Rezdiffra Mechanism of Action
Rezdiffra (resmetirom) is an oral thyroid hormone receptor-beta (THR-β) agonist that selectively targets hepatic metabolic pathways to reduce liver fat and fibrosis in patients with metabolic dysfunction-associated steatohepatitis (MASH). 1
Primary Mechanism
Resmetirom functions as a selective thyroid hormone receptor-beta agonist, binding preferentially to THR-β receptors which are highly expressed in the liver 1
The drug targets the key underlying causes of MASH by modulating hepatic lipid metabolism through thyroid hormone receptor activation 1
Therapeutic Target and Selectivity
THR-β selectivity is critical to the mechanism, as this receptor subtype predominates in hepatic tissue, allowing targeted metabolic effects in the liver while minimizing systemic thyroid hormone effects 1
By activating THR-β receptors, resmetirom enhances hepatic fatty acid oxidation and reduces hepatic lipogenesis, addressing the fundamental metabolic dysfunction that drives steatohepatitis 1
Clinical Application
Resmetirom received FDA accelerated approval in March 2024 for use in conjunction with diet and exercise for treating adults with noncirrhotic MASH with moderate to advanced liver fibrosis (stages F2 to F3) 1
The oral formulation allows convenient once-daily dosing, making it practical for chronic management of this progressive liver disease 1
Distinguishing Features
Unlike nonspecific thyroid hormone replacement, the THR-β selectivity avoids many systemic thyroid effects such as cardiac stimulation and bone turnover that would occur with THR-α activation 1
This represents the first approved pharmacologic approach specifically targeting the metabolic pathways underlying MASH, rather than treating secondary complications 1