AMG 145, a monoclonal antibody against PCSK9, facilitates achievement of national cholesterol education program-adult treatment panel III low-density lipoprotein cholesterol goals among high-risk patients: an analysis from the LAPLACE-TIMI 57 trial (LDL-C assessment with PCSK9 monoclonal antibody inhibition combined with statin thErapy-thrombolysis in myocardial infarction 57)

Abstract

Objectives: This study sought to define the ability of AMG 145, a monoclonal antibody directed against proprotein convertase subtilisin kexin type 9 (PCSK9), to enable subjects at high risk for major adverse cardiovascular events to achieve National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) parameters for low-density lipoprotein cholesterol (LDL-C) and other lipid goals.

Background: Many patients at high risk for adverse cardiovascular events are unable to achieve the NCEP-ATP III LDL-C goal of <70 mg/dl, even with high-potency statin therapy.

Methods: In 282 subjects from the LAPLACE-TIMI 57 (LDL-C Assessment with PCSK9 monoclonaL Antibody Inhibition Combined With Statin thErapy-Thrombolysis In Myocardial Infarction 57) trial at high risk according to NCEP-ATP III criteria, we compared the proportion of subjects achieving the NCEP-ATP III recommended LDL-C goal of <70 mg/dl across treatment arms. Other outcomes included the triple goals of LDL-C <70 mg/dl, non-high-density lipoprotein cholesterol (HDL-C) <100 mg/dl, and apolipoprotein B (ApoB) <80 mg/dl.

Results: During the dosing interval, more than 90% of subjects in both of the top dose groups every 2 weeks and every 4 weeks attained this lipid target over the dosing interval, with similar success rates for the triple lipid goal.

Conclusions: PCSK9 inhibition with AMG 145 enables high-risk patients to achieve established lipid goals. If this therapy demonstrates efficacy for reducing cardiovascular events with a favorable safety profile in ongoing phase 3 trials, we believe it will have major public health implications.

Keywords: ApoB; CAD; CHD; CV; HDL-C; LDL; LDL-C; NCEP-ATP III; NHANES; National Cholesterol Education Program-Adult Treatment Panel III; National Health and Nutrition Examination Survey; PCSK9; UC; ULN; apolipoprotein B; cardiovascular; cholesterol; coronary artery disease; coronary heart disease; high-density lipoprotein cholesterol; low-density lipoprotein cholesterol; statins; ultracentrifugation; upper limit of normal.