Abstract 19133: Inhibition of ANGPTL3 by Evinacumab Reduced Triglycerides (TGs) and LDL-C in Subjects Presenting With Modest Elevations in TGs and/or LDL-C, Recapitulating the Hypolipidemic Effects of Loss-of-Function (LoF) Mutations of ANGPTL3

Introduction: Elevations in LDL-C and TGs have been linked to increased CHD risk. Angiopoietin-like 3 (ANGPTL3) has a central role in lipid metabolism, and LoF mutations of ANGPTL3 in humans have been associated with reductions in TGs, LDL-C and HDL-C. Evinacumab (REGN1500) is a human monoclonal antibody specific for ANGPTL3 being developed for treatment of hyperlipidemia, including hypertriglyceridemia and hypercholesterolemia. Methods: This phase 1, first-in-human, ascending single-dose, placebo (PBO)-controlled, double-blind study evaluated the safety and efficacy of evinacumab administered subcutaneously (SC) or intravenously (IV) in subjects with elevated TGs (150≤ TG ≤450 mg/dL) and/or LDL-C (≥100 mg/dL). The first part of the study randomized subjects to PBO (9, PBO SC; 12, PBO IV) and evinacumab (11, 75 mg SC; 12, 150 mg SC; 9, 250 mg SC; 10, 5 mg/kg IV; 9, 10 mg/kg IV; 11, 20 mg/kg IV). Results: Evinacumab was well tolerated in this trial. Forty-one subjects reported at least one treatment emerge...