Inhibition of angiopoietin-like protein 4 (ANGPTL4) with the monoclonal antibody MAR001 significantly reduced fasting triglyceride levels at 12 weeks, based on findings from the TYDAL-TIMI 78 trial presented at AHA 2026 and simultaneously published in NEJM.

The two-part, phase 2b, double-blind trial involved 236 adults (mean age 60 years and 39% women) with non-fasting triglyceride levels of at least 175 mg per deciliter and remnant cholesterol levels of at least 35 mg per deciliter at initial screening, followed by fasting triglyceride levels of at least 150 mg per deciliter and remnant cholesterol levels of at least 30 mg per deciliter on confirmatory screening. Participants were randomly assigned to receive MAR001 at a dose of 300 mg, 450 mg or 900 mg or matching placebo subcutaneously every 4 weeks for 24 weeks.

The primary endpoint looking at the placebo-adjusted least-squares mean percent changes in fasting triglyceride levels from baseline to week 12, were −39.1 percentage points, −40.5 percentage points, and −45.3 percentage points for those receiving MAR001 at 300 mg, 450 mg, and 900 mg doses, respectively. Adverse events were reported in 69% of those assigned to MAR001 and 78% of those receiving placebo.

"The magnitude of triglyceride lowering appeared to be more pronounced among participants with higher baseline levels than among those with lower baseline levels," said Michelle L. O'Donoghue, MD, FACC, et al. "Treatment did not lead to adverse changes in glucose homeostasis markers or aminotransferase levels or to excess injection-site reactions."

Commenting on the results, Renuka Jain, MD, FACC, noted that there's still more to learn. "We need longer-term studies in more diverse populations to determine whether these reductions are sustained and to better understand clinical outcomes and the effects of prolonged treatment," she said.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Novel Agents

Keywords: AHA Annual Scientific Sessions, AHA26, Angiopoietin-like 4 Protein, Antibodies, Monoclonal, Triglycerides, Cholesterol