At a Glance
- The new drug ION224 is a promising treatment for MASH, a severe form of fatty liver disease linked to obesity and type 2 diabetes.
- It works by inhibiting a liver enzyme called DGAT2, which is crucial for fat production, thereby reducing the liver inflammation and injury that define the disease.
- In a Phase 2 trial, nearly 60% of patients receiving the highest dose showed significant improvements in liver health compared to those who took a placebo.
- The medication was safe, and its positive effects occurred independently of changes in a patient’s body weight, suggesting it can be combined with other therapies.
- Researchers are now planning larger Phase 3 trials to confirm these findings and move closer to offering a targeted therapy for millions affected by MASH.
Researchers have identified a new investigational drug that successfully treats a severe form of fatty liver disease, according to a study recently published in The Lancet. The drug, ION224, offers hope for patients with metabolic dysfunction-associated steatohepatitis, or MASH, a condition linked to obesity and type 2 diabetes that can lead to irreversible liver failure. In a mid-stage clinical trial, the treatment significantly reduced liver fat, inflammation, and cellular injury, marking a significant step forward in addressing the disease.
The new therapy targets a specific enzyme in the liver, known as diacylglycerol O-acyltransferase 2 (DGAT2). This enzyme plays a central role in de novo lipogenesis, the metabolic process by which the body creates and stores fat in the liver. By using an antisense inhibitor—a type of drug designed to block the production of a specific protein—ION224 effectively suppresses DGAT2. This action interrupts the disease at its source, preventing the fat accumulation and inflammation that drive liver damage in MASH patients.
The Phase 2 trial, led by researchers at the University of California, San Diego School of Medicine, included 160 adults with MASH and liver scarring, known as fibrosis. Over the course of one year, participants received monthly injections of ION224 at various doses or a placebo. The results were compelling: nearly 60% of patients on the highest dose experienced significant histological improvements in their liver health. Notably, these benefits were observed without any corresponding weight loss, suggesting the drug could be combined with other treatments.
These findings position ION224 as a promising targeted therapy for a condition that affects millions and often progresses silently until it reaches life-threatening stages. “This is the first drug of its kind to show real biological impact in MASH,” said Dr. Rohit Loomba, the study’s principal investigator, in a university press release. He added that if the results are confirmed in larger, Phase 3 trials, the drug could halt or even reverse liver damage. Researchers are now planning these larger trials to bring the treatment closer to widespread availability.
References
- Loomba, R., Morgan, E., Yousefi, K., Li, D., Geary, R., Bhanot, S., & Alkhouri, N. (2025). Antisense oligonucleotide DGAT-2 inhibitor, ION224, for metabolic dysfunction-associated steatohepatitis (Ion224-cs2): Results of a 51-week, multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet, 406(10505), 821–831. https://doi.org/10.1016/S0140-6736(25)00979-1
- University of California-San Diego. (2025, August 27). First enzyme-targeting drug reverses damage in metabolic fatty liver disease. Medical Xpress; University of California-San Diego. https://medicalxpress.com/news/2025-08-enzyme-drug-reverses-metabolic-fatty.html
