New Drug Stops Fatty Liver Damage in Clinical Trial - Video

A new investigational drug targeting the root cause of metabolic dysfunction-associated steatohepatitis (MASH) has shown promising results in a clinical trial led by researchers at the University of California San Diego School of Medicine. The findings, published in the online edition of The Lancet, offer new hope for patients suffering from this serious form of fatty liver disease, which affects millions globally and can lead to cirrhosis, liver failure, and liver cancer.

The study evaluated a novel medication known as ION224, which works by inhibiting DGAT2, a liver enzyme responsible for fat production and storage. By blocking DGAT2, the drug aims to reduce both fat buildup and inflammation—two major contributors to liver damage in MASH.

In the Phase IIb clinical trial, 160 adults with biopsy- confirmed MASH and early to moderate fibrosis received monthly injections of ION224 at varying doses or a placebo over a year. The results were compelling: at the highest dose, 60% of participants showed significant liver health improvement compared to the placebo group. Importantly, the effects were independent of weight loss, suggesting the drug could complement other treatments. No serious side effects linked to the drug were reported.

Often called a "silent" disease, MASH can progress undetected for years. More than 100 million Americans are estimated to have some form of fatty liver disease, with up to 1 in 4 adults worldwide affected.

"This is the first drug of its kind to show real biological impact in MASH," said Dr. Rohit Loomba, principal investigator and chief of the Division of Gastroenterology and Hepatology at UC San Diego School of Medicine. "If these findings are confirmed in Phase III trials, we may finally be able to offer patients a targeted therapy that halts and potentially reverses liver damage before it progresses to life-threatening stages."

Loomba emphasized the importance of early intervention to not only improve patient outcomes but also reduce long-term burdens on healthcare systems. The research team now plans to move forward with larger clinical trials to bring the therapy closer to regulatory approval and patient access.

Reference: Rohit Loomba, Erin Morgan, Keyvan Yousefi, Dan Li, Richard Geary, Sanjay Bhanot, Naim Alkhouri. 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, 2025; 406 (10505): 821 DOI: 10.1016/S0140-6736(25)00979-1