CONSHOHOCKEN, PA — Madrigal Pharmaceuticals (Nasdaq: MDGL) reported new clinical and real-world data suggesting its liver disease drug Rezdiffra may reduce both cardiovascular and liver-related risk markers in patients with metabolic dysfunction-associated steatohepatitis (MASH), as the company works to expand evidence supporting the first approved treatment in a growing market.
The findings, presented at the European Association for the Study of the Liver Congress in Barcelona, included analyses from the Phase 3 MAESTRO clinical program and multiple real-world studies evaluating patients treated with Rezdiffra in routine practice.
The data are significant because cardiovascular disease remains the leading cause of death among patients with MASH, while progression to cirrhosis can result in liver failure, cancer, transplantation, and premature mortality.
A secondary analysis of the Phase 3 MAESTRO-NASH and MAESTRO-NAFLD-1 trials found Rezdiffra reduced several cardiovascular risk markers, including low-density lipoprotein cholesterol (LDL-C), apolipoprotein B, and lipoprotein(a), regardless of whether patients were also taking statins.
Among statin-treated patients receiving Rezdiffra, 44.4% of those with elevated LDL-C levels reduced them below 70 mg/dL after 52 weeks. In patients with elevated lipoprotein(a), more than one-third fell below key cardiovascular-risk thresholds.
Dr. Meena Bansal of the Icahn School of Medicine at Mount Sinai said the findings are notable because cardiovascular disease is the leading cause of death in patients with MASH and because statins typically have limited effects on lipoprotein(a).
Madrigal also reported data involving patients with compensated MASH cirrhosis, a population for which no therapies are currently approved.
Using the ANTICIPATE-NASH risk model, researchers analyzed patients from the open-label extension of the MAESTRO-NAFLD-1 trial who received Rezdiffra for up to two years. The proportion of patients classified as high risk for clinically significant portal hypertension fell from 75% at baseline to 54.5% after two years of treatment.
Average ANTICIPATE-NASH scores declined by as much as 37.6% over the same period, while liver-related events occurred only among patients who entered the study with elevated baseline risk scores.
The company also presented several real-world analyses examining patients treated with Rezdiffra for periods ranging from approximately nine to 12 months.
In one study, 48.6% of patients achieved at least a 25% reduction in liver stiffness, a commonly used measure of treatment response. Another analysis of 728 patients found significant reductions in liver enzymes and cholesterol levels over 12 months.
Treatment discontinuations related to adverse events were reported in less than 1% of patients in one real-world cohort.
Rezdiffra, known generically as resmetirom, is a once-daily oral therapy approved in the United States and Europe for adults with noncirrhotic MASH and moderate-to-advanced fibrosis. The drug received approval based on improvements in liver inflammation and fibrosis, with ongoing studies intended to confirm long-term clinical benefit.
MASH, previously known as nonalcoholic steatohepatitis, has emerged as one of the fastest-growing causes of liver transplantation. Patients with moderate-to-advanced fibrosis face sharply elevated risks of liver-related complications, while those who progress to cirrhosis face substantially higher mortality rates.
The new data are part of Madrigal’s effort to build evidence that Rezdiffra may provide benefits beyond slowing liver disease progression, potentially addressing cardiovascular risk factors that contribute significantly to mortality in the MASH population.
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