Metabolic liver diseases are becoming a major public health issue worldwide. They are closely linked to the development of type 2 diabetes and obesity in the population.
NAFL (non-alcoholic fatty liver), is characterized by the accumulation of triglycerides in the liver. It is a risk condition that can develop into NASH (non-alcoholic steatohepatitis). This disease strongly increases the risk of cirrhosis and hepatocellular carcinoma and has very low survival rates.
According to the World Gastroenterology Organization, the prevalence of NAFL and NASH has doubled in the last 20 years. Today, NAFL affects 20 to 26% of the population in Europe and 20 to 46% of the population in the United States.
There is currently no therapeutic or preventive treatment with proven efficacy available for these hepatic disorders.
Sources: World Gastroenterology Organization Global Guidelines,
Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis, 2012;
Younossi et al. Hepatology, 2016;
Williams et al., Gastroenterology, 2011.
chance of surviving 10 years: this is the current prognosis for patients with NASH.
Source: WGO Guidelines, 2012.
of patients presenting with non alcoholic fatty liver (NAFL) will develop NASH. Therefore it is referred to as a risk condition for contracting NASH.
Source: Williams et al., Gastroenterology, 2011.
Beyond prediabetes, VALEDIA® is specifically developed in the field of non alcoholic fatty liver diseases (NAFLDs), for the risk reduction of NASH. This complementary indication is supported by promising results on hepatic steatosis and a mechanism of action on several key targets of the pathophysiology of NAFLDs.
The purpose of VALEDIA® is to significantly reduce non alcoholic fatty liver and to prevent the inflammation and degeneration of hepatic cells which lead to the development of NASH.
The studies conducted on NAFLDs preclinical models repeatedly demonstrated the efficacy of TOTUM-63, active ingredient of VALEDIA® on hepatic steatosis:
These preliminary efficacy data validates VALEDIA® as a product with great preventive potential in NAFLDs.
TOTUM-63 was the subject of a Phase I/II study completed in June 2017. This study validated the safety and tolerance of this active ingredient from a clinical perspective.
Furthermore, this Phase I/II study also confirmed significant improvement in insulin sensitivity and significant reduction in blood triglycerides and total cholesterol levels. Insulin resistance and dyslipidemia are known to have a strong link with the development of fatty liver disease.
Mechanism of action studies revealed a significant increase in gene expression of Ppar ß/∂ and FXR by TOTUM-63, both key transcription factors of the hepatic energy metabolism. Simultaneously, the active ingredient of VALEDIA® almost completely inhibited the expression of the protein Fsp27, which regulates lipid storage and is specifically expressed in steatotic livers.
This mechanism of action, which targets the control of the hepatic metabolism, represents a major asset in reducing the risk of NASH.
VALEDIA® will be tested in a Phase II clinical study on the target population, to demonstrate its efficacy in reducing non alcoholic fatty liver in patients at risk of developing NASH. Steatosis and its evolution will be measured by a non-invasive method.