Abstract 17492: Alirocumab, a Proprotein Convertase Subtilisin/Kexin Type 9 Monoclonal Antibody, Reduces Cholesterol Concentrations of Serum Remnant Lipoprotein Fractions, Very Low-Density Lipoproteins and Triglycerides
Introduction: Increased very low-density lipoprotein (VLDL) levels form part of a pattern of atherogenic dyslipidemia which predisposes to premature atherosclerosis. Remnant lipoproteins are products of VLDL lipolysis, and include VLDL3 and intermediate-density lipoproteins (IDL, the direct precursor to LDL formation).
Hypothesis: Alirocumab reduces serum levels of VLDL and lipoprotein remnants, contributing to its ability to reduce serum LDL-C and non-HDL-C.
Methods: Three phase 2, placebo-controlled trials were conducted on patients with either primary hypercholesterolemia (565 [NCT01288443], n=183; 566 [NCT01288469], n=92) or heterozygous familial hypercholesterolemia (1003 [NCT01266876], n=77). Patients on background statins+/-ezetimibe received alirocumab 50-300 mg administered subcutaneously every 2 or 4 weeks (Q2W, Q4W), depending on the study, providing reductions in mean LDL-C of up to 72.4%. In post hoc analyses, lipoproteins were subfractionated by vertical auto profile (VAP) testing. Percent changes in VLDL-C, VLDL1+2-C (a measure of cholesterol in "large, buoyant" VLDL particles), triglycerides (TG), VLDL3-C, IDL-C and total remnant lipoprotein cholesterol levels (RLP-C; VLDL3-C + IDL-C) in patients treated with alirocumab 150 mg Q2W (a dose common to all 3 trials) vs. placebo were analyzed at week 12 (565), week 8 (566) and week 6 (1003) using ANCOVA.
Results: In the 3 studies, reductions in TG, VLDL-C, and in the cholesterol content of remnant lipoprotein were observed with alirocumab vs. placebo (Table). Treatment-emergent adverse events (TEAEs) occurred in 54.5% with placebo vs. 58.3% of patients receiving alirocumab 150 mg Q2W. The most common TEAEs were injection site reactions, typically of mild intensity and short duration.
Conclusions: Alirocumab reduced serum TG and VLDL-C, in addition to reducing cholesterol concentrations of remnant lipoprotein fractions separable by VAP, including VLDL3-C and IDL-C.
- © 2013 by American Heart Association, Inc.