Nonalcoholic steatohepatitis (NASH) is a liver disease that can lead to cirrhosis and liver cancer, and there is currently no effective drug therapy available for its treatment.

The farnesoid X receptor (FXR) has emerged as a promising therapeutic target for liver disorders such as NASH. However, the most advanced FXR agonist in clinical development, obeticholic acid (OCA), has shown therapy-limiting side effects.

Other FXR agonists such as cilofexor and tropifexor have also exhibited some adverse effects. Nidufexor, an FXR partial agonist, has shown efficacy in reducing liver fat content and ALT levels in NASH rodent models and in a phase II trial in patients with NASH.

EW-8198 is an intestine-specific FXR partial agonist that showed improved activity compared to its predecessor.

Studies in rats showed that a significant amount of the drug was absorbed in the intestine after oral administration and was rapidly metabolized to an inactive form by serum esterases after entering the portal vein.

EW-8198 reduced liver fibrogenesis markers and proinflammatory cytokines without affecting serum cholesterol levels, making it a potential candidate for NASH treatment with limited undesirable side effects. .