Madrigal Pharmaceuticals’ Rezdiffra blew open the door to the MASH market when it scored the disease’s first FDA approval in 2024. Now Rezdiffra is nearly a blockbuster, raking in almost $1 billion in sales in its first full year on the market and another $311 million in the first quarter of 2026.
Novo Nordisk’s blockbuster GLP-1 Wegovy followed with a MASH approval as well.
Now the red-hot market is set to become more crowded, with large pharmas like GSK and Roche making high-profile acquisitions in the space and several assets in development throughout pharma’s pipeline.
“It’s an untapped sort of market,” said Timothy Blackstock, director with Datamonitor Healthcare at Evaluate, which is part of Norstella. “It’s a chronic disease which is probably going to require long-term treatment, which is always of interest to drug developers.”
MASH is a chronic fatty liver disease that affects an estimated 5.8% of U.S. adults, with rates expected to rise in the coming years. One of its key complications is liver scarring, or fibrosis, and liver failure, with the disease progressing in stages ranging from F1 to the most severe form, F4. It’s also underdiagnosed, is often asymptomatic until later stages and is relatively “new,” having only been defined in the 1980s.
“There’s plenty of room for the market to grow,” Blackstock said. “It’s not just purely by numbers. Rezdiffra has fairly modest efficacy compared to some of the drugs that are coming through.”
Here are three late-stage MASH candidates that could make a large impact on the expanding market.
Inventiva’s potential best-in-class contender
After reprioritizing its pipeline and cutting half of its workforce, Inventiva is now a single-asset company laser-focused on lanifibranor, an oral pan-PPAR (peroxisome proliferator-activated receptors) agonist.
“We think this has best-in-class oral efficacy for the MASH space,” said Andrew Obenshain, CEO of Inventiva, which is setting the candidate up to battle with Rezdiffra.
The two currently FDA-approved products for MASH take different approaches to treating the disease. Rezdiffra directly targets the liver to reduce scarring, while Wegovy addresses the underlying metabolism problems.
“What’s exciting about lanifibranor is that it does both,” Obenshain said.
Data published in the New England Journal of Medicine showed lanifibranor met its primary and secondary endpoints in a phase 2 study, including MASH resolution. Additionally, liver enzyme levels decreased, and lipid, inflammatory and fibrosis biomarkers improved. The company expects a phase 3 readout in the fourth quarter this year, Obenshain said.
Obenshain believes lanifibranor will compete with Rezdiffra for patients in middle stages of the disease.
“We really see F2 and F3 being the market where the patients are going to be on a GLP-1 and then have an oral added on,” he said.
Novo Nordisk’s up-and-comer efruxifermin
Just months after nabbing MASH’s second FDA approval with Wegovy, Novo Nordisk added efruxifermin, an injectable fibroblast growth factor 21 (FGF21) analogue, to its pipeline when it acquired Akero Therapeutics. The candidate, which Novo called a potential first- and best-in-class asset for MASH, is being studied in both F2, F3 and F4 MASH patients.
In its 96-week phase 2b trials, efruxifermin “significantly” improved liver fibrosis and reversed compensated cirrhosis due to MASH. Specifically, the Harmony (F2-F3) and Symmetry (F4) trials demonstrated 49% and 29% reduction in fibrosis without worsening of MASH, respectively.
“The data has been really good,” Blackstock said. “It looks like it’s going to be one of the best on the market if and when it’s approved.”
Its current phase 3 program consists of three clinical trials for pre-cirrhotic (F2-F3) MASH and compensated cirrhosis (F4) due to MASH.
Another promising phase 3 FGF21 analogue in development is pegozafermin, which Roche added to its developmental roster when it acquired 89bio last year.
Eli Lilly’s GLP push into MASH
Like Novo with Wegovy, Eli Lilly is pursuing a MASH approval for its massive blockbuster GLP-1, tirzepatide, the active ingredient in Mounjaro and Zepbound.
A phase 2 study of 190 MASH patients with stage 2 or 3 fibrosis showed that tirzepatide was superior to placebo for MASH resolution, with more than half of patients achieving improvement in fibrosis at 52 weeks.
However, tirzepatide is only one of the assets Lilly is pursuing in the fatty liver space.
“One I find interesting is retatrutide, a triple agonist from Eli Lilly that’s already in development for obesity and type 2 diabetes,” said Blackstock. “[With] its phase 2 data for obesity, it looks like it's going to be the best on the market if it’s approved.”
Lilly is also studying retatrutide, which targets GLP-1, GIP and glucagon receptors, for metabolic dysfunction-associated steatotic liver disease, a group of diseases of which MASH is a part.
In addition, Lilly inked a global licensing deal last year with South Korean pharma OliX Pharmaceuticals to develop and commercialize its phase 1 MASH candidate, OLX75016.
