Marea Therapeutics, a subsidiary of Lisata Therapeutics, reported that MAR001, a monoclonal antibody targeting ANGPTL4, met all objectives in Part A of the Phase 2b TYDAL-TIMI 78 trial. The results were presented as a late-breaker at the American Heart Association Scientific Sessions on November 9 and published simultaneously in the New England Journal of Medicine. The randomised, double-blind trial tested three subcutaneous doses, 300 mg, 450 mg and 900 mg every four weeks, in 235 participants in the efficacy analysis with elevated triglycerides and high remnant cholesterol, across 48 centres in the United States, Canada, Australia and New Zealand.
The primary endpoint, the placebo-adjusted change in fasting triglycerides at week 12, was a reduction of 39.1 percent to 45.5 percent across the three doses, statistically significant at every dose and sustained through week 24. The effect deepened with higher starting levels: placebo-adjusted reductions reached up to 57.2 percent in participants with baseline triglycerides of at least 300 mg/dL, and reductions from baseline, a different and unadjusted measure, reached up to 72.2 percent in those starting at 500 mg/dL or above. At the 900 mg dose, 51.7 percent of participants reached triglycerides below 150 mg/dL, against 3.4 percent on placebo.
Safety is the other half of the claim. Adverse events were reported in about 69 percent of MAR001 participants against 78 percent on placebo, serious adverse events were less frequent on the drug, there were no cases of pancreatitis, and there was no worsening of HbA1c against placebo. That glycemic neutrality is the point Endpoints picked out in its AHA coverage: up to 70 percent of people with severe hypertriglyceridemia also have type 2 diabetes, according to the company, so a triglyceride therapy that does not trade lipid control for glucose control has a defined edge to argue.
Part A was not itself a severe hypertriglyceridemia trial. Marea has begun enrolling Part B of TYDAL-TIMI 78 in participants with severe disease, and whether the antibody prevents pancreatitis, the clinical outcome that matters most in that population, remains untested.