EMA committee recommends approval of Madrigal Pharma’s resmetirom to treat MASH with moderate to advanced liver fibrosis
Madrigal Pharmaceuticals, Inc., a biopharmaceutical company focused on delivering novel therapeutics for metabolic dysfunction-associated steatohepatitis (MASH), announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending approval of resmetirom (Rezdiffra) for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis. The European Commission decision is anticipated in August.
Bill Sibold, chief executive officer of Madrigal, stated, “Madrigal is singularly focused on leading the fight against MASH globally. Resmetirom was the first medication to achieve fibrosis improvement and MASH resolution in a phase 3 trial, the first medication to receive FDA-approval for MASH, and today’s positive CHMP opinion represents another historic first for the global MASH community. MASH is the fastest-growing indication for liver transplantation in Europe, and we believe resmetirom has the potential to address the urgent unmet need for a foundational, liver-directed therapy to treat patients with this serious disease.”
• MASH (Metabolic dysfunction-associated steatohepatitis) is a leading cause of liver-related deaths and a growing global healthcare burden.
• Resmetirom is an oral, once-daily, liver-directed THR-ß (thyroid hormone receptor beta) agonist.
• It is specifically designed to target the underlying mechanisms driving MASH.
• The Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion on resmetirom.
• This was based on its favorable benefit-risk profile and encouraging clinical data.
• The pivotal Phase 3 MAESTRO-NASH trial demonstrated success in achieving both primary endpoints:
- Significant reduction in liver fibrosis
- Resolution of MASH
Jörn M. Schattenberg, M.D., Professor of Medicine and Director of the Department of Medicine at the University Medical Center Homburg and University of the Saarland in Germany, stated, “I’m encouraged by the CHMP’s positive opinion recommending approval of resmetirom. After years of clinical research and growing appreciation of the burden of MASH on patients and health systems across Europe, we are finally on the cusp of having an approved therapy that targets the underlying disease. Importantly, resmetirom is already included in European clinical practice guidelines, which provide a framework for identifying and monitoring patients with noninvasive tests. If approved, I believe the medication has the potential to transform care for my patients with MASH.”
• The US Food and Drug Administration (FDA) granted accelerated approval in March 2024 for Rezdiffra in conjunction with diet and exercise for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).
• Continued approval for this indication may be contingent upon verification and description of clinical benefit in ongoing confirmatory trials.
• Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), is a serious liver disease that can progress to cirrhosis, liver failure, liver cancer, need for liver transplantation, and premature mortality.
• MASH is the leading cause of liver transplantation in women and the second leading cause of all liver transplantation in the US, and the fastest-growing indication for liver transplantation in Europe.
• Progression to MASH with moderate to advanced fibrosis (stages F2–F3) significantly increases the risk of adverse liver outcomes.
• Patients at this stage have a 10–17 times higher risk of liver-related mortality compared to those without fibrosis.
• Once MASH progresses to cirrhosis, the risk of liver-related mortality rises even more—up to 42 times higher.
• These statistics highlight the critical importance of treating MASH early, before cirrhosis and its complications develop.
• Beyond liver outcomes, MASH is also an independent risk factor for cardiovascular disease, which is the leading cause of death among these patients.
As MASH disease awareness improves and disease prevalence increases, the number of diagnosed patients with MASH with moderate to advanced fibrosis or compensated MASH cirrhosis (F2-F4c) is expected to grow.
• Rezdiffra is a once-daily, oral, liver-directed THR-ß agonist designed to target key underlying causes of MASH.
• It is the first approved medication for the treatment of MASH in the US.
• In the pivotal phase 3 MAESTRO-NASH biopsy trial, Rezdiffra achieved both fibrosis improvement and MASH resolution primary endpoints, and 91% of patients treated with Rezdiffra 100 mg experienced improvement or stabilization of liver stiffness.
• In the US, Rezdiffra is indicated in conjunction with diet and exercise for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).
• Continued approval for this indication may be contingent upon verification and description of clinical benefit in ongoing confirmatory trials.
• Rezdiffra is not approved in Europe for the treatment of patients with MASH with moderate to advanced liver fibrosis and not approved in any geography for the treatment of patients with cirrhosis.
• The ongoing, fully enrolled MAESTRO-NASH OUTCOMES trial is evaluating progression to liver decompensation events in patients with compensated MASH cirrhosis treated with Rezdiffra versus placebo.
• Madrigal Pharmaceuticals, Inc. is a biopharmaceutical company focused on delivering novel therapeutics for metabolic dysfunction-associated steatohepatitis (MASH), a liver disease with high unmet medical need.
• Madrigal’s medication, Rezdiffra (resmetirom), is a once-daily, oral, liver-directed THR-ß agonist designed to target key underlying causes of MASH.