Focusing on GLP-1 receptors now has the FDA’s blessing as a approach to deal with the fatty liver illness referred to as MASH with Novo Nordisk’s weekly injectable drug Wegovy turning into the second authorized remedy for this prevalent metabolic dysfunction.
In MASH, brief for metabolic dysfunction-associated steatohepatitis, the buildup of fats within the liver results in irritation and scarring of the organ, which is named fibrosis. The FDA’s late Friday regulatory determination for Wegovy covers the remedy of adults whose MASH has led to moderate-to-severe fibrosis. These sufferers should not have MASH that has progressed to liver cirrhosis, essentially the most superior stage of the illness. Like its earlier approval in weight problems, Wegovy’s MASH approval covers use of the drug alongside eating regimen and train.
The energetic ingredient in Wegovy is semaglutide, a peptide engineered to focus on and activate GLP-1 receptors within the intestine. This strategy promotes satiety and delays gastric emptying, serving to sufferers really feel full so that they eat much less. This mechanism of motion supported the drug’s preliminary approval in weight problems. The way in which Wegovy works to deal with MASH is just not totally understood, however lowering physique fats is assumed to contribute to liver profit. Approval of the two.4 mg dose of Wegovy in MASH relies on interim outcomes from a placebo-controlled Part 3 scientific trial evaluating 1,197 sufferers with moderate-to-severe MASH. At week 72, leads to 800 trial individuals confirmed 63% achieved MASH decision and no worsening of fibrosis, a purpose achieved by 34% of these within the placebo arm.
The regulatory determination for Wegovy in MASH is an accelerated approval primarily based on the interim outcomes at 72 weeks. That profit have to be confirmed by the continued Part 3 trial. Investigators will look to see whether or not the irritation and scarring enhancements noticed on the interim 72-week mark translate into decreases in demise, liver transplants, and different liver-related occasions measured at 240 weeks.
Wegovy was authorized for treating weight problems in 2021. Final 12 months, the drug expanded its U.S. and European approvals to incorporate lowering the chance of heart problems, coronary heart assault, and stroke in adults with weight problems or obese. Throughout all of Wegovy’s authorized makes use of, Novo Nordisk reported greater than 36.8 billion Danish krone (about $5.7 billion) in gross sales within the first half of this 12 months.
“The FDA’s conditional approval of Wegovy for the remedy of adults with noncirrhotic MASH marks a really pivotal milestone and a big step ahead for the MASH group and people searching for new choices,” Dave Moore, Novo Nordisk’s govt vp of U.S. Operations stated in a ready assertion.
With its newest FDA approval, Wegovy will now compete in opposition to Rezdiffra, the Madrigal Prescribed drugs drug whose accelerated approval final 12 months made it the primary MASH drug. The small molecule, formulated as a once-daily capsule, works by focusing on and activating a receptor within the liver referred to as thyroid hormone receptor beta (THR-beta), mediating metabolic exercise within the organ. In Madrigal’s report of second quarter 2025 monetary outcomes, the corporate stated Rezdiffra accounted for greater than $350 million in income within the first half of this 12 months.
In a word despatched to traders Saturday, Leerink Companions analyst Thomas Smith stated that whereas his agency believes medication like Wegovy will discover use treating some features of MASH, the agency expects drug mixtures spanning a number of drug courses will turn out to be the usual of look after this illness. Based mostly on discussions with clinicians, Smith stated Leerink expects incretin mimetics, together with Wegovy, are more likely to be most well-liked for brand spanking new MASH sufferers who’ve metabolic traits of the illness, reminiscent of weight problems and heart problems, and who will not be at the moment receiving treatment to handle these comorbidities.
Leerink nonetheless tasks robust market uptake for Rezdiffra, with the Madrigal drug being most well-liked for sufferers who’re already taking a GLP-1 agonist. The agency notes that about 25% of sufferers taking Rezdiffra are additionally at the moment taking a GLP-1 drug and half of sufferers have tried a GLP-1 drug previously.
One other issue is the rising use of Eli Lilly’s tirzepatide, the GLP-1- and GIP receptor-targeting peptide marketed as Mounjaro for kind 2 diabetes and as Zepbound for weight administration. Smith stated it’s unlikely a doctor will change a affected person already taking one among these Lilly medication to Novo Nordisk’s product merely due to its MASH approval. For these sufferers, Rezdiffra could be the drug of selection added on prime of tirzepatide. That stated, Lilly is getting ready to advance to Part 3 assessments in MASH with tirzepatide and retatrutide, a peptide engineered to go after three targets.
For a few years, MASH (previously often known as non-alcoholic steatohepatitis, or NASH) was a tricky indication for drug builders. Genfit and Intercept Prescribed drugs are among the many biotechs that encountered scientific trial and regulatory setbacks within the metabolic illness. However Leerink’s Smith says the FDA nod for Wegovy in MASH, with a label in step with the drug’s scientific trial expertise, bolsters confidence within the accelerated approval pathway for this indication. Leerink sees the newest Wegovy approval having optimistic readthrough to different medication in late-stage improvement for MASH.
Akero Therapeutics is at the moment in Part 3 testing with efruxifermin, a fusion protein engineered to imitate FGF21, a protein within the physique referred to as that regulates vitality expenditure and fats metabolization. The biotech has already reported Part 2 outcomes displaying this once-weekly injection met trial objectives displaying enchancment on measures of MASH at 96 weeks. Extra detailed outcomes had been printed final week within the journal The Lancet. 89bio can be in Part 3 testing with pegozafermin, an engineered model of FGF21. Sagimet Biosciences takes a unique strategy with denifanstat, an oral small molecule inhibitor of fatty acid synthase (FASN).
“Shifting ahead, we’re inspired with FDA’s label consistency, well timed nature of accelerated approvals, and more and more progressive views on noninvasive assessments (NITs) —all of that are remodeling the perceived issue of the regulatory path, in addition to the scientific and industrial MASH panorama,” Smith stated.
Photograph: Michael Siluk/UCG/Common Pictures Group, through Getty Pictures
