MAR001 antibody lowers triglycerides by up to 45.5% in Phase IIb trial
A Phase IIb study showed that targeting ANGPTL4 with MAR001 significantly reduces fasting triglycerides within 12 weeks.
Researchers led by the Mass General Brigham Heart and Vascular Institute found that the monoclonal antibody MAR001 significantly reduces fasting triglyceride levels in patients with hypertriglyceridemia, as reported by news-medical.net. The Phase IIb trial evaluated 235 participants across 48 clinical centers in the United States, Canada, Australia, and New Zealand. Participants received subcutaneous injections of either a placebo or MAR001 at doses of 300, 450, or 900 mg every four weeks for 24 weeks news-medical.net
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Mechanism of action and trial results
Unlike conventional lipid-lowering drugs, MAR001 targets ANGPTL4, a protein that acts as an endogenous inhibitor of lipoprotein lipase, the primary enzyme responsible for hydrolyzing circulating triglycerides. By blocking ANGPTL4, the antibody promotes triglyceride clearance. At week 12, the drug demonstrated a statistically significant, placebo-adjusted reduction in fasting triglycerides ranging from 39.1% to 45.5% across all three dose cohorts.
Investigators reported that MAR001 did not lead to an increase in adverse events compared to the placebo group. Greater relative reductions in triglycerides were documented in participants who presented with higher baseline levels prior to treatment initiation.
Next steps and clinical implications
The study was developed by the Mass General Brigham Thrombolysis in Myocardial Infarction (TIMI) Study Group in collaboration with Marea Therapeutics, with findings published in the New England Journal of Medicine and presented at the American Heart Association annual meeting news-medical.net
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Further research is required to evaluate the long-term safety profile and determine whether sustained reductions in triglyceride levels correlate with lower risks of acute pancreatitis and cardiovascular complications. The investigative team plans to evaluate MAR001 in a follow-up trial specifically focused on patients with severely elevated triglyceride levels.
