Cyclophilin Inhibitors

Cyclophilin (Cyp) inhibitors are host targeting antivirals binding proteins essential for hepatitis C virus (HCV) replication. The first known Cyp inhibitor–cyclosporin A was able to enhance anti-viral effect of interferon alfa (IFN-alfa) plus ribavirin (RBV), but because of contrary immunosuppressive properties was insufficient to support use in HCV infected patients. Preclinical studies using non-immunosuppressive 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 non-responders to previous standard therapy and possible rescue therapy after failure of direct acting antivirals.