Elafibranor: a potential drug for the treatment of nonalcoholic steatohepatitis (NASH)

Introduction: Nonalcoholic fatty liver disease (NAFLD) encompasses a progressive disease phenotype starting from simple steatosis, which can progress to nonalcoholic steatohepatitis (NASH). It is component of the metabolic syndrome with a large impact on mortality in these patients. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate lipid and insulin metabolism, two key components in pathophysiology of NAFLD and NASH. Elafibranor acts as an agonist of PPAR-alpha and PPAR-delta and is currently under development for the treatment of NAFLD. Areas covered: This review summarizes the pharmacological aspects, the preclinical and clinical effectivity, and safety data of elafibranor for the treatment of nonalcoholic steatohepatitis and fibrosis. Expert opinion: Current data support an effect of elafibranor on the resolution on NASH and the improvement of two key drivers of NASH progression - insulin resistance and serum lipid normalization. The safety profile is favorable, though reversible serum creatinine elevations occur with use, potentially limiting its use in patients with concurrent renal disease. The modest effect sizes in different NAFLD disease stages of elafibranor and other drugs in development for NASH, will likely lead to pursuing of drug combinations personalized to each stage of the NAFLD disease spectrum.