Vonafexor (EYP001): A Comprehensive Analysis of a Differentiated FXR Agonist Targeting the Hepato-Renal Axis

Executive Summary

Vonafexor (EYP001) is an investigational, orally administered, small molecule drug representing a new generation of therapy targeting the Farnesoid X Receptor (FXR). Developed by the French biopharmaceutical company ENYO Pharma, Vonafexor is distinguished by its unique pharmacological profile as a highly selective, non-steroidal, non-bile acid FXR agonist. This structural and functional differentiation from earlier agents in its class forms the basis of a therapeutic hypothesis centered on maximizing efficacy while mitigating the challenging side effects that have hindered the development of other FXR-targeted therapies.

The clinical development of Vonafexor has been marked by a pivotal strategic evolution, informed by compelling clinical data. The Phase IIa LIVIFY trial, initially designed to evaluate the drug's efficacy in patients with fibrotic Metabolic dysfunction-associated steatohepatitis (MASH), successfully met its primary and secondary hepatic endpoints. It demonstrated significant reductions in liver fat content, liver enzymes, and markers of fibro-inflammation. However, the trial's most consequential finding was an unprecedented improvement in renal function, as measured by estimated glomerular filtration rate (eGFR), a benefit not previously observed with any other FXR agonist in this patient population.