Madrigal Pharmaceuticals announced positive two-year results from the compensated metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis arm of the phase 3 MAESTRO-NAFLD-1 trial of Rezdiffra.
Rezdiffra is a once-daily, oral, liver-directed THR-β agonist designed to target key underlying causes of MASH. It was approved in March 2024 for the treatment of stage F2 and F3 noncirrhotic MASH with moderate to advanced liver fibrosis. It is the first approved medication for the treatment of MASH in the U.S.
Madrigal, looking to expand Rezdiffra into patient populations with compensated MASH cirrhosis (F4c), has now announced two-year biomarker results from this patient group.
Patients (n=122) in the study achieved significant improvements from baseline in liver stiffness, liver fat, fibrosis biomarkers, liver volume and risk scores for clinically significant portal hypertension (CSPH). CSPH is a major consequence of cirrhosis and is responsible for its most severe complications, including ascites, variceal bleeding and hepatic encephalopathy.
According to Madrigal, among patients with CSPH at baseline, 65% moved into lower risk categories by year two. Among patients with probable CSPH at baseline, 57% moved into the no/low CSPH category as compared to 14% who moved into the CSPH category by year two.
“A larger placebo-controlled study will be needed to confirm Rezdiffra’s benefit in F4c, but the totality of data in this high-risk population of patients on the cusp of progressing to liver decompensation is highly encouraging as we await results from the ongoing phase 3 MAESTRO-NASH OUTCOMES trial of Rezdiffra,” said Naim Alkhouri, M.D., Chief Academic Officer at Summit Clinical Research and the Director of the Steatotic Liver Disease Program at the Clinical Research Institute of Ohio.