Madrigal's Rezdiffra promising for compensated MASH cirrhosis

Madrigal Pharmaceuticals has announced encouraging findings regarding its medication, Rezdiffra (resmetirom), which targets liver disease. Presented at the European Association for the Study of the Liver Congress, the results stem from a phase 3 MAESTRO-NAFLD-1 trial focused on patients with compensated metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis.

MASH, previously identified as nonalcoholic steatohepatitis, affects approximately 1.5 million individuals in the United States. This condition arises from excessive fat accumulation in the liver and can evolve into more severe conditions such as cirrhosis, liver failure, and liver cancer. Among women, it is the predominant cause for liver transplants.

Rezdiffra is a groundbreaking medication taken orally once daily. It functions as a liver-directed thyroid-hormone receptor-beta (THR-β) agonist, specifically developed to address the root causes of MASH. While it has received accelerated approval in the United States for non-cirrhotic cases, it remains unapproved globally for MASH patients with cirrhosis.

The recent trial results underscore Rezdiffra's effectiveness, demonstrating significant improvements in patients with compensated MASH cirrhosis. The participants showed advancements in liver stiffness, liver fat, fibrosis biomarkers, and liver volume. Furthermore, there were notable improvements in risk scores for clinically significant portal hypertension (CSPH), a critical issue associated with cirrhosis that can lead to severe complications.

For patients who initially had CSPH, 65% transitioned to lower risk categories after two years. Additionally, 57% of those initially identified with probable CSPH moved to either no CSPH or a low CSPH category by the study's end. The safety profile of Rezdiffra remained consistent with earlier studies, and the drug was well-tolerated among participants.

David Soergel, Madrigal's chief medical officer, emphasized the significance of THR-β activity in the liver. He noted that reduced activity could predict hepatic decompensation in MASH patients, supporting the potential of Rezdiffra, a THR-β agonist, in improving outcomes for those with compensated MASH cirrhosis. Soergel added that the two-year open-label data from MAESTRO-NAFLD-1 bolsters their confidence in the ongoing phase 3 outcomes trial.

The company hopes that favorable outcomes from the MAESTRO-NASH OUTCOMES study will not only facilitate full approval for Rezdiffra to treat non-cirrhotic MASH but also broaden its use to include patients with cirrhosis.