Genfit's Advanced Compound Status

GFT505:  A Phase II drug candidate for the prevention and treatment of micro- and macrovascular risk in prediabetic and diabetic patients

GFT505 is Genfit’s most advanced drug candidate in clinical development for the treatment of diabetic and dyslipidemic patients.

GFT505 belongs to a new generation of drug candidates stemming directly from Genfit’s research and developed in-house up to Phase II clinical trials.

Originating from Genfit’s Selective Nuclear Receptor Modulator (SNuRM) platform that was set up to identify innovative drug candidates that are more effective and safer than current therapies, GFT505 is currently developed as a once-daily oral formulation for atherogenic dyslipidemia associated with prediabetes and diabetes.

Through its unique activity profile, GFT505 works simultaneously on several risk factors associated with prediabetes and diabetes: the lipid triad (LDL- and HDL-cholesterol  and triglycerides) and inflammation. Furthermore, in preclinical studies, it showed efficacy on insulin resistance, diabetes, and atherosclerosis.

In all the clinical studies conducted to date, GFT505 demonstrates an excellent efficacy/safety ratio.For example, in a study conducted for 14 days in healthy volunteers, GFT505 showed significant effects on plasma lipids from 60 mg/day and confirmed its excellent tolerance as, up to 100 mg/day, no treatment-related side effects or any notable effects on plasmatic safety markers were reported.

  

In detail:

GFT505 demonstrated its excellent safety profile in Phase I double-blind trials vs. placebo with a daily administration of increasing doses up to 100 mg/day, for 14 days. In addition to the lack of treatment-related adverse events, GFT505 up to the strongest dose did not show any effect on hematocrit, red blood cell number, hemoglobin, and creatinine. Homocysteine levels also remained normal in the group treated with GFT505.

In this study, GFT505 showed strong effects on plasma lipids: after 14 days of treatment, GFT505 significantly reduced the level of triglycerides, in a dose-dependent manner. At a dose of 60 mg/day, a reduction of 35% was obtained vs. placebo (p<0.05). The reduction reached 45% vs. placebo (p<0.01) at a dose of 100 mg/day. In parallel, an 11% increase of plasma HDL-cholesterol was measured vs. placebo (p=0.07) in the 100 mg/day group. 

GFT505 has also demonstrated its therapeutic potential on dyslipidemic patients. In the first Phase IIa clinical trial conducted over 28 days with 30 mg/day GFT505 vs. placebo on a limited number of  patients with type 2b dyslipidemia, GFT505 showed a broad activity profile, reducing levels of triglycerides, non HDL-cholesterol, and remnant particles. In addition, the levels of ApoCIII, ApoB and ApoE (the apolipoproteins of VLDL and LDL particles) were reduced and the levels of HDL-cholesterol, ApoAI and ApoAII were increased. Finally, a reduction of plasma fibrinogen levels was observed. General tolerance was excellent, with no adverse effect recorded among the patients treated with GFT505.

Two larger Phase IIa trials have also been launched, to confirm and complete these encouraging results.

A Phase IIa trial is currently being conducted to evaluate the effect of 80 mg/day GFT505 vs. placebo on patients with abdominal obesity and atherogenic dyslipidemia (TG>150 mg/dL, HDL-C<40 mg/dL for men or <45 mg/dL for women). A second trial is being conducted in patients with impaired glucose tolerance and abdominal obesity. Results are expected before the end of 2009.

In conclusion, due to its activity on a number of disorders associated with prediabetes and diabetes, GFT505 is well positioned for the prevention & treatment of micro- and macrovascular risk in prediabetic and diabetic patients.