The cyclophilin inhibitor Debio-025 shows potent anti–hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus

✍ Scribed by Robert Flisiak; Andrzej Horban; Philippe Gallay; Michael Bobardt; Suganya Selvarajah; Alicja Wiercinska-Drapalo; Ewa Siwak; Iwona Cielniak; Jozef Higersberger; Jarek Kierkus; Christian Aeschlimann; Pierre Grosgurin; Valérie Nicolas-Métral; Jean-Maurice Dumont; Hervé Porchet; Raf Crabbé; Pietro Scalfaro

• Book ID: 102849628
• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 522 KB
• Volume: 47
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.22131

✦ Synopsis

Debio-025 is an oral cyclophilin (Cyp) inhibitor with potent anti-hepatitis C virus activity in vitro. Its effect on viral load as well as its influence on intracellular Cyp levels was investigated in a randomized, double-blind, placebo-controlled study. Mean hepatitis C viral load decreased significantly by 3.6 log(10) after a 14-day oral treatment with 1200 mg twice daily (P < 0.0001) with an effect against the 3 genotypes (1, 3, and 4) represented in the study. In addition, the absence of viral rebound during treatment indicates that Debio-025 has a high barrier for the selection of resistance. In Debio-025-treated patients, cyclophilin B (CypB) levels in peripheral blood mononuclear cells decreased from 67 +/- 6 (standard error) ng/mg protein (baseline) to 5 +/- 1 ng/mg protein at day 15 (P < 0.01).

Conclusion:

Debio-025 induced a strong drop in cypb levels, coinciding with the decrease in hepatitis c viral load. these are the first preliminary human data supporting the hypothesis that cypb may play an important role in hepatitis c virus replication and that cyp inhibition is a valid target for the development of anti-hepatitis c drugs.