AMG 145, A Monoclonal Antibody Against PCSK9, Significantly Reduces Lipoprotein (a) in Hypercholesterolemic Patients Receiving Statin Therapy: An Analysis From the LAPLACE-TIMI 57 Trial
Background—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 AMG 145, a monoclonal antibody against PCSK9, on Lp(a).
Methods and Results—As part of the LAPLACE-TIMI 57 trial, 631 patients with hypercholesterolemia receiving statin therapy were randomized to receive AMG 145 at one of 3 different doses every 2 weeks or one of 3 different doses every 4 weeks versus placebo. Lp(a) and other lipid parameters were measured at baseline and at week 12. As compared with placebo, AMG 145 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 vs. placebo). Likewise, AMG 145 280 mg, 350 mg, and 420 mg every 4 weeks reduced Lp(a) by 18%, 23%, and 23% respectively (P<0.001 for each dose vs. placebo). The reduction in Lp(a) correlated with the reduction in LDL-C (ρ=0.33, P<0.001). The effect of AMG 145 on Lp(a) was consistent regardless of age, gender, race, history of diabetes, and background statin regimen. Patients with higher levels of Lp(a) at baseline had larger absolute reductions but comparatively smaller percentage reductions in Lp(a) with AMG 145 compared to those with lower baseline Lp(a) values.
Conclusions—AMG 145 significantly reduces Lp(a), by up to 32%, among subjects with hypercholesterolemia receiving statin therapy, offering an additional, complementary benefit beyond robust LDL-C reduction with regard to a patient's atherogenic lipid profile.
Clinical Trial Registration Information—http://clinicaltrials.gov/. Identifier: NCT01380730.
- Received March 1, 2013.
- Revision received June 28, 2013.
- Accepted July 12, 2013.