Date: 2014-03-19
Type of information: Preclinical data
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). Elafibranor is believed to address mutliple facets of NASH, including inflammation, insulin sensitivity, lipid/metabolic profile, and liver markers.
Disease: NASH (non-alcoholic steatohepatitis)
Therapeutic area: Metabolic diseases - Liver diseases
Country:
Trial details:
Latest
news: • On March 19, 2014, Genfit has anounced new data from Professor Isabelle Leclercq of Université Catholique de Louvain (Belgium) demonstrating the curative effects of GFT505 in an experimental model of NASH associated with metabolic disorders. The NASH model used in this study (foz/foz mice subjected to a high-fat diet) accurately reproduces the natural evolution of the disease in man. Thus, several metabolic disorders (obesity, insulin resistance, diabetes, dyslipidemia) lead to the establishment of NASH (steatosis with inflammation and hepatocyte ballooning) and the progressive development of hepatic fibrosis.
The experimental protocol therefore reproduces the ongoing Phase IIb clinical study (GFT505-212-7). After a period of establishment of the disease by a high-fat diet, the animals were as expected obese, insulin resistant, and dyslipidemic, and had NASH associated with hepatic fibrosis upon microscopic examination of the liver.
These animals with established NASH (average NAS score of 5) were then maintained on the high-fat diet for a further 18 weeks, one group under GFT505 treatment and one group under placebo. The results show that GFT505 eliminates NASH and improves fibrosis. Thus, there was almost no NASH remaining in the group treated with GFT505, while the pathology continued to develop in the placebo group. The three major NASH parameters (steatosis, ballooning, and inflammation) all improved in parallel. More importantly, the animals treated with GFT505 were almost free of fibrosis. Finally, compared to the placebo group, the mice treated with GFT505 showed a significant weight loss in spite of unchanged food intake, and an improvement in diabetes parameters and plasma lipids.
The full results of the study will be presented at the American Association for the Study of Liver Diseases (AASLD) congress to be held in Boston in November 2014.
