Alirocumab, a Fully Human Monoclonal Antibody to Proprotein Convertase Subtilisin/kexin Type 9, and Its Effects on Lipoprotein Subfractions Determined by Ion Mobility

Background: A causative role for low-density lipoproteins (LDLs) in the development of atherosclerotic cardiovascular disease (CVD) has been established, with randomized studies showing that LDL cholesterol (LDL-C) lowering reduces CVD events. Studies also indicate a stronger association between LDL particle concentrations and CVD risk than LDL-C alone. Ion mobility provides direct measurements of particle concentrations of LDL, very-low density (VLDL), intermediate-density (IDL) and high-density (HDL) lipoproteins and may demonstrate effects of lipid modifying drugs not revealed by standard lipid profiles. Methods: A Phase 2 randomized, double-blind, clinical trial (NCT01288443) was conducted in patients with hypercholesterolemia and LDL-C levels ≥100mg/dL on stable atorvastatin (10-40 mg daily). In this substudy, we evaluated 31 patients who received placebo with 27 patients who received alirocumab 150 mg every 2 weeks (Q2W) via a 1-mL subcutaneous injection and compared lipoprotein subfractions measured using ion mobility at baseline and Week 12. Results: The table shows changes in lipids from the Phase 2 study, and lipoprotein subfractions from this substudy, in placebo and alirocumab 150 mg Q2W groups from baseline to Week 12. Compared with placebo, alirocumab on average, reduced per person VLDL concentration by 39.9% (p Conclusion: Alirocumab significantly reduced levels of all LDL, IDL and VLDL particle subfractions as measured by ion mobility consistent with its published effect on LDL-C.