Madrigal Pharmaceuticals has announced the completion of patient enrollment for the MAESTRO-NASH OUTCOMES trial, a Phase 3 study evaluating resmetirom as a potential treatment for compensated nonalcoholic steatohepatitis (NASH) cirrhosis. This milestone brings the company closer to potentially providing the first approved medication for this high-risk patient group.
The MAESTRO-NASH OUTCOMES trial is a Phase 3, double-blind, randomized, placebo-controlled trial involving 845 patients with compensated NASH cirrhosis. Patients were randomized to receive either 80 mg of resmetirom or a matching placebo once daily. The study duration is expected to last two to three years to accrue the required number of clinical outcome events, primarily focusing on the progression to liver decompensation events.
Urgent Need for NASH Therapies
NASH is a leading cause of liver transplantation in the U.S., particularly among women, and represents an increasing burden on healthcare systems worldwide. The disease is associated with high rates of liver-related mortality, especially as patients progress to more advanced stages of liver fibrosis and cirrhosis. Madrigal's Chief Executive Officer, Bill Sibold, emphasized the urgent need for effective therapies to prevent progression to more severe complications, including the need for liver transplants.
The company's confidence in the trial is supported by positive 52-week data from a previous Phase 3 study, MAESTRO-NAFLD-1, which examined 180 patients with compensated NASH cirrhosis. Chief Medical Officer Becky Taub highlighted resmetirom's antifibrotic profile as a liver-directed THR-β agonist, which has shown promise in earlier trials. Primary results from the MAESTRO-NAFLD-1 trial were published in Nature Medicine in October 2023.
Resmetirom's Potential Impact
Resmetirom has already received accelerated approval for the treatment of NASH with moderate to advanced liver fibrosis based on earlier data. A positive outcome from the MAESTRO-NASH OUTCOMES trial is expected to support full approval of Rezdiffra for noncirrhotic NASH and could expand its indication to patients with compensated NASH cirrhosis.
Madrigal is also conducting other Phase 3 clinical trials, including the MAESTRO-NAFLD-1 (Safety) study, to evaluate the safety and tolerability of resmetirom. The MAESTRO-NASH OUTCOMES trial is one of several Phase III clinical studies that Madrigal is carrying out to evaluate resmetirom. Other trials of the drug include MAESTRO-NASH, which focuses on moderate to advanced fibrosis, and the MAESTRO-NAFLD-1 study.
MASH Drug Development Paradigm
The development of therapies for metabolic dysfunction-associated steatohepatitis (MASH) has entered an exciting new phase with several critical Phase III trials now underway. These trials are poised to revolutionise the approach to MASH, a disease strongly linked to obesity, type 2 diabetes (T2D), and other metabolic disorders. As new drugs move through these advanced clinical stages, the potential to reshape MASH treatment is more tangible than ever.
Madrigal's Commitment to NASH Research
Madrigal Pharmaceuticals is dedicated to long-term leadership in NASH research and development, aiming to shape the treatment paradigm for the disease over the coming decade. Madrigal has also announced the appointment of Dr. Michael R. Charlton, a renowned expert in NASH, as Senior Vice President of Clinical Development, strengthening its commitment to NASH research and innovation. The company is preparing for a potential European launch of REZDIFFRA in mid-2025, backed by a cash reserve of over $1 billion as of the second quarter of 2024. These are the recent developments in the company's ongoing efforts to improve treatment options for NASH patients.
