Lille (France), Cambridge (Massachusetts, United States), September 12, 2011 – GENFIT (Alternext: ALGFT;
ISIN: FR0004163111), a biopharmaceutical company at the forefront of drug discovery and development,
focusing on the early diagnosis and preventive treatment of cardiometabolic and associated disorders, today
announces important pre-clinical results supporting the development of GFT505 for the treatment of
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-1ß, TNFa, TGFß,
collagens) was totally blocked by GFT505.
- Another study highlights the role of activation of the nuclear receptor PPARd in the protective effect of
GFT505 (GFT505 is a dual PPARa/d agonist). In dyslipidemic mice with the gene for the nuclear
receptor PPARa inactivated (PPARa-KO) that were fed a high-fat diet to induce liver dysfunction,
GFT505 treatment prevented intra-hepatic triglyceride accumulation and reduced plasma levels of
ALAT. Accordingly, microscopic examination of the liver revealed the absence of steatosis and
inflammation in GFT505-treated mice. Once again, the expression of pro-inflammatory and pro-
fibrotic genes was strongly reduced by GFT505 treatment.
- 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.
Furthermore, upon reviewing the pre-clinical and clinical data, an internationally recognized NAFLD/NASH
specialist, Prof. Vlad Ratziu (MD-PhD, Hôpital Pitié-Salpêtrière, Pierre et Marie Curie University, Paris, France)
commented: “A drug like GFT505, which systematically improves insulin resistance and lipid flux through the
liver (by reducing free fatty acid delivery and increasing free fatty acid oxidation), that reduces the expression
of inflammatory mediators, and reduces fibrogenesis in the liver would be, indeed, an ideal molecule for
GENFIT is a biopharmaceutical company focused on the Discovery and Development of drug candidates in
therapeutic fields linked to cardiometabolic disorders (prediabetes/diabetes, atherosclerosis, dyslipidemia,
inflammatory diseases…). GENFIT uses a multi-pronged approach based on early diagnosis, preventive
solutions, and therapeutic treatments and advances therapeutic research programs, either independently or in
partnership with leading pharmaceutical companies (SANOFI, SERVIER, …), to address these major public health
concerns and their unmet medical needs.
GENFIT’s research programs have resulted in the creation of a rich and diversified pipeline of drug candidates
at different stages of development, including GENFIT’s lead proprietary compound, GFT505, that is currently in
With facilities in Lille, France, and Cambridge, MA (USA), the Company has approximately 100 employees.
GENFIT is a public company listed on the Alternext trading market by Euronext™ Paris (Alternext: ALGFT; ISIN:
Jean-François Mouney – CEO & Chairman of the Management Board
+33 (0)3 2016 4000
MILESTONES – Press Relations
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