Cenicriviroc placebo for the treatment of non-alcoholic steatohepatitis with liver fibrosis: Results from the Year 1 primary analysis of the Phase 2b CENTAUR study

Background & Aims:Chronic Hepatitis C (CHC), the leading cause of liver disease, infects more than 185 million people worldwide.The emergence of new molecules that act directly on the virus itself,such as anti-HCV polymerase Sofosbuvir, improved treatment regimens and outcomes. However, in addition to the extremely high cost of this therapy, there is also a risk of selecting viral escape mutants so a new combination is needed.Ideally, inhibitors should target different steps of the HCV infectious cycle, entry, replication, and assembly/ secretionandbe efficient against all HCV genotypes.Therefore, the development of novel, better-tolerated, and more-effective anti-HCV agents is urgently needed. The novel patented EHCV (Catvira)formulation composed of Sofosbuvir 400 mg / Ribavirin 1000 mg / Epigallocatechin Gallate 400 mg(EGCG) was developed. Catvira formulation incorporated EGCG for its anti-hemolytic and effective inhibitory activity against viral entry into human host cells.We evaluated the efficacy and safety ofa single daily fixed dose EHCV (Catvira) in comparison to the standard of care(Sofosbuvir 400 mg + Ribavirin 1000 mg)multiple tablets per day in CHC genotype 4 patients. Methods: Randomized open-label study to evaluate the efficacy and safety of Catvira for treating patients with CHC genotype 4 was carried out. Treatment-naïveandtreatment-experienced patientswith genotype 4 HCV infection (No. = 80) were randomly assigned to receive a single daily fixed dose EHCV (40 patients) or the standard of care Sofosbuvir + Ribavirin (40 patients) daily for 12 or 24 weeks. The trial has been registered at clinicaltrials.gov on June 19, 2015 at https://clinicaltrials.gov/ct2/show/NCT02483156?term=ehcv&rank=1 Results: SVR 12 and SVR 24 for EHCV (Catvira) showed no statistical significant difference when compared to the standard of care ( P < 0.1 & P < 0.2 respectively). Also EHCV (Catvira) demonstrated a much faster rate of viral load decline ( P < 0.01) which could be due to effective viral entry inhibition into human host cells by EGCG. Moreover EHCV (Catvira) did not affect RBCs count or Hemoglobin levels as compared to the standard of care that resulted in a significant decline ( P < 0.05) in both parameters after 24 weeks of treatment. This could be attributed to the anti-hemolytic effect of EGCG. Conclusion: Catvira, administered daily for 12 or 24 weeks, is safe and effective in both naïve and treatment experienced patients with genotype 4 HCV. Catvira’s anti-viral-entry mechanism may also play a role in enhancing effeciay over the standard of care. In addition to potentially ehanced efficacy, Catvira’s anti-hemolytic activity may improve the safety and tolerability of the therapy. Being a single daily dose of Catvira is another advantage leading to better compliance.