AASLD-INASL Joint Webinar: Advances in MASH Diagnosis and Treatment (ondemand)-Pharmacological Breakthroughs in MASH

Pharmacological Breakthroughs in MASH

Pdf Summary

This presentation reviews major pharmacological advances in MASH (metabolic dysfunction-associated steatohepatitis), emphasizing that lifestyle change remains foundational but is often insufficient alone. Recommended nonpharmacologic measures include calorie reduction, weight loss, exercise, a Mediterranean-style diet, avoiding sugar-sweetened beverages and heavy alcohol, limiting fructose, and considering bariatric surgery in appropriate patients.  <br /><br />The talk then highlights a rapidly expanding drug pipeline targeting multiple pathways involved in MASH, including lipotoxicity, inflammation, fibrosis, and metabolic regulation. Agents in phase 3 development include resmetirom, semaglutide, lanifibranor, efruxifermin, pegozafermin, survodutide, and tirzepatide.  <br /><br />Several trial results are summarized. Resmetirom, a THR-β agonist, showed significant benefits in the MAESTRO-NASH trial, improving both MASH resolution and fibrosis endpoints. Pegozafermin and efruxifermin, both FGF21-based therapies, also demonstrated meaningful improvements in fibrosis and MASH resolution in phase 2/3 studies. Semaglutide showed favorable effects in phase 3, with improved rates of MASH resolution and fibrosis response. Survodutide and tirzepatide, both incretin-based therapies, likewise produced strong histologic and metabolic improvements. Lanifibranor and the liver-directed DGAT-2 antisense inhibitor ION224 also showed promising efficacy signals in earlier trials.  <br /><br />The key clinical message is that FDA-approved pharmacotherapy for at-risk MASH is now available, specifically for noncirrhotic patients with moderate-to-advanced fibrosis (F2–F3). The slide deck states that resmetirom and semaglutide are FDA approved for this population, and many additional therapies remain in development.

Keywords

MASH

metabolic dysfunction-associated steatohepatitis

lifestyle modification

resmetirom

semaglutide

fibrosis

MASH resolution

FGF21 therapies

phase 3 trials

FDA-approved pharmacotherapy