Originally published by our sister publication Gastroenterology & Endoscopy News

By GEN Staff

The FDA granted accelerated approval to the first medication for the treatment of metabolic dysfunction–associated steatohepatitis, resmetirom (Rezdiffra, Madrigal).

Resmetirom is approved for use in conjunction with diet and exercise for adults with noncirrhotic MASH with moderate to advanced liver fibrosis (stages F2-F3 fibrosis).

“Previously, patients with NASH who also have notable liver scarring did not have a medication that could directly address their liver damage,” said Nikolay Nikolov, MD, the acting director of the Office of Immunology and Inflammation in the FDA’s Center for Drug Evaluation and Research, in an FDA press release. “Today’s approval of [resmetirom] will, for the first time, provide a treatment option for these patients, in addition to diet and exercise.”

The approval of resmetirom, an oral, liver-directed thyroid hormone receptor beta–selective agonist, follows positive findings in its phase 3, randomized controlled trial (MAESTRO-NASH), recently published in The New England Journal of Medicine (2024;390[6]:497-509). In the trial, patients with biopsy-confirmed MASH with fibrosis stages F1B, F2 or F3 (n=966) were randomly assigned to receive either once-daily resmetirom at 80 or 100 mg or placebo.

A greater percentage of patients in the resmetirom groups than in the placebo group did not have fibrosis progression (80 mg, 25.9%; 100 mg, 29.9%; placebo, 9.7%; P<0.001 for both comparisons with placebo). More patients in the intervention arms also saw an improvement in their fibrosis by at least one stage, with no worsening of their nonalcoholic fatty liver disease activity score than in the placebo group (80 mg, 24.2%; 100 mg, 25.9%; placebo, 14.2%; P<0.001 for both comparisons with placebo). Patients in the resmetirom groups also had greater reductions in their levels of low-density lipoprotein cholesterol from baseline to week 24 than in those in the placebo group (80 mg, –13.6%; 100 mg, –16.3%; placebo, 0.1%; P<0.001 for both comparisons with placebo).

The researchers reported that serious adverse events were similar between those taking the drug and those in the placebo group (80 mg, 10.9%; 100 mg, 12.7%; placebo, 11.5%). As for nonserious adverse events, diarrhea and nausea were more common in the resmetirom groups than in the placebo group. Other common adverse events in those taking the drug were pruritus, abdominal pain, vomiting, constipation and dizziness.

The trial is ongoing to continue to collect data that Madrigal hopes will help support a full approval. Along with this trial, another placebo-controlled trial is underway to explore resmetirom’s effects on progression to liver decompensation events in patients with well-compensated MASH cirrhosis, according to the company.

Resmetirom is not indicated for patients with decompensated cirrhosis. The full prescribing information can be found here.

The company said it expects resmetirom to be available through a limited specialty pharmacy network in the United States in April.

Based on FDA and Madrigal press releases.