title: An evaluation of the cyclophilin inhibitor Debio 025 and its potential as a treatment for chronic hepatitis C.
abstract: Debio 025 is a cyclophilin (Cyp) inhibitor without calcineurin-binding properties. The drug inhibits viral replication of genotype 1b and 2a replicons in nanomolar concentrations and shows an additive to synergistic antiviral effect with interferon, ribavirin, and specifically targeted antiviral therapy for hepatitis C (STAT-C) drugs. There is no cross-resistance with protease and polymerase inhibitors. In humans, Debio 025 has shown activity against genotypes 1, 2, 3, and 4, and displays an additive antiviral effect with pegylated interferon (peg-IFN)alpha2a in genotype 1 and 4 patients. The most prominent side effect is reversible hyperbilirubinaemia caused by inhibition of biliary transporters. Debio 025 is a potent anti-HCV drug, with a novel mechanism of action and an efficacy profile that makes it an attractive candidate for combination with current and future HCV treatments.
authors.affiliation: Debiopharm SA, Chemin Messidor 5-7, PO Box 5911, CH-1002 Lausanne, Switzerland. rcrabbe@debiopharm.com
authors.forename: Raf
authors.initials: R
authors.lastname: Crabbé
authors.forename: Grégoire
authors.initials: G
authors.lastname: Vuagniaux
authors.forename: Jean-Maurice
authors.initials: JM
authors.lastname: Dumont
authors.forename: Valérie
authors.initials: V
authors.lastname: Nicolas-Métral
authors.forename: Judith
authors.initials: J
authors.lastname: Marfurt
authors.forename: Laura
authors.initials: L
authors.lastname: Novaroli
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D021983:Cyclophilins / Q000037:antagonists & inhibitors*; D016572:Cyclosporine / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans
chemical_list: D000998:Antiviral Agents; D016572:Cyclosporine; D021983:Cyclophilins; C499715:alisporivir