Madrigal Pharmaceuticals’ Rezdiffra (resmetirom) has demonstrated sustained efficacy in a late-stage trial of patients with liver disease.
The company presented positive two-year results from the open-label compensated metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis arm of its phase 3 MAESTRO-NAFLD-1 trial at this year’s European Association for the Study of the Liver Congress.
An estimated 1.5 million people in the US have been diagnosed with MASH, formerly known as nonalcoholic steatohepatitis, which occurs when too much fat builds up in the liver. The disease can progress to cirrhosis, liver failure, liver cancer and is the leading cause of liver transplantation among women.
Taken orally once daily, Rezdiffra is a liver-directed thyroid-hormone receptor-beta (THR-β) agonist designed to target key underlying causes of MASH. The drug has already been granted accelerated in the US to treat non-cirrhotic cases, but is not currently approved in any market for MASH patients with cirrhosis.
New results from MAESTRO-NAFLD-1 showed that Rezdiffra-treated compensated MASH cirrhosis patients achieved significant improvements from baseline in liver stiffness, liver fat, fibrosis biomarkers, liver volume and risk scores for clinically significant portal hypertension (CSPH), a major consequence of cirrhosis that is linked to severe complications.
Among patients with CSPH at baseline, 65% moved into lower risk categories by year two, while 57% of those with probable CSPH at baseline moved into the no or low CSPH category.
Safety data was also found to be consistent with previous studies, and Rezdiffra was well-tolerated.
Madrigal’s chief medical officer, David Soergel, said: “Lower THR-β activity in the liver is predictive of hepatic decompensation in patients with MASH, so there is a strong mechanistic rationale supporting the potential of Rezdiffra, a THR-β agonist, to improve outcomes in patients with compensated MASH cirrhosis.
“This two-year open-label data from MAESTRO-NAFLD-1 adds important clinical evidence that supports our confidence in the ongoing, fully enrolled phase 3 outcomes trial of Rezdiffra in compensated MASH cirrhosis.”
It is hoped that positive results from the MAESTRO-NASH OUTCOMES study would support the full approval of Rezdiffra for non-cirrhotic MASH and expand the indication to those with cirrhosis.