Non-Invasive Tests: Establishing efficacy for metabolic dysfunction associated steatohepatitis beyond the biopsy—current perspectives from the division of hepatology and nutrition, US Food and Drug Administration

Abstract

To support drug development for metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis, multiple stakeholders including patients, clinicians, and investigators have communicated a desire to move away from liver histology. FDA accelerated approval is based on a surrogate endpoint (such as liver histology) that has less definitive evidence tying it to the clinical endpoint (such as death or liver transplant) but nonetheless is considered reasonably likely to predict clinical benefit -- a reasonably likely surrogate endpoint (RLSE). This communication is intended to provide some of the regulatory considerations on adopting non-invasive tests in lieu of liver histology as a RLSE in drug development for MASH. We will also describe FDA mechanisms and the methods by which data can be submitted to the FDA to consider proposals for NIT use in place of liver histology as RLSEs.