2024 Metabolic Dysfunction-Related Non-Alcoholic Fatty Liver Disease (MASH) Therapeutic Market Emergence Research Report

Liver disease could bethe next big market MASH UP?Liver diseasecould be the nextbig market People with obesity and diabetes are athigher risk of developing fatty liverdisease. The 2024 approval of a firstdrug to treat serious forms of thiscondition unlocks another multi-billion-dollar treatment category. MASH UP? Liver disease could be the next big market (MASH), and, as the name suggests,strongly linked to obesity and diabetes -could be worth more than three timesthat. Evaluate forecasts top $9.5 billion bythe end of the decade. (The term ‘MASH’replaced non-alcoholic steatohepatitis –NASH - in 2023.) with obesity suffer from fatty liver (which,un-treated, can result in liver failure.)Some of those are now being treated withobesity medicines like Wegovy(semaglutide). Weight loss may reducethe chance of patients’ progression toMASH; Novo Nordisk’s semaglutide andEli Lilly’s tirzepatide (sold for obesity asZepbound) are both in testing for MASH. People with obesity and diabetes are at higherrisk of developing fatty liver disease. The 2024approval of a first drug to treat serious formsof this condition unlocks another multi-billion-dollar treatment category. liver scarring – fibrosis – thatcharacterises moderate to severe fattyliver disease. Sales of the drug areexpected to top $3 billion by 2030,according to Evaluate forecasts. It took decades to uncover a safe,effective obesity medicine. The path to asuccessful drug for severe fatty liverdisease been similarly long and failurestrewn. On its own, fatty liver is difficult todiagnose as it can’t be seen or felt.Diagnosis typically requires blood testsand/or a liver biopsy. Semaglutide hasn’t yet hit the mark onreducing fibrosis, but Lilly’s drug showed asignificant improvement in MASH-relatedfibrosis in a Phase 2 read-out at the EASLLiver Congress in June 2024. The revolution in obesity treatment isdragging MASH into the spotlight,however. Three quarters of people withoverweight and more than 90% of those By then, the overall therapy market for thiscondition – now known as metabolicdysfunction-associated steatohepatitis So it was a big deal when, in March 2024,Madrigal’s Rezdiffra (resmetirom) becamethe first FDA-approved treatment for the The MASH pipelineincludes over half adozen Phase 3 or Phase2 candidates coveringseveral differentmechanisms of actionbeyond incretins. Several other dual GLP-1/glucagonreceptor agonists are in the mix:Boehringer Ingelheim in 2024 reportedpositive Phase 2 fibrosis results fromsurvodutide (not yet approved for MASHor obesity) and top-line Phase 2b datafrom Altimmune’s pemvidutide isexpected in the first quarter of 2025. The MASH pipeline includes over half adozen Phase 3 or Phase 2 candidatescovering several different mechanisms ofaction beyond incretins. (See Table 1) fibrosis could soon follow obesity’sextraordinary growth trajectory. Rezdiffra is a once-daily pill which acts ona type of thyroid hormone receptorinvolved in fatty acid breakdown; Phase 3data showed improvement or stabilisationof fibrosis in 80% of patients. Viking’sVK2809, another liver-selective thyroid If Rezdiffra and its followers prove evenpartly as effective at resolving MASH asincretins are at dropping weight,medicines for fatty liver disease and Galectin Therapeutics’s belapectin inhibitsgalectin-3, a protein implicated in liverfibrosis and liver cell damage; it’s in aPhase 2b/3 trial to prevent esophagealvarices (unwanted bleeding) in MASH-associated liver cirrhosis. (Denmark-headquartered Galecto completed aPhase 1/2b trial of a similar compound in2023 before running out of cash and re-structuring.) factor 21 (FGF-21), a metabolism-relatedhormone secreted by the liver. FGF-21 hasseveral beneficial effects, includingincreasing insulin sensitivity, reducinginflammation and generally protectingliver cells from stressors including over-and under-eating. (licensed from Amgen) are similar; someanalysts suggest that Akero and 89Bio’sfibrosis data is stronger that that fromRezdiffra and tirzepatide. hormone receptor beta agonist, showedpromising Phase 2b results in June 2024;Aligos Therapeutics’ Phase 2a THR-bagonist followed suit in mid-September. But it’s early days. Fibrosis - a pathologicalversion of wound repair that featuresacross many other diseases – involves acomplex nest of cell types and signallingpathways, many of which underpinhealthy processes, too. There are multiplepotential targets but finding and hitting adisease-specific one has not been easy.Intercept’s Ocaliva (obeticholic acid), soldsince 2016 for a rare bile duct condition, isa recent MASH casualty: it received asecond FDA rebuttal in June 2023. An FGF-21-based drug isn’t a done deal,though: candidates at Eli Lilly – the first toget an FGF-21 analog into the clinic,Bristol Myers Squibb and Pfizer were alldropped. (Novo Nordisk has a once-weekly FGF-21 analog in Phase 2.) 89Bio’s pegozafermin, a long-actingFGF-21 analog, is the subject of twoglobal Phase 3 MASH