Cyclophilin inhibitors

Abstract

Cyclophilin (Cyp) inhibitors are host targeting antivirals binding proteins essential for hepatitis C virus (HCV) replication. The first known Cyp inhibitor-cyclosporine Awas able to enhance anti-viral effect of interferon alfa (IFNalfa) plus ribavirin (RBV), but because of contrary immunosuppressive properties was insufficient to support use in HCV infected patients. Preclinical studies using nonimmunosuppressive Cyp inhibitors, Debio 025, NIM811 and SCY-635 demonstrated potent anti-HCV effect. The most advanced in clinical trial Debio 025 (Alisporivir, ALV) is studied in ongoing phase 3 clinical trial. Phase 1 and 2 studies confirmed that addition of ALV to PegIFN-alfa and RBV in HCV genotype 1 infected improved sustained viral response rate up to 75%. Ongoing studies are expected to support efficacy of interferon-free regimen containing ALV in genotype 2/3 infected patients, improvement of efficacy in nonresponders to previous standard therapy and possible rescue therapy after failure of direct acting antivirals. © 2012 Springer Science+Business Media, LLC.