Debio-025 Activity/Safety in 3 Studies Over 3 Years

Debio-025 Activity/Safety in 3 Studies Over 3 Years

In naives, genotype 1 and 2:

1000 mg once daily produced slightly greater than 2 log reduction in HCV RNA after 29 days in genotype 1/4 and 4 logs in genotype 2/3 but at this dose 8/18 patients receiving monotherapy had hyperbilirubinemia but not at lower dose of 600 mg:

EASL 2008: Efficacy and safety of increasing doses of the cyclophilin ...
Debio 025 at daily doses of 1000 or 60 mg demonstrates an additive anti-HCV ... Debio 025in daily doses of 200 or 600 mg in combination with PegIFNa-2 was ...
www.natap.org/2008/EASL/EASL_20.htm

In this study 400 mg monotherapy did not produce antivial activity in null-responders, using a loading dose however showed better results suggested better antiviral activity, at these doses there did not appear to be hyperbilirubinemia:

EASL 2009: EFFICACY AND SAFETY OF THE CYCLOPHILIN INHIBITOR DEBIO 025 IN ...
EFFICACY AND SAFETY OF THE CYCLOPHILIN INHIBITOR DEBIO 025 IN COMBINATION WITH PEGYLATED INTERFERON ALPHA-2A AND RIBAVIRIN IN PREVIOUSLY NULL-RESPONDER ...
www.natap.org/2009/EASL/EASL_40.htm

The cyclophilin inhibitor DEBIO-025 has a potent dual anti-HIV and anti-HCV activity in treatment-naive HIV/HCV co-infected subjects


AASLD 2006: The cyclophilin inhibitor DEBIO-025 has a potent dual anti-HIV and ...
DEBIO-025, a cyclophilin inhibitor, demonstrated strong antiviral activity in vitro against HCV1 and HIV-1. In a previous phase I study, DEBIO-025 showed ...
www.natap.org/2006/AASLD/AASLD_30.htm
In a previous phase I study, DEBIO-025 showed antiviral effect (< 1 Log10 reduction) in HIV-1-positive asymptomatic subjects treated with DEBIO-025 400 and 1200 mg daily for 10 days2. In this early study presented at AASLD 2006, Treatment-naive HIV-1 mono or HIV/HCV co-infected subjects received 1200 mg DEBIO-025 or placebo twice daily for 15 days. HCV genotypes in the 16 HIV-1/HCV co-infected subjects on active treatment were evenly distributed between genotype 1 (n=5), genotype 3 (n=6), and genotype 4 (n=5). HIV-1/HCV co-infected DEBIO-025-treated subjects experienced a significantly greater maximum HCV viral load reduction compared to placebo subjects, achieving a least squares mean of 3.6 vs. 0.7. The 3 HCV genotypes identified in the study responded well to the dose administered (Figure 2). one null-responder (genotype 4) achieved at least a 2 Log10 drop in HCV viral load during treatment. Three subjects (one of each genotype) decreased viral loads below detectable levels at treatment Day 15 (2 subjects) and Day 8 (1 subject). Total bilirubin increased by a median of 22 _mol/L (range -1 to +88) during treatment, leading to hyperbilirubinaemia in 10 subjects. A total of 4/19 (21%) subjects discontinued DEBIO-025 treatment prematurely for this reason. No increase in ALT/AST or _-GT was observed, and there were no signs of haemolysis. Bilirubin returned rapidly to baseline levels after treatment cessation. This phenomenon was not observed in previous DEBIO-025 studies at doses up to 1200 mg OD for 10 days