Madrigal Pharmaceuticals, Inc. announced that Rezdiffra (resmetirom) is now available in the U.S. Rezdiffra is indicated in conjunction with diet and exercise for the treatment of adults with noncirrhotic NASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis). Continued approval for this indication may be contingent upon verification and description of clinical benefit in ongoing confirmatory trials. The introduction of Rezdiffra as the first and only FDA-approved therapy in NASH marks a turning point for Madrigal and the NASH community.

Rezdiffra is a once-daily, oral THR-ß 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, which was published in the New England Journal of Medicinein February 2024. MAESTRO-NASH remains ongoing as an outcomes study designed to generate confirmatory data that, if positive, will help verify clinical benefit and may support full approval.

A second ongoing outcomes trial is evaluating progression to liver decompensation events in patients with well-compensated NASH cirrhosis treated with Rezdiffra versus placebo. The recommended dosage of Rezdiffra is based on actual body weight. For patients weighing About NASH Nonalcoholic steatohepatitis (NASH) is a more advanced form of nonalcoholic fatty liver disease (NAFLD).

NASH is a leading cause of liver-related mortality and an increasing burden on healthcare systems globally. Additionally, 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. Once patients progress to NASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis), the risk of adverse liver outcomes increases dramatically.

NASH is rapidly becoming the leading cause of liver transplantation in the U.S. Madrigal estimates that approximately 1.5 million patients have been diagnosed with NASH in the U.S., of which approximately 525,000 have NASH with moderate to advanced liver fibrosis. Madrigal plans to focus on approximately 315,000 diagnosed patients with NASH with moderate to advanced liver fibrosis under the care of the liver specialist physicians during the launch of Rezdiffra. NASH is also known as metabolic dysfunction associated steatohepatitis (MASH).

In 2023, global liver disease medical societies and patient groups came together to rename the disease, with the goal of establishing an affirmative, non-stigmatizing name and diagnosis. Nonalcoholic fatty liver disease (NAFLD) was renamed metabolic dysfunction-associated steatotic liver disease (MASLD), NASH was renamed MASH, and an overarching term, steatotic liver disease (SLD), was established to capture multiple types of liver diseases associated with fat buildup in the liver. In addition to liver disease, patients with MASH have at least one related comorbid condition (e.g., obesity, hypertension, dyslipidemia, or type 2 diabetes).