2 Study Investigators were as follows
      Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C