FDA Sets PDUFA Date for Drug to Treat Patients with NASH

The FDA has accepted the new drug application (NDA) seeking accelerated approval for Madrigal Pharmaceuticals’ resmetirom to treat adult patients with nonalcoholic steatohepatitis (NASH) who have liver fibrosis. The agency has granted priority review and assigned a Prescription Drug User Fee Act date for resmetirom of March 14, 2024.

Nonalcoholic steatohepatitis is a more advanced form of nonalcoholic fatty liver disease (NAFLD), which is estimated to affect about 30% adults in the United States. NASH is a leading cause of liver-related mortality, especially for those with more advanced metabolic risk factors such as hypertension and type 2 diabetes.

In NASH, thyroid hormone beta activity in the liver is impaired, leading to a reduction in mitochondrial function and beta-oxidation of fatty acids, which in turn drive inflammation and liver fibrosis. Resmetirom is a once daily, oral, thyroid hormone receptor (THR)-β selective agonist.

Bill Sibold

“NASH with liver fibrosis represents a significant unmet need in healthcare today: the disease has a serious impact on patients and, without treatment, it can lead to increased risk of cirrhosis, liver failure, liver cancer, and premature mortality,” Bill Sibold, CEO of Madrigal, said in a press release. “Resmetirom is a liver-directed therapy that has demonstrated the potential to treat the liver fibrosis that is associated with these negative outcomes, while resolving the underlying steatohepatitis that drives the disease.”

The application is based on the pivotal phase 3 MAESTRO-NASH, where resmetirom achieved both liver histological improvement endpoints: resolution of NASH and reduction of liver fibrosis. These endpoints had been proposed by FDA to support accelerated approval for the treatment of NASH with liver fibrosis. In both MAESTRO-NASH and the phase 3 safety study MAESTRO-NAFLD-1, LDL cholesterol and triglyceride were reduced by resmetirom and patients achieved potentially meaningful improvements in noninvasive measures of liver health.

About 1,750 patients were enrolled in the MAESTRO-NASH study, which is continuing to assess patients after the initial 52-week treatment period for up to 54 months. This portion of the study is designed to generate confirmatory data that and will measure hepatic clinical outcome events including progression to cirrhosis on biopsy and hepatic decompensation events, as well as all-cause mortality.

A separate 52 week phase 3 clinical trial, an open-label active treatment extension study of MAESTRO-NAFLD-1 (MAESTRO-NAFLD-OLE) in about 700 patients is also ongoing.

This story originally appeared on Managed Healthcare Executive.