title: Effect of Alirocumab on Lipoprotein(a) Over ≥1.5 Years (from the Phase 3 ODYSSEY Program).
abstract: Elevated lipoprotein(a) [Lp(a)] is independently associated with increased cardiovascular risk. However, treatment options for elevated Lp(a) are limited. Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, reduced low-density lipoprotein cholesterol (LDL-C) by up to 62% from baseline in phase 3 studies, with adverse event rates similar between alirocumab and controls. We evaluated the effect of alirocumab on serum Lp(a) using pooled data from the phase 3 ODYSSEY program: 4,915 patients with hypercholesterolemia from 10 phase 3 studies were included. Eight studies evaluated alirocumab 75 mg every 2 weeks (Q2W), with possible increase to 150 mg Q2W at week 12 depending on LDL-C at week 8 (75/150 mg Q2W); the other 2 studies evaluated alirocumab 150-mg Q2W from the outset. Comparators were placebo or ezetimibe. Eight studies were conducted on a background of statins, and 2 studies were carried out with no statins. Alirocumab was associated with significant reductions in Lp(a), regardless of starting dose and use of concomitant statins. At week 24, reductions from baseline were 23% to 27% with alirocumab 75/150-mg Q2W and 29% with alirocumab 150-mg Q2W (all comparisons p <0.0001 vs controls). Reductions were sustained over 78 to 104 weeks. Lp(a) reductions with alirocumab were independent of race, gender, presence of familial hypercholesterolemia, baseline Lp(a), and LDL-C concentrations, or use of statins. In conclusion, in addition to marked reduction in LDL-C, alirocumab leads to a significant and sustained lowering of Lp(a).
authors: Department of Medicine, ECOGENE-21 Clinical and Translational Research Center and Lipidology Unit, Université de Montréal, Chicoutimi, Quebec, Canada. Electronic address: daniel.gaudet@umontreal.ca.
authors: Daniel
authors: D
authors: Gaudet
authors: Lipid Disorders Clinic, Centre for Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
authors: Gerald F
authors: GF
authors: Watts
authors: University of Iowa, Iowa City, Iowa.
authors: Jennifer G
authors: JG
authors: Robinson
authors: Biostatistics and Programming, Sanofi, Chilly-Mazarin, France.
authors: Pascal
authors: P
authors: Minini
authors: Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
authors: William J
authors: WJ
authors: Sasiela
authors: Sanofi, Bridgewater, New Jersey.
authors: Jay
authors: J
authors: Edelberg
authors: Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
authors: Michael J
authors: MJ
authors: Louie
authors: Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.
authors: Frederick J
authors: FJ
authors: Raal
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy*; D017270:Lipoprotein(a) / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017270:Lipoprotein(a); D000069438:Ezetimibe; C571059:alirocumab