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Clinical Trials

Date: 2011-09-12

Type of information: Results

phase: preclinical

Announcement: results

Company: Genfit (France)

Product: GFT505

Action mechanism: PPAR agonist. Elafibranor (GFT505) is an oral once-daily treatment, and a first-in-class drug acting via dual peroxisome proliferator-activated alpha/delta pathways to treat nonalcoholic steatohepatitis (NASH).

Disease:

NASH (non-alcoholic steatohepatitis

NAFLD (non-alcoholic fatty liver disease)

Therapeutic area: Liver diseases - Metabolic diseases

Country:

Trial details:

Latest news:

Genfit has announced important pre-clinical results supporting the development of GFT505 for the treatment of NAFLD/NASH. In parallel with the epidemic prevalence of diabetes and obesity, there is currently a sharp increase in the incidence of non-alcoholic fatty liver disease (NAFLD). Indeed, NAFLD occurs in 80-100% of diabetic patients, and can progress to chronic liver disease (NASH) in 20-50% of cases. Subsequently, NASH can progress to cirrhosis and even liver cancer. Mortality linked to liver disease is thus 2-3 times higher in a diabetic population compared to a non-diabetic population. There is currently no approved treatment for NASH, and the late stage development pipeline for this disease is very weak. Thus, considering this unmet medical need and its increasing worldwide prevalence, a recent GlobalData analysis stated that any drug with proven efficacy on NAFLD/NASH (reduction in liver steatosis, inflammation, and fibrosis) which has a favorable safety profile could rapidly become a blockbuster. In this context, a series of studies recently performed by GENFIT have demonstrated the efficacy of GFT505 in various pre-clinical models of NAFLD/NASH: - In a recognized model of NAFLD/NASH (Methionine-Choline Deficient Diet for 6 weeks in normal or diabetic mice), microscopic examination of the liver showed that GFT505 oral treatment prevented the inflammation and accumulation of fat (steatosis) induced by the diet. GFT505 treatment also strongly reduced plasma concentrations of ALAT, a marker of liver dysfunction. Furthermore, the diet-induced increased liver expression of pro-inflammatory and pro-fibrotic genes (IL-1Beta, TNFalpha, TGFBet, collagens) was totally blocked by GFT505. - Another study highlights the role of activation of the nuclear receptor PPAR in the protective effect of GFT505 (GFT505 is a dual PPARalpha/delta agonist). - In a rat model of hepatic fibrosis (ip injections of CCl4), GFT505 totally prevented the development of liver fibrosis as determined by histological examination. This correlated with reduced expression of pro-inflammatory and pro-fibrotic genes.

Finally, the different studies performed to date demonstrate that after oral administration of GFT505, this drug candidate mainly targets the liver. These data further confirm the conclusions of a committee of independent international experts that recently examined the clinical results of GFT505, and that already strongly recommended pursuing its development on cardiovascular protection in high-risk patients, and particularly for NAFLD/NASH.

Is general: Yes