Madrigal eyes combination MASH therapy with Pfizer deal
Bill Sibold, Madrigal Pharma's chief executive.
Madrigal Pharma is reheating a drug for metabolic dysfunction-associated steatohepatitis (MASH) put on ice by Pfizer, hoping to build on its first-mover advantage in therapies for the widespread liver disease.
MASH is a form of non-alcoholic fatty liver disease (NAFLD) that affects millions of people and which, for several years, has been billed as pharma's next big growth area, with some analysts predicting a market potentially worth tens of billions of dollars a year.
The Philadelphia biopharma was the first to bring a therapy to market for MASH in 2024 after it won US approval for THR beta-selective agonist Rezdiffra (resmetirom) as a treatment for MASH patients with moderate to advanced liver scarring (fibrosis), but who have not developed cirrhosis.
It has now added to its MASH pipeline by licensing rights to Pfizer's oral DGAT-2 inhibitor ervogastat, saying the two mechanisms of action are complementary and could have "potential additive therapeutic benefit."
DGAT-2 inhibitors work by blocking the final step in triglyceride assembly and storage, resulting in lower levels of triglycerides and other lipotoxic fats in the liver, as well as reduced inflammation. Rezdiffra, meanwhile, also reduces fat storage and inflammation in the liver.
Since launch, Rezdiffra has grown quickly to fulfil its blockbuster sales projections, with sales levels – $287 million in the third quarter of 2025 – now putting it well on course for annual turnover above $1 billion and beyond. It has yet to roll out in most major markets, with Germany the first European launch country last September.
Competition has arrived, however, in the form of Novo Nordisk's injectable GLP-1 agonist Wegovy (semaglutide), which had its label expanded to include MASH last year. Madrigal also has an oral GLP-1 agonist in its clinical pipeline for the liver disease.
Pfizer had been developing ervogastat as a combination therapy for MASH with ACC inhibitor clesacostat, but said last November it was stopping the development of the regimen whilst maintaining ervogastat as an active, but low-priority, programme.
Madrigal is paying $50 million upfront for rights to the drug, along with undisclosed milestone payments. More details of the deal may be available later today during Madrigal's presentation at the JPM Healthcare conference in San Francisco.
"Our global license agreement for ervogastat aligns with our long-term leadership ambition, and we believe Madrigal is uniquely positioned to advance this promising phase 2 asset and unlock its full clinical and commercial value through a development programme focused on combination therapy with Rezdiffra," said the company's chief executive, Bill Sibold.
