PCSK9 inhibition
AMG145 (evolocumab) cuts Lp(a) by up to 32% in statin-treated patients, the LAPLACE-TIMI 57 phase 2 trial of 631 patients (Circulation 2013)
Original title: AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9, significantly reduces lipoprotein(a) in hypercholesterolemic patients receiving statin therapy: an analysis from the LDL-C Assessment with Proprotein Convertase Subtilisin Kexin Type 9 Monoclonal Antibody Inhibition Combined with Statin Therapy (LAPLACE)-Thrombolysis in Myocardial Infarction (TIMI) 57 trial
As part of the LAPLACE-TIMI 57 trial, 631 hypercholesterolaemic patients on statin therapy were randomised to AMG145 (a PCSK9 monoclonal antibody, later named evolocumab) at one of three doses every 2 or 4 weeks, or placebo, with Lp(a) measured at baseline and week 12. Compared with placebo, AMG145 70, 105, and 140 mg every 2 weeks reduced Lp(a) by 18%, 32%, and 32% (all P<0.001), and 280, 350, and 420 mg every 4 weeks reduced Lp(a) by 18%, 23%, and 23% (all P<0.001). Lp(a) reduction correlated with LDL cholesterol reduction (rho=0.33, P<0.001), and the effect was consistent regardless of age, sex, race, diabetes history, or background statin regimen, though patients with higher baseline Lp(a) had larger absolute but smaller percent reductions. The findings show AMG145 significantly reduces Lp(a) by up to 32%, offering a benefit beyond its established LDL cholesterol-lowering effect.
Original abstract
Background: Lipoprotein(a) [Lp(a)] is an emerging risk factor for cardiovascular disease. Currently, there are few available therapies to lower Lp(a). We sought to evaluate the impact of AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), on Lp(a).
Methods And Results: As part of the LDL-C Assessment With PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy (LAPLACE)-Thrombolysis in Myocardial Infarction (TIMI) 57 trial, 631 patients with hypercholesterolemia receiving statin therapy were randomized to receive AMG145 at 1 of 3 different doses every 2 weeks or 1 of 3 different doses every 4 weeks versus placebo. Lp(a) and other lipid parameters were measured at baseline and at week 12. Compared with placebo, AMG145 70 mg, 105 mg, and 140 mg every 2 weeks reduced Lp(a) at 12 weeks by 18%, 32%, and 32%, respectively (P<0.001 for each dose versus placebo). Likewise, AMG145 280 mg, 350 mg, and 420 mg every 4 weeks reduced Lp(a) by 18%, 23%, and 23%, respectively (P<0.001 for each dose versus placebo). The reduction in Lp(a) correlated with the reduction in low-density lipoprotein cholesterol (ρ=0.33, P<0.001). The effect of AMG145 on Lp(a) was consistent regardless of age, sex, race, history of diabetes mellitus, and background statin regimen. Patients with higher levels of Lp(a) at baseline had larger absolute reductions but comparatively smaller percent reductions in Lp(a) with AMG145 compared with those with lower baseline Lp(a) values.
Conclusions: AMG145 significantly reduces Lp(a), by up to 32%, among subjects with hypercholesterolemia receiving statin therapy, offering an additional, complementary benefit beyond robust low-density lipoprotein cholesterol reduction with regard to a patient's atherogenic lipid profile.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.