Resmetirom: the first approved therapy for treating metabolic dysfunction associated steatohepatitis

Abstract

Introduction: Metabolic dysfunction associated steatohepatitis (MASH), previously referred to as nonalcoholic steatohepatitis (NASH), has emerged as one of the leading indications for liver transplantation in the United States. The disease is associated with increased cardiovascular mortality in patients with early-stage liver fibrosis and a heightened risk of hepatic complications in those with advanced fibrosis. Despite its growing prevalence and significant healthcare burden, there were no approved drugs to treat this chronic disease. In March 2024, Resmetirom, a selective thyroid hormone receptor-beta agonist, became the first drug to receive FDA approval for the treatment of patients with MASH and fibrosis stages F2/F3. This accelerated approval was granted based on significantly higher rates of MASH resolution and fibrosis.

Areas covered: This review summarizes the current literature on the mechanism of action, preclinical data, pharmacokinetics, clinical efficacy, indications, and contraindications of resmetirom in the management of patients with MASH.

Expert opinion: The approval of resmetirom for patients with MASH and moderate to advanced hepatic fibrosis is a major advance in the management of MASH. The recent positive results of the ESSENCE trial of semaglutide, if associated with conditional approval, may offer clinicians two options to treat MASH in patients with moderate to advanced fibrosis.

Keywords: MASLD; NAFLD; Resmetirom; emerging therapy; future.