Resmetirom, the first FDA-approved drug for MASH: From drug discovery and action mechanisms to clinical trials.

Metabolically-dysfunction-associated steatohepatitis (MASH) represents one spectrum of MASLD, affecting over 5.27% of adults globally. Until the approval of resmetirom, no pharmacological therapies were available for MASH. Resmetirom is prescribed for the management of non-cirrhotic MASH in adults with moderate to advanced hepatic fibrosis, specifically at Stages F2 to F3. This drug is uniquely transported via liver-targeted transporters and exerts its effects by closely replicating the physiological actions of T3 (FT3). It exhibits a 28-fold selectivity for the thyroid hormone receptor beta (THR-β), predominant in the liver, over THR-α in functional assays. The approval of resmetirom marks a significant milestone, addressing a critical unmet need in MASH treatment while initiating a new chapter in therapeutic strategies for this complex chronic liver disease.