Comprehensive Report on MGL-3196 (Resmetirom/Rezdiffra): A Novel Thyroid Hormone Receptor-Beta Agonist

1. Executive Summary

MGL-3196, now known by the generic name Resmetirom and marketed as Rezdiffra, is a first-in-class, orally administered, once-daily, liver-directed, selective thyroid hormone receptor-beta (THR-β) agonist.[1] It has recently achieved a significant regulatory milestone with accelerated approval from the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with noncirrhotic non-alcoholic steatohepatitis (NASH) characterized by moderate to advanced liver fibrosis (stages F2 to F3), to be used in conjunction with diet and exercise.[4] This approval addresses a critical unmet medical need, as NASH is a prevalent and progressive liver disease that previously lacked any FDA-approved pharmacological therapies.[5]

The clinical development program for Resmetirom, notably the MAESTRO-NASH trial, has provided evidence of its efficacy in achieving key histological endpoints, including NASH resolution without worsening of fibrosis and improvement in fibrosis stage by at least one stage without worsening of NASH, at 52 weeks of treatment.[7] Beyond its direct effects on liver histology, Resmetirom has also demonstrated beneficial effects on atherogenic lipid profiles. Significant reductions in low-density lipoprotein cholesterol (LDL-C), triglycerides, and other atherogenic lipoproteins have been observed in NASH clinical trials and further substantiated in trials conducted in patients with Heterozygous Familial Hypercholesterolemia (HeFH).[10]