Abstract 18390: Effects of a Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9) Inhibitor, Alirocumab, on Lipid and Lipoprotein Metabolism in Healthy Subjects

Background: Alirocumab is a monoclonal antibody that inhibits binding of PCSK9 to LDL receptors, decreasing their lysosomal degradation and increasing their numbers on cell surfaces. In Phase 2/3 studies, alirocumab 150 mg lowered LDL-cholesterol (C) ~61%, apoB 53%, and fasting triglycerides (TG) 16%. The mechanisms that increased LDL removal or the effects on postprandial (PP) TG levels after alirocumab therapy have not been reported. Method: 18 (10F, 8 M), healthy volunteers completed a Phase 1, placebo-controlled, single-blind, single-sequence study. Subjects received 2 placebo doses followed by 5 alirocumab doses, 150 mg SC every 2 wks. At the end of each treatment period, we measured fasting lipids and lipoproteins and subjects received a high fat meal with PP TG and apoB48 levels measured over 8hrs. Stable isotope studies were performed 3-5 days later to measure apoB turnover in very low density (VLDL), intermediate density (IDL) and LDL. Results: In 18 subjects, Alirocumab significantly reduced pla...