Madrigal Presents New Phase 3 MAESTRO-NASH Rezdiffra™ Data at EASL Congress

Madrigal Pharmaceuticals, Inc. recently released new findings from their Phase 3 MAESTRO-NASH trial involving Rezdiffra at the EASL Congress in Milan. Rezdiffra, a once-daily oral treatment, has shown significant promise in treating nonalcoholic steatohepatitis (NASH), as evidenced by its accomplishments in the MAESTRO-NASH trial.

Rezdiffra is a thyroid hormone receptor (THR)-β agonist aimed at addressing key underlying causes of NASH. It is the first approved medication for this condition, targeting adults with moderate to advanced liver fibrosis (stages F2 to F3). The drug's approval is contingent upon ongoing confirmatory trials to verify its clinical benefits.

Bill Sibold, CEO of Madrigal, emphasized the importance of the new analyses being presented at the EASL Congress. These analyses incorporate innovative AI technology to provide deeper insights into the antifibrotic effects of Rezdiffra and the role of THR-β in suppressing NASH progression. Sibold highlighted the rapid disease progression in NASH patients, underscoring the significance of Rezdiffra's ability to improve fibrosis and prevent the advancement to decompensated cirrhosis.

Becky Taub, M.D., Chief Medical Officer and President of Research & Development at Madrigal, echoed Sibold's sentiments. She noted the potential of Rezdiffra to reshape the future of NASH treatment, especially for populations historically underrepresented in clinical research, such as those with probable metabolic dysfunction and alcohol-associated liver disease (MetALD).

Key Findings from the MAESTRO-NASH Trial

AI-Based Analysis:
An AI-driven methodology, qFibrosis, identified 30 specific fibrotic features on NASH liver biopsies that may predict progression to cirrhosis. The analysis revealed significant improvements in fibrosis among patients treated with Rezdiffra, compared to placebo. This improvement was particularly pronounced in patients with F3 fibrosis.

Noninvasive Test Data:
Over three years, noninvasive test data demonstrated a durable treatment response to Rezdiffra. Liver stiffness, measured by vibration-controlled transient elastography (VCTE), improved significantly in Rezdiffra-treated patients. 91% of these patients achieved stabilization or improvement in liver stiffness.

Health-Related Quality of Life:
Rezdiffra also showed a positive impact on health-related quality of life (HRQL) in patients with NASH. Improvements were noted in domains such as patient worry, health distress, and stigma, especially in patients who responded to the treatment with fibrosis improvement or NASH resolution.

MetALD Analysis:
In the first analysis of Rezdiffra treatment among patients with MetALD, it was found that these patients achieved rates of fibrosis improvement and steatohepatitis resolution comparable to those in the overall MAESTRO-NASH population. This analysis included 75 patients who were identified based on biomarkers for chronic alcohol consumption.

About the MAESTRO-NASH Trial

The ongoing Phase 3 MAESTRO-NASH trial enrolled 1,759 patients with biopsy-confirmed NASH. Participants were randomized to receive either 80 mg or 100 mg of Rezdiffra, or a placebo. The trial's primary endpoints were the resolution of NASH without worsening fibrosis and improvement in fibrosis without worsening the nonalcoholic fatty liver disease (NAFLD) activity score. Rezdiffra met both primary endpoints and also showed a significant improvement in liver enzymes, fibrosis biomarkers, and imaging tests.

Future Outlook

Patients in the trial continue to receive treatment for up to 54 months, allowing for the accrual and measurement of long-term hepatic clinical outcomes, such as progression to cirrhosis and hepatic decompensation events. These outcomes will help verify Rezdiffra's clinical benefits and may support its full approval.

About NASH and Rezdiffra

NASH is an advanced form of NAFLD and a leading cause of liver-related mortality worldwide. Approximately 1.5 million people in the U.S. are diagnosed with NASH, with 525,000 having moderate to advanced liver fibrosis. Madrigal focuses on treating around 315,000 diagnosed patients with moderate to advanced fibrosis.

Rezdiffra, a prescribed medication, is used in conjunction with diet and exercise to treat adults with NASH and moderate to advanced liver scarring. It is designed to target the liver and improve both NASH and fibrosis. Ongoing studies aim to confirm its clinical benefits further.

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