title: Evolocumab (AMG 145) for primary hypercholesterolemia.
abstract: 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.
authors.affiliation: Lipid Clinic, Oslo University Hospital, Forskningsveien 2 B, N-0424 Oslo, Norway.
authors.forename: Gisle
authors.initials: G
authors.lastname: Langslet
authors.forename: Maurice
authors.initials: M
authors.lastname: Emery
authors.forename: Scott M
authors.initials: SM
authors.lastname: Wasserman
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D000069438:Ezetimibe / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy; D008055:Lipids / Q000097:blood; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D008055:Lipids; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D000069438:Ezetimibe; C577155:evolocumab
keywords: LDL cholesterol; PCSK9; cardiovascular disease; evolocumab; hypercholesterolemia