Madrigal builds in MASH with $4.4bn+ Ribo alliance

Madrigal Pharma was the first drugmaker to bring a treatment for metabolic dysfunction-associated steatohepatitis (MASH) to market, and has now signed a major alliance with China's Ribo Life Science to keep its pipeline for the liver disorder topped up.

The licensing deal, which spans six preclinical-stage MASH candidates, includes an upfront payment to Ribo of $60 million, with another $4.4 billion in cumulative payments. The six candidates are siRNA-based gene silencing candidates against a range of as-yet undisclosed genetic targets.

It comes just a few weeks after Madrigal licensed another MASH candidate from Pfizer for $50 million upfront, and extends the company's shots on goal in MASH as it moves towards combination therapies.

The Philadelphia biotech 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 fibrosis (F2/F3), but who have not developed cirrhosis.

Sales of Rezdiffra have already gathered considerable momentum, looking set to approach $1 billion in 2025, its first full year on the market. It goes into 2026, however, facing its first competition, after Novo Nordisk's GLP-1 agonist Wegovy (semaglutide) had its label extended to include MASH.

"We believe meeting future patient needs in MASH will require combination approaches and treatments tailored to genetic drivers of disease," said Bill Sibold, Madrigal's chief executive, who added that the company "is uniquely positioned to shape the future treatment landscape in this rapidly expanding market."

The Pfizer deal provided Madrigal with a phase 2 oral DGAT-2 inhibitor, which is due to start a phase 2 combination study with Rezdiffra later this year, and the company's pipeline is also working on MGL-2086, an oral GLP-1 agonist licensed from CSPC Pharma, with human testing scheduled to begin in the second quarter.

Meanwhile, a phase 3 trial of Rezdiffra that aims to extend its label to include patients with compensated MASH cirrhosis, an indication that Madrigal has previously said could double the market opportunity for the drug. The results of that outcomes study should be forthcoming next year.

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.