Resmetirom, also known as MGL-3196, is a selective THR-β agonist developed as a liver-directed therapy. FDA identifies MGL-3196 as the active substance associated with Rezdiffra.
Pharmacology
THR-β activation influences hepatic lipid metabolism. Resmetirom was designed to preferentially activate this receptor and produce liver-directed metabolic effects.
Pharmacokinetics
The current FDA prescribing information contains detailed information concerning absorption, distribution, metabolism, elimination and pharmacodynamic effects. The exact pharmacokinetic parameters should be taken from the latest official label rather than extrapolated from earlier investigational formulations.
Clinical evidence
The MAESTRO-NASH program provided important evidence supporting approval. FDA’s original approval relied on a clinical trial involving 888 adults with biopsy-confirmed NASH and moderate or advanced fibrosis without cirrhosis.
The pivotal phase 3 study was published in the New England Journal of Medicine in 2024.
EMA reports that, in its main study, approximately 26–30% of Rezdiffra-treated participants achieved MASH resolution without worsening fibrosis compared with approximately 10% receiving placebo, while approximately 27–29% experienced fibrosis improvement without worsening of MASH compared with 17% receiving placebo.
Evidence limitations
The U.S. approval remains under accelerated approval. A confirmatory study is required to verify clinical benefit on outcomes including progression to cirrhosis, hepatic decompensation, transplantation and mortality.
Ongoing research
ClinicalTrials.gov records ongoing studies examining resmetirom in additional populations, including well-compensated NASH cirrhosis. Such research does not establish an approved indication.