title: Alirocumab: PCSK9 inhibitor for LDL cholesterol reduction.
abstract: The proof of concept that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition affects cholesterol levels was first established after the demonstration that PCSK9 loss-of-function mutations result in a significant drop in circulating LDL cholesterol levels. Subsequent studies revealed that PCSK9 binds the epidermal growth factor precursor homology domain-A on the surface LDL Receptor (LDLR) and directs LDLR and PCSK9 for lysosomal degradation. Alirocumab (also known as SAR236553/REGN727) is a monoclonal antibody that binds circulating PCSK9 and blocks its interactions with surface LDLR. Alirocumab clinical trials with different doses on different administration schedules were shown to significantly reduce LDL cholesterol both as a mono-therapy and in combination with statins or ezetimibe. Although there is great potential for anti-PCSK9 therapies in the management of cholesterol metabolism, there is no clear evidence yet that blocking PCSK9 reduces cardiovascular disease outcome. This is being investigated in ongoing Phase III clinical trials with alirocumab.
authors.affiliation: Knight Cardiovascular Institute, Center for Preventive Cardiology, Oregon Health and Science University, Portland, OR, USA. tavori@ohsu.edu
authors.forename: Hagai
authors.initials: H
authors.lastname: Tavori
authors.forename: Michelle
authors.initials: M
authors.lastname: Melone
authors.forename: Shirya
authors.initials: S
authors.lastname: Rashid
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D006801:Humans; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors*; D011973:Receptors, LDL / Q000378:metabolism; D012697:Serine Endopeptidases
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D011973:Receptors, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C571059:alirocumab
keywords: PCSK9; familial hypercholesterolemia; low-density lipoprotein; low-density lipoprotein receptor; monoclonal antibodies