From Basic Liver Research to NASH drug therapy

Centre for Cooperative Research in Biosciences (CIC bioGUNE)

Non-alcoholic steatohepatitis (NASH) is fatty liver disease, characterized by inflammation and fat accumulation in the liver, due to causes other than alcohol. Some studies suggest that actions like undergoing a diet, doing exercise, or using antiglycemic drugs could improve the course of the disease, but the approval of a specific, effective drug for NASH has remained a pending issue.


A new drug against NASH

Galmed Pharmaceuticals announced in June 2018 that their lead Non-alcoholic Steatohepatitis (NASH) drug candidate, Aramchol, had achieved a FDA- regulatory-approvable endpoint demonstrating NASH resolution in the Aramchol Phase 2b, 52-week ARREST trial.

Aramchol is a conjugate of cholic acid and arachidic acid, a first-in-class member of a novel family of synthetic Fatty-Acid/Bile-Acid Conjugates (FABACs). These positive results meant that the new drug was on track for Phase III initiation and further clinical evaluation of its efficacy in NASH.

Some therapeutic approaches exist, but no dedicated, efficient drug for NASH has been available since its discovery in the 90s.

Pre-clinical studies on Aramchol were carried out at the AAALAC-certified animal facility from the Severo Ochoa Excellence research center CIC bioGUNE, led by General Director Prof. José Mª Mato and Prof. Juan Anguita. Professor Mato had described in a recent publication in collaboration with OWL Metabolomics that Aramchol exhibits a specific mechanism-of-action that targets both the metabolic alterations characterizing NASH-accumulation of lipids, lipotoxicity and oxidative stress as well as liver fibrosis.

Aramchol’s unique dual mechanism-of-action was first evaluated by a joint CIC bioGUNE / OWL Metabolomics research teams together with Galmed Pharmaceuticals and then further validated in patients with biopsy verified NASH within the latest ARREST trial Phase 2b update.  This scientific collaboration is a very good example of how knowledge generated in basic research can be transferred to ongoing research in the pharma industry. Knowledge transfers from the academic setting to industry with the ultimate goal of providing NASH patients with effective therapies.


About NASH, fatty liver

NASH is a clinically-relevant progressed form of non-alcoholic fatty liver disease (NAFLD), and is histologically defined as the presence of fat (steatosis) together with inflammation and hepatic damage. NASH can evolve to major hepatic damage, advanced fibrosis, cirrhosis and hepatocellular carcinoma (HCC). In the last few decades, the incidence of NAFLD has expanded rapidly and is currently the leading cause of chronic liver disease with a prevalence ranging between 10 and 40% in the adult population of Western countries, which progress to NASH in approximately 10-30% of the cases.

NASH is a serious liver condition leading to manifold negative consequences.

In the USA, NASH is currently the second leading cause of liver transplant, and it has been estimated that it will be the first cause in the foreseeable future. Currently, there is no approved drug for NASH and treatments are aimed to control the associated comorbidities such as obesity, diabetes and hyperlipidemia. Today, the definitive diagnosis of NASH depends on performing an invasive liver biopsy, a medical procedure with some controversies due to the variability in sampling variation, inter-observer variability, high cost and patient safety risks.  This is one reason many current NASH patients are not appropriately diagnosed.


Image credits

Pills picture was downloaded from Flickr and licensed via a Creative Commons Attribution 2.0 Generic (CC BY 2.0) license.

Liver drawing is in the public domain and was downloaded from Pixabay.