Key Points:
- ION224 cuts liver fat and inflammation
- 60% patients improved in trials
- Potential first targeted MASH therapy
Investigational therapy targets fat production and inflammation in the liver with encouraging early results. A newly developed investigational drug may offer hope to millions of people living with advanced fatty liver disease, according to findings from researchers at the University of California, San Diego School of Medicine. The treatment directly targets fat production in the liver, addressing the underlying drivers of the condition rather than just its symptoms.
Metabolic dysfunction-associated steatohepatitis (MASH), previously known as nonalcoholic steatohepatitis (NASH), is a severe form of fatty liver disease tied to obesity and type 2 diabetes. Left untreated, it can progress to cirrhosis, liver failure, or liver cancer. The condition is often called a “silent disease” because it can develop without obvious warning signs for years.
The Phase IIb clinical trial results, published in The Lancet, reveal that the experimental drug ION224 significantly reduced fat accumulation and inflammation in the liver—two critical factors driving progression of MASH.
Blocking fat accumulation and liver inflammation
The investigational drug works by inhibiting an enzyme known as DGAT2, which plays a central role in the liver’s process of producing and storing fat. By blocking this pathway, researchers observed improvements in liver health, even without major changes in body weight.
“This study marks a pivotal advance in the fight against MASH,” said Dr. Rohit Loomba, principal investigator and chief of the Division of Gastroenterology and Hepatology at UC San Diego School of Medicine. “By blocking DGAT2, we’re interrupting the disease process at its root cause, stopping fat accumulation and inflammation right in the liver.”
The year-long study enrolled 160 adults across the United States who had been diagnosed with MASH and showed signs of early to moderate fibrosis. Participants received monthly injections of either the investigational therapy or a placebo. At the highest dose, 60 percent of patients treated with ION224 experienced significant liver improvements compared to those in the placebo group.
Notably, the treatment’s benefits appeared regardless of weight changes, suggesting that it could complement other lifestyle or medical interventions. Importantly, researchers reported no serious side effects linked to the drug.
A widespread and silent condition
MASH is one of the most common chronic liver diseases worldwide. In the United States alone, more than 100 million people are believed to have some form of fatty liver disease. Globally, as many as one in four adults may be affected. Despite its prevalence, few treatment options exist today, and many patients remain undiagnosed until the disease has advanced.
Because the condition often progresses quietly, individuals may not realize they are at risk until irreversible damage has occurred. When left untreated, MASH can lead to liver transplantation as the only option for survival. The economic burden of treating advanced liver disease also places a significant strain on health care systems.
“This is the first drug of its kind to show real biological impact in MASH,” Loomba said. “If these findings are confirmed in larger Phase III trials, we may finally be able to offer patients a targeted therapy that halts and potentially reverses liver damage before it becomes life-threatening.”
Looking ahead to future therapies
Researchers emphasize that while the results are promising, further study is essential before the treatment can be approved for widespread use. Larger clinical trials are already being planned to confirm both safety and effectiveness across more diverse patient populations.
Loomba, who also directs the Metabolically Dysregulated-Associated Steatotic Liver Disease (MASLD) Research Center at UC San Diego School of Medicine, stressed the importance of advancing therapies that directly address the biological roots of liver disease. Early intervention, he said, could save lives while also reducing the need for costly procedures like transplants.
For patients and families affected by fatty liver disease, these findings bring renewed optimism. If future trials confirm the results, ION224 could represent the first truly targeted treatment for MASH, offering a potential turning point in the management of a condition that has long lacked effective therapies.
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