Madrigal Pharmaceuticals has announced positive two-year data from the open-label compensated MASH cirrhosis (F4c) arm of the Phase 3 MAESTRO-NAFLD-1 trial, demonstrating the potential benefit of Rezdiffra (resmetirom) in patients with this advanced liver disease. The data, presented on February 26, 2025, highlight significant reductions in liver stiffness, a key indicator of fibrosis, as measured by vibration-controlled transient elastography (VCTE). These findings offer hope for a patient population with limited treatment options.
Significant Reduction in Liver Stiffness
The MAESTRO-NAFLD-1 trial included an open-label active treatment arm of patients with compensated MASH cirrhosis. The new analysis included 101 patients with VCTE results after two years of treatment. The results showed:
- A mean 6.7 kPa reduction in liver stiffness from a baseline of 25 kPa, which was statistically significant (p<0.05).
- 51% of patients achieved a ≥25% reduction in liver stiffness.
Mazen Noureddin, M.D., M.H.Sc., Professor of Medicine, Director Houston Research Institute and C.S.O. Summit Clinical Research, noted that a mean 6.7 kPa reduction suggests that many patients are moving into a lower risk category. He also highlighted recently published, multi-center, longitudinal studies demonstrating VCTE is a strong predictor of clinical outcomes and may be more predictive of clinical outcomes than fibrosis stage assessed by liver biopsy.
Safety and Tolerability
The safety and tolerability profile of Rezdiffra in the compensated MASH cohort of MAESTRO-NAFLD-1 was consistent with other Rezdiffra clinical trials, with a low rate of discontinuations due to adverse events.
Implications for Future Treatment
Becky Taub, M.D., Chief Medical Officer and President of Research & Development of Madrigal, emphasized the urgent need for improved care for patients with MASH cirrhosis, who face a 42 times higher risk of liver-related mortality. The new two-year data from MAESTRO-NAFLD-1 reinforce confidence in the ongoing, fully enrolled MAESTRO-NASH OUTCOMES trial of Rezdiffra in patients with compensated MASH cirrhosis. If the OUTCOMES trial is successful, Rezdiffra has the potential to become the first therapy for F2-F4c MASH.
Financial Highlights and Future Growth
Madrigal Pharmaceuticals reported fourth-quarter and full-year 2024 Rezdiffra net sales of $103.3 million and $180.1 million, respectively. As of year-end 2024, more than 11,800 patients were on Rezdiffra. The company's cash, cash equivalents, restricted cash, and marketable securities totaled $931.3 million as of December 31, 2024.
The company is also preparing for European expansion, with a marketing authorization application under review by the European Medicines Agency. Pending approval, Madrigal expects a phased European launch of Rezdiffra beginning in the second half of 2025.
About Rezdiffra
Rezdiffra is a prescribed medicine used along with diet and exercise to treat adults with nonalcoholic steatohepatitis (NASH) with moderate to advanced liver scarring (fibrosis), but not with cirrhosis of the liver. It is a THR-β agonist designed to target key underlying causes of MASH.
