ANGPTL4 Inhibition in Adults with Elevated Triglyceride Levels.

In adults with elevated triglycerides, MAR001-mediated ANGPTL4 inhibition lowered fasting triglycerides at week 12 by placebo-adjusted least-squares changes of -39.1, -40.5, and -45.3 percentage points across 300, 450, and 900 mg doses.

• Why it matters: Elevated triglycerides are linked to cardiovascular risk, and ANGPTL4 is a regulator of triglyceride-rich lipoprotein metabolism, creating a target for pharmacologic lowering.
• What they did: In a phase 2b, double-blind, randomized, placebo-controlled trial (part A), adults with screening nonfasting triglycerides ≥175 mg/dl and remnant cholesterol ≥35 mg/dl received MAR001 300, 450, or 900 mg or placebo subcutaneously every 4 weeks for 24 weeks; the primary endpoint was placebo-adjusted percent change in fasting triglycerides at week 12.
• The result: At week 12, placebo-adjusted least-squares mean percent changes were -39.1, -40.5, and -45.3 percentage points versus placebo (P<0.001 for all comparisons), with adverse events in 69% of pooled MAR001 recipients and 78% of placebo recipients.

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