Resmetirom for the treatment of nonalcoholic steatohepatitis: Evaluating the robustness of available evidence

Non-alcoholic steatohepatitis (NASH), recently renamed metabolic dysfunction-associated steatohepatitis (MASH) [ [1] Rinella M.E. Lazarus J.V. Ratziu V. et al. A multi-society Delphi consensus statement on new fatty liver disease nomenclature. Ann Hepatol. 2023; 101133 PubMed Google Scholar ] is still an orphan condition, with no pharmacological therapy yet approved for use in clinical practice. Nonetheless, the clinical trial landscape in the field is rapidly changing with several molecules currently being studied in Phase 3 clinical programs. In particular, thyroid hormone beta receptor (TRB) agonists have received considerable attention as they reduce de novo lipogenesis, promote fatty acid oxidation, modulate mitophagy and mitochondrial biogenesis as well as cholesterol metabolism and potentially exert direct anti-inflammatory and anti-fibrotic effects. Among them, resmetirom in further along the clinical development program and is currently being evaluated for potential approval by the US Food and Drug Administration [ [2] Harrison S.A. Ratziu V. Anstee Q.M. et al. Design of the phase 3 MAESTRO clinical program to evaluate resmetirom for the treatment of nonalcoholic steatohepatitis. Aliment Pharmacol Ther. 2024; Crossref Scopus (4) Google Scholar ]. In particular, the ongoing Phase 3 MAESTRO clinical program is evaluating efficacy and safety in both patients with at-risk NASH and in patients with NASH cirrhosis [ [2] Harrison S.A. Ratziu V. Anstee Q.M. et al. Design of the phase 3 MAESTRO clinical program to evaluate resmetirom for the treatment of nonalcoholic steatohepatitis. Aliment Pharmacol Ther. 2024; Crossref Scopus (4) Google Scholar ].