CONSHOHOCKEN, PA — Madrigal Pharmaceuticals, Inc. (NASDAQ: MDGL) unveiled new two-year data showing that its flagship therapy Rezdiffra produced sustained improvements in patients with compensated MASH cirrhosis, a population with no approved treatment options and extremely high mortality risk. The results, from the Phase 3 MAESTRO-NAFLD-1 trial, were presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting® in Washington, D.C.
The open-label study found that Rezdiffra significantly reduced liver stiffness, improved fibrosis biomarkers, and lowered markers tied to clinically significant portal hypertension — a major driver of liver-related complications. Improvements in disease-specific quality-of-life measures were also sustained through two years of therapy.
Madrigal emphasized that the findings offer rare insight into a difficult-to-treat subset of cirrhotic patients, including those with platelet counts below 100,000/µL, a group typically excluded from advanced-stage MASH trials. In this more vulnerable cohort, Rezdiffra produced consistent improvements across imaging, liver enzymes, lipids, and Baveno risk scores.
Naim Alkhouri, M.D., who presented the results, said the trial expands understanding of how Rezdiffra performs in patients nearing liver decompensation. He noted that Rezdiffra drove measurable benefits even in those with advanced compensated disease, despite a documented interruption in therapy. “These data give me greater confidence in the ongoing Phase 3 MAESTRO-NASH OUTCOMES trial,” he said.
Treatment Pause Underscores a Serious Concern
A separate analysis from the MAESTRO-NAFLD open-label extension found that patients who paused treatment — on average for 77 to 111 days — saw a reversal of earlier gains and evidence of renewed disease progression. Benefits returned once therapy resumed, but Madrigal said the pattern highlights the need for continuous treatment.
Chief Medical Officer David Soergel said the data provide clarity for clinicians and patients weighing long-term management. “We now have compelling evidence that continuous treatment maintained benefit and prevented progression,” he said. “Stopping therapy resulted in an immediate return of disease activity.”
Quality-of-Life Benefits Reinforced Across Trials
In a pooled analysis of more than 1,300 patients, Rezdiffra significantly improved multiple measures of liver disease quality of life in both cirrhotic and noncirrhotic populations. Gains were seen in fatigue, emotional function, abdominal symptoms, and overall health distress — with improvements maintained through Year 2.
Broad Clinical Program Continues to Advance
Madrigal’s robust presence at AASLD included data across metabolic-associated steatotic liver disease (MASLD) populations and disease stages. The company highlighted:
- Meaningful improvements in liver stiffness at two years for both cirrhotic and noncirrhotic cohorts
- Shift of two-thirds of patients to lower Baveno CSPH risk categories
- Improvements in ALT, GGT, CK-18, PRO-C3, adiponectin, and atherogenic lipid markers
- Strong safety profile consistent across studies, with low discontinuation rates
Rezdiffra, a thyroid hormone receptor-β agonist, is the first approved medication for noncirrhotic MASH with moderate to advanced fibrosis (F2–F3) in the U.S. and Europe. It is not approved for patients with cirrhosis, and safety and efficacy in that population remain under investigation.
A Disease With Rising Prevalence — and High Stakes
MASH is a progressive liver disease that can lead to cirrhosis, liver failure, and premature death. Patients who progress to cirrhosis face a 42-fold higher risk of liver-related mortality. As diagnosis increases and disease prevalence rises, the number of patients with advanced fibrosis or compensated cirrhosis is expected to grow sharply, underscoring an urgent need for effective therapies.
Madrigal’s ongoing Phase 3 MAESTRO-NASH OUTCOMES trial will be key in determining whether Rezdiffra can secure expanded approval for compensated cirrhosis. The company said its emerging body of data strengthens the case for use across a wider spectrum of F2–F4c disease.
With encouraging long-term signals, consistent safety, and clear evidence that treatment must be continuous to sustain benefits, Madrigal is positioning Rezdiffra as the potential backbone therapy for MASH — and as one of the most closely watched liver drugs in development today.
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