Update on  alisporivir  in treatment of viral hepatitis C.
BACKGROUND
There are two classes of anti-hepatitis C virus (HCV) agents currently in development: direct-acting antivirals (DAA) and host-targeting antivirals (HTA). Cyclophilin inhibitor alisporivir (ALV) , previously known as Debio-025 is the most advanced HTA in development.


METHODS
Experimental and clinical studies demonstrated that ALV has high genetic barrier and no cross-resistance to DAA. Pharmacokinetic studies showed a profile suitable for once-daily administration. Phase I and II studies confirmed strong HCV suppression and that addition of ALV to pegylated IFNα (PegIFNα) and ribavirin (RBV) can improve their efficacy significantly. ALV was well tolerated and prevalence of the most frequent clinical and laboratory adverse events was similar to PegIFNα/RBV. Hyperbilirubinemia was the only significant adverse event related to ALV, but it was transient, reversible and not associated with hepatotoxicity or cholestasis.


CONCLUSIONS
ALV is pangenotypic, with once-daily administration and safe, therefore medication can be easy and flexible. There is still a need of data in difficult-to-treat populations and genetic studies allowing selection of possible non-responders. Registration of ALV for IFN-based treatment is expected within 3 years, but ALV is also a good candidate for IFN-sparing combinations with DAA.
Medical University of Białystok, ul. Żurawia 14, Białystok, Poland. robert.flisiak@umwb.edu.pl
Robert
R
Flisiak
Jerzy
J
Jaroszewicz
Iwona
I
Flisiak
Tadeusz
T
Łapiński
D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D021983:Cyclophilins / Q000037:antagonists & inhibitors; D016572:Cyclosporine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D015195:Drug Design; D024882:Drug Resistance, Viral; D016174:Hepacivirus / Q000187:drug effects; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans
D000998:Antiviral Agents; D016572:Cyclosporine; D021983:Cyclophilins; C499715:alisporivir