Balapiravir plus peginterferon alfa-2a (40KD)/ribavirin in a randomized trial of hepatitis C genotype 1 patients(♦♦ Grant Support: This study was funded by Roche. The sponsor contributed to study design as well as data collection, analysis, and interpretation with input from the investigators. Writing support was provided by Blair Jarvis of Health Interactions and funded by Hoffman La-Roche Ltd. ClinicalTrials.gov Identifier: NCT00517439)

• Main Authors: David R. Nelson, Stefan Zeuzem, Pietro Andreone, Peter Ferenci, Robert Herring, Donald M. Jensen, Patrick Marcellin, Paul J. Pockros, Maribel Rodríguez-Torres, Lorenzo Rossaro, Vinod K. Rustgi, Thomas Sepe, Mark Sulkowski, Isaac R. Thomason, Eric M. Yoshida, Anna Chan, George Hill
• Format: Article
• Language: English
• Published: Elsevier 2012-01-01
• Series: Annals of Hepatology
• Subjects: Chronic hepatitis C; SVR; Safety
• Online Access: http://www.sciencedirect.com/science/article/pii/S1665268119314826

Introduction. Balapiravir (R1626, RG1626) is the prodrug of a nucleoside analogue inhibitor of the hepatitis C virus (HCV) RNA-dependent RNA polymerase (R1479, RG1479). This phase 2, double-blind international trial evaluated the optimal treatment regimen of balapiravir plus peginterferon alfa-2a (40KD)/ribavirin.Material and methods. Treatment-naive genotype 1 patients (N = 516) were randomized to one of seven treatment groups in which they received balapiravir 500, 1,000, or 1,500 mg twice daily, peginterferon alfa2a (40KD) 180 or 90 Mg/week and ribavirin 1,000/1,200 mg/day or peginterferon alfa-2a (40KD)/ribavirin. The planned treatment duration with balapiravir was reduced from 24 to 12 weeks due to safety concerns.Results. The percentage of patients with undetectable HCV RNA was consistently higher in all balapiravir groups from week 2 to 12. However, high rates of dose modifications and discontinuations of one/all study drugs compromised the efficacy assessment and resulted in similar sustained virological response rates in the balapiravir groups (range 32-50%) and the peginterferon alfa-2a (40KD)/ribavirin group (43%). Balapiravir was discontinued for safety reasons in 28-36% of patients (most often for lymphopenia) and the percentage of patients with serious adverse events (especially hematological, infection, ocular events) was dose related. Serious hematological adverse events (particularly neutropenia, lymphopenia) were more common in balapiravir recipients. Two deaths in the balapiravir/peginterferon alfa-2a/ribavirin combination groups were considered possibly related to study medication.Conclusion. Further development of balapiravir for the treatment of chronic hepatitis C has been halted because of the unacceptable benefit to risk ratio revealed in this study (www.ClinicalTrials.gov NCT 00517439).