Abstract 16955: Effects of Evolocumab (AMG 145) as a Monotherapy or in Combination with Statins on Lipoprotein Particles and Subclasses

Abstract

Background: Evolocumab (AMG 145) reduces LDL-C alone or in combination with statins. We evaluated the effect of evolocumab on lipoprotein particles from subjects receiving evolocumab as monotherapy or combined with statins using biomarker samples collected from 2 clinical studies. Methods: Exploratory biomarker samples, taken before and after evolocumab treatment from a phase 1b study evaluating evolocumab combined with statins in hypercholesterolemic (HCL) subjects and from a phase 2 study evaluating evolocumab as a monotherapy in HCL subjects, were analyzed by NMR at LipoScience, Inc. Lipoprotein particle concentrations and size were determined using the LP-3 module. Results: Evolocumab alone or in combination with statins significantly reduced total, small, and large LDL-P in a dose-dependent manner. As shown in the table, evolocumab monotherapy reduced total LDL-P by 45% and 54%, small LDL-P by 36% and 35%, and large LDL-P by 68% and 84%, after 140 mg and 420 mg doses, respectively. LDL-P values were reduced slightly less than LDL-C (52% at 140 mg and 62% at 420 mg), but LDL-P reductions were similar to those seen for ApoB. IDL-P, total VLDL-P, and small VLDL-P were also reduced. Total HDL-P increased, primarily due to increases in large HDL-P. Similar results were obtained when evolocumab was given combined with statins, but with greater reductions in total, small, and large LDL-P. Notably, greater reductions in LDL-P or LDL-C were correlated with higher concentrations of total LDL-P, small LDL-P, triglycerides, smaller LDL size, and lower HDL-C at baseline. Conclusion: Evolocumab either alone or in combination with statins affected lipoprotein particles similarly. In both treatment regimens, LDL-C and total LDL-P were significantly reduced and large LDL-P were reduced, on average, to a greater extent than small LDL-P. Total LDL-P was reduced to a lesser extent than LDL-C. Additionally, reductions in VLDL-P and IDL-P were observed along with increases in HDL-P.