A 45.5% Drop in Fasting Triglycerides
A single injection of the monoclonal antibody MAR001 has triggered a sharp decline in fasting triglyceride levels, with clinical data showing a reduction of up to 45.5% within 12 weeks.
The findings, published in the New England Journal of Medicine, point to a potential shift in how clinicians manage stubborn lipid levels that resist traditional interventions.
The phase 2b trial, overseen by the Mass General Brigham Heart and Vascular Institute, tracked 235 participants across the United States, Canada, Australia, and New Zealand. Over the study period, subjects received subcutaneous injections of either MAR001 or a placebo every four weeks.
Disrupting the ANGPTL4 Pathway
At the heart of the therapy is the inhibition of the ANGPTL4 protein, which normally acts as a biological brake, preventing lipoprotein lipase from breaking down triglycerides. By neutralizing this protein, MAR001 appears to clear lipids from the blood more efficiently.
“Despite advances in lipid-lowering therapy, many patients continue to have elevated triglyceride levels and cardiovascular risk,” said lead author Michelle O’Donoghue, a cardiologist with the Mass General Brigham Heart and Vascular Institute. “Our findings suggest that MAR001 may be able to safely and effectively lower triglycerides.”
Triglycerides Drop Significantly at Three Dosage Levels
Researchers tested three distinct dosage levels, recording placebo-adjusted reductions in fasting triglycerides between 39.1% and 45.5% at the 12-week mark. The incidence of adverse effects in the MAR001 group was comparable to those observed in the placebo group, suggesting the drug is safe in these initial stages.
Competing Investigational Approaches
Many experimental candidates are currently competing in lipid management. At the American Heart Association’s Scientific Sessions 2025, researchers unveiled data on DR10624, an investigational drug that acts on three distinct receptors: FGF21, glucagon, and GLP-1. In a trial involving 79 adults, DR10624 achieved a triglyceride reduction exceeding 60%.
While MAR001 focuses on the ANGPTL4 pathway, DR10624 has also shown promise in metabolic health, reporting a 63% reduction in liver fat. Both treatments remain in the investigative phase, with long-term safety data still required to validate these early results.
The research team at Mass General Brigham is now preparing a follow-up study to focus on patients with severely elevated triglyceride levels. According to O’Donoghue, the data showed that “we observed greater reductions in triglycerides in participants with higher baseline triglyceride levels.” Future trials will aim to determine whether these lipid reductions ultimately decrease the risk of serious complications, such as pancreatitis.
MAR001 Targets ANGPTL4 Protein to Treat Elevated Triglycerides
Elevated triglycerides are a clinical concern linked to cardiovascular disease, fatty buildup in artery walls, and inflammation of the pancreas. While traditional therapies include statins and fibrates, MAR001 targets the ANGPTL4 protein using monoclonal antibodies. Both MAR001 and DR10624 are currently in intermediate development stages, and further research is necessary to confirm their efficacy before they are considered for broader clinical use.
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