Resmetirom Shows Promising NASH Trial Results Pre-PDUFA

A recent Phase III clinical trial has indicated that Madrigal Pharmaceuticals' oral drug, resmetirom, could be a groundbreaking treatment for nonalcoholic steatohepatitis (NASH). The study, detailed in The New England Journal of Medicine, showed that resmetirom was notably more effective than a placebo in achieving the resolution of NASH and improving liver fibrosis.

Resmetirom is poised to become the first-ever medicine specifically approved for NASH, with a Prescription Drug User Fee Act (PDUFA) date scheduled for March 14. Madrigal Pharmaceuticals initially reported positive outcomes from the MAESTRO-NASH trial in 2022, where resmetirom was compared to a placebo in treating NASH patients with substantial fibrosis.

The MAESTRO-NASH trial's results, published in the NEJM, offered a comprehensive look at the drug's efficacy and safety. Madrigal highlighted that the trial was the first to meet the FDA's proposed primary endpoints for predicting clinical benefits in NASH: resolution of NASH without fibrosis worsening and fibrosis reduction without an increase in NAFLD activity score.

In the 80mg and 100mg dosage groups, 25.9% and 29.9% of patients, respectively, achieved NASH resolution without fibrosis worsening, compared to only 9.7% in the placebo group, which was a statistically significant difference. Additionally, 24.2% and 25% of patients in the 80mg and 100mg groups, respectively, showed at least one stage improvement in fibrosis without affecting the NAFLD activity score, versus 14.2% in the placebo group.

Madrigal also reported that resmetirom achieved multiple secondary endpoints, such as a significant reduction in liver enzymes, fibrosis biomarkers, and improvements in imaging tests, as well as a decrease in atherogenic lipids and lipoproteins.

Becky Taub, Madrigal's Chief Medical Officer, expressed confidence that resmetirom could revolutionize the treatment of NASH with significant fibrosis if granted accelerated approval by the FDA. The company also emphasized the drug's safety profile, noting that transient diarrhea and nausea were reported early in therapy but subsided after the initial weeks, with no cases of drug-induced liver injury.

Madrigal's CEO, Bill Sibold, stated that the MAESTRO-NASH trial's results present a unique opportunity to establish resmetirom as the foundational therapy for NASH with significant fibrosis, potentially transforming care for patients who currently lack approved treatment options.