Madrigal Reveals Two-Year Data Showing Rezdiffra™ Benefits in Compensated MASH Cirrhosis

Madrigal Pharmaceuticals, Inc., a company dedicated to developing novel treatments for metabolic dysfunction-associated steatohepatitis (MASH), has announced encouraging results from a two-year study involving Rezdiffra (resmetirom) for patients with compensated MASH cirrhosis. The findings, drawn from the Phase 3 MAESTRO-NAFLD-1 trial, reveal significant reductions in liver stiffness, a commonly used surrogate measure for liver fibrosis, achieved through vibration-controlled transient elastography (VCTE).

The MAESTRO-NAFLD-1 trial involved an open-label arm with patients suffering from compensated MASH cirrhosis. After two years of treatment, data from 101 patients were analyzed. Initial liver stiffness was noted at 25 kPa, with the treatment group experiencing an average reduction of 6.7 kPa over the study period, which was statistically significant compared to baseline levels. This decrease marks the most substantial reduction in liver stiffness reported for an F4c MASH population to date.

Dr. Mazen Noureddin, a Professor of Medicine and an authority in liver research, commented on these results, emphasizing their potential to lower patients’ risk category for liver-related events. The reduction seen aligns with the "Baveno rule of 5 kPa" used to assess liver risk. The data underscore the predictive power of VCTE for clinical outcomes, potentially surpassing traditional liver biopsy assessments for determining fibrosis stages.

Analyzing the data further, 51% of the patients achieved a reduction in liver stiffness of 25% or more, a milestone associated with decreased progression to end-stage liver disease. The safety profile of Rezdiffra during the trial was consistent with previous studies, showing a low incidence of therapy discontinuation due to adverse events.

Dr. Becky Taub, Madrigal's Chief Medical Officer, highlighted the critical need for effective treatments for MASH cirrhosis due to the considerably heightened risk of liver-related mortality. With the absence of approved therapeutic options, the results from the MAESTRO-NAFLD-1 trial solidify the company's commitment to the ongoing MAESTRO-NASH OUTCOMES trial. Success in this trial could position Rezdiffra as the inaugural therapy for F2-F4c MASH. However, Rezdiffra's usage for compensated MASH cirrhosis will remain restricted until its safety and efficacy are validated in ongoing studies and receive regulatory approval.

The FDA's guidance suggests that clinical trials for MASH cirrhosis should focus on clinical outcomes rather than biopsy-based surrogate endpoints. This guidance, alongside data from the MAESTRO-NAFLD-1 trial, has shaped the design of the ongoing MAESTRO-NASH OUTCOMES trial.

Currently, Rezdiffra is approved for treating adults with noncirrhotic MASH exhibiting moderate to advanced liver fibrosis, contingent upon confirmation of its clinical benefits in ongoing studies. However, it is not approved for patients with MASH cirrhosis.

MASH, previously known as NASH, is a severe liver condition that can escalate to cirrhosis and life-threatening complications, including liver cancer and the necessity for liver transplantation. With an estimated 1.5 million diagnosed cases in the U.S., MASH is increasingly recognized as a significant health concern. Madrigal's focus is on reaching patients with progressive liver fibrosis who are under specialized care, aiming to address an anticipated rise in MASH prevalence.

Rezdiffra is specifically indicated for noncirrhotic MASH with significant fibrosis and is undergoing further trials to confirm its broader clinical benefits. It's essential for patients and healthcare providers to adhere strictly to the prescription and be aware of potential side effects and interactions with other medications.