Madrigal Pharmaceuticals, Inc. received accelerated approval from the U.S. FDA for Rezdiffra (resmetirom) in conjunction with diet and exercise for the treatment of adults with noncirrhotic NASH with moderate to advanced liver fibrosis. Continued approval for this indication may be contingent upon verification and description of clinical benefit in ongoing confirmatory trials.
 
Rezdiffra is a once-daily, oral THR-β agonist designed to target key underlying causes of NASH. The accelerated approval of Rezdiffra was based on results from the Phase 3 MAESTRO-NASH trial. MAESTRO-NASH is an ongoing randomized, double-blind, placebo-controlled trial that enrolled 1,759 patients with biopsy-confirmed NASH. Following 52 weeks of treatment, both 100 mg and 80 mg doses of Rezdiffra demonstrated statistically significant improvement compared to placebo on two primary endpoints: NASH resolution with no worsening of fibrosis, and an improvement in fibrosis by at least one stage with no worsening of the NAFLD activity score. Fibrosis improvement and NASH resolution were consistent regardless of age, gender, type 2 diabetes status, or fibrosis stage.
 
The Rezdiffra prescribing information does not include a liver biopsy requirement for diagnosis. The recommended dosage of Rezdiffra is based on actual body weight. For patients weighing <100 kg (220 lbs.), the recommended dosage is 80 mg orally once daily. For patients weighing ≥100 kg (220 lbs.), the recommended dosage is 100 mg orally once daily.

Nonalcoholic steatohepatitis (NASH) is a more advanced form of nonalcoholic fatty liver disease (NAFLD). NASH is a leading cause of liver-related mortality. Patients with NASH, especially those with more advanced metabolic risk factors (hypertension, concomitant type 2 diabetes), are at increased risk for adverse cardiovascular events and increased morbidity and mortality.