Evolocumab (AMG 145) for primary hypercholesterolemia.

Evolocumab is a fully human monoclonal IgG2 antibody that inhibits proprotein convertase subtilisin/kexin type 9, a protein that targets LDL receptors for degradation and thereby reduces the liver's ability to remove LDL-C from the blood. In Phase II and III trials in more than 6000 subjects with primary hypercholesterolemia, evolocumab reduced LDL-C by 50-75% compared with placebo and by 35-45% compared with ezetimibe. Evolocumab reduced the proatherogenic lipid profile, including Lp(a), and modestly increased HDL-C and ApoA1. In subjects with homozygous familial hypercholesterolemia, evolocumab reduced LDL-C by 30%. Safety and tolerability of evolocumab was similar to that of placebo and ezetimibe. The ongoing FOURIER trial, anticipated to report in 2017, will provide definitive evidence on cardiovascular endpoints and additional long-term safety.