Madrigal Pharmaceuticals’ Rezdiffra (resmetirom) has been approved in Europe for the treatment of metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis, making it the first targeted therapy available for patients in the region with this severe form of liver disease.
The conditional marketing authorisation by the European Commission (EC) follows an approval recommendation by the European Medicines Agency (EMA)’s Medicinal Products for Human Use (CHMP) in June.
US pharma Madrigal expects to launch Rezdiffra in Europe on a country-by-country basis, starting with Germany in Q4 2025, as per a 19 August statement.
Stock in US-listed Madrigal closed 2.2% down to $379.55 per share at market close on 19 August, with investors likely downbeat amid a tangential development. Viking’s oral glucagon-like peptide-1 receptor agonist (GLP-1RA) drug posted disappointing trial results on the same day; Madrigal recently outlaid $2bn in an oral GLP-1RA licensing deal.
The regulatory approval means Madrigal is the only pharmaceutical company with an approved MASH drug in Europe. Rezdiffra was also the first MASH treatment to market in the US – winning US Food and Drug Administration (FDA) approval in March 2024.
MASH develops when there is a significant buildup of fat in the liver. Fibrosis, also known as scarring, is associated with MASH, and left untreated, it can lead to more serious damage, including cirrhosis.
Madrigal estimates that approximately 370,000 patients have been diagnosed with MASH with moderate to advanced fibrosis in Europe. The disease is a form of non-alcoholic fatty liver disease (NAFLD) that has been billed as one of pharma’s highest potential growth areas.
Analysis by GlobalData forecasts sales of $25.7bn in 2032 across the seven major markets (the US, France, Germany, Italy, Spain, the UK, and Japan), meaning Madrigal's first-to-market credentials in both the US and Europe could bode well for the drug’s growth.
GlobalData forecasts a high ceiling for Rezdiffra. The drug is expected to reach blockbuster status by the end of 2026, and, by 2031, Rezdiffra is forecast to generate $4.8bn in global sales.
GlobalData is the parent company of Pharmaceutical Technology.
Administered as a daily pill, Rezdiffra works by activating a thyroid hormone receptor that reduces liver fat accumulation.
While Madrigal was first to reach market in the US for a MASH treatment, it has since lost its crown of boasting the only approved therapy in the indication. Earlier this week, Novo Nordisk’s blockbuster drug Wegovy (semaglutide) won FDA approval for the treatment of MASH with moderate to advanced liver fibrosis, providing direct competition to Rezdiffra. Novo Nordisk has also applied for regulatory approval in the EU, setting up a second potential rivalry with Madrigal.
However, unlike Wegovy, which exerts its effect through agonism of the GLP-1 receptors, Madrigal’s treatment works directly in the liver itself.
GlobalData senior analyst Jay Patel says: "This approval allows Madrigal's Rezdiffra to establish an early lead in the EU MASH market. Nevertheless, Novo Nordisk's Wegovy is set to follow closely behind, with an approval expected imminently.
"It remains to be seen whether Rezdiffra will be able to carve out a niche once this takes place, given greater patient and physician familiarity with Wegovy, which is already approved for common MASH comorbidities such as obesity and type 2 diabetes mellitus."
The EC based its approval on results from the Phase III MAESTRO-NASH trial, in which Rezdiffra achieved both fibrosis reduction and MASH resolution primary endpoints. The pill also reduced liver stiffness, liver fat, liver enzymes, and atherogenic lipids in the MAESTRO-NASH trial, and improved health-related quality of life.
Madrigal’s CEO Bill Sibold said: “MASH is the fastest-growing indication for liver transplantation in Europe, but until now, it had no approved treatment. The European labelling for Rezdiffra will set an important precedent for the entire field, with no biopsy required to qualify for treatment with Rezdiffra and a clear focus on a distinct MASH patient population with high unmet need.”
Before Madrigal and Novo’s approvals, MASH had become a graveyard of failed candidates. Gilead, AstraZeneca, and Intercept all fell short in getting candidates to market, all eventually pivoting pipelines away from the indication.
