Debio 025 is a selective cylophilin inhibitor that has previously demonstrated antiviral activity against hepatitis C virus in both laboratory studies and early clinical trials. It has also exhibited activity against HIV.

At the recent 43rd annual meeting of the European Association for the Study of the Liver (EASL) last month in Milan, researchers described the latest data from a Phase II study of Debio 025 in combination with pegylated interferon in chronic hepatitis C patients.

The study included 90 participants randomly allocated (n=12 per arm) to receive one of the following treatment regimens for 29 days:

• 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus placebo;

• pegylated interferon plus 200 mg/day Debio 025;

• pegylated interferon plus 600 mg/day Debio 025;

• pegylated interferon plus 1000 mg/day Debio 025;

• 1000 mg/day Debio 025 monotherapy.

Results

In an intent-to-treat analysis, among patients with HCV genotypes 1 or 4, reductions in HCV RNA at day 29 were as follows:

• Pegylated interferon plus 1000 mg Debio 025: 4.75 log10 IU/mL;

• Pegylated interferon plus 600 mg Debio 025: 4.61 log10 IU/mL;

• Pegylated interferon plus placebo: 2.49 log10 IU/mL;

• Debio 025 1000 mg monotherapy: 2.20 log10 IU/mL;

• Pegylated interferon plus 200 mg Debio 025: 1.8 log10 IU/mL;

• 8 of 12 patients (67%) in the pegylated interferon plus 1000 mg Debio 025 arm had undetectable viral load (< 15 IU/mL) at day 29, compared with 3 of 12 patients (25%) in both the pegylated interferon plus placebo and the Debio 025 monotherapy arms.

• Among genotype 2 or 3 patients, 4 out of 6 (67%) achieved undetectable HCV RNA with Debio 025 monotherapy.

• The mean reduction of HCV RNA in this group was 4.22 log10 IU/mL.

• At lower doses, the safety profile of Debio 025 was comparable to that of placebo.

• 5 of 24 patients (21%) receiving 1000 mg Debio 025 developed reversible increases in conjugated bilirubin resulting in hyperbilirubinemia (total bilirubin > 3 mg/dL; range 3.1-8.1).

Based on these findings, the researchers concluded, "Debio 025 at doses of 600 and 1000 mg daily for 29 days shows an important additive anti-HCV effect when co-administered with pegylated interferon alpha-2a in treatment-naive HCV patients."

Department of Infectious Diseases, Medical University, Bialystok, Poland; Mount Sinai Hospital, Toronto, Canada; Clinic for Infectious Diseases, Medical University, Lodz, Poland; Hospital for Infectious Diseases, Warsaw, Poland; Department of Infectious Diseases, Regional Hospital, Kielce, Poland; Department of Infectious Diseases, Medical University, Bydgoszcz, Poland; Department of Medicine, University of Toronto, Toronto, Canada; Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy; Department of Medicine, University of Modena and Reggio Emilia, Modena, Italy; Debiopharm SA, Lausanne, Switzerland.

About Debiopharm Group

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5/06/08

Reference
R Flisiak, SV Feinman, M Jablkowski, and others. Efficacy and Safety of Increasing Doses of the Cyclophilin Inhibitor Debio 025 in Combination with Pegylated Interferon Alpha-2a in Treatment Naive Chronic HCV Patients. 43rd Annual Meeting of the European Association for the Study of the Liver (EASL 2008). Milan, Italy. April 23-27, 2008.

Additional Source
Debiopharm Group. Clinical Update - Debio 025 in Hepatitis C -- Presentation of Phase IIa Efficacy Results. Press release. April 28, 2008.