title: Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 monoclonal antibody alirocumab vs placebo in patients with heterozygous familial hypercholesterolemia.
abstract: Patients with heterozygous familial hypercholesterolemia (HeFH) are characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels. Long-term effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition have not been thoroughly investigated in these patients.
  
  
  
  We evaluated efficacy and safety of alirocumab, a PCSK9 inhibitor, vs placebo in patients with HeFH.
  
  
  
  In total, 1257 patients with HeFH on maximally tolerated statin ± other lipid-lowering therapies from four 78-week ODYSSEY trials were analyzed. In FH I and II, patients with baseline LDL-C levels ≥70/100 mg/dL (n = 735), depending on documented cardiovascular disease history, received placebo or alirocumab 75 mg every 2 weeks (Q2W; with dose increase to 150 mg Q2W at week 12 if week 8 LDL-C was ≥70 mg/dL). Separately, data were pooled from HIGH FH (baseline LDL-C ≥160 mg/dL) and patients with HeFH from LONG TERM (baseline LDL-C ≥70 mg/dL), where patients received placebo or alirocumab 150 mg Q2W (n = 522).
  
  
  
  At week 24, alirocumab reduced LDL-C levels by -48.8% (75/150 mg Q2W; placebo: +7.1%) and -55.0% (alirocumab 150 mg Q2W; placebo: +1.3%) (both P < .0001 vs placebo; intention-to-treat analysis). Least-squares mean LDL-C levels of 69.1 to 75.6 mg/dL (alirocumab 75/150 mg/dL Q2W; baseline: 141.3 mg/dL) and 72.2 to 82.3 mg/dL (alirocumab 150 mg Q2W; baseline: 168.4 mg/dL) were achieved at weeks 24 to 78 (on-treatment analysis). Additional beneficial effects were observed in other lipids. Treatment-emergent adverse event rates were similar in the alirocumab (80.5%) and placebo groups (83.0%).
  
  
  
  In this large cohort of patients with HeFH, alirocumab significantly reduced LDL-C levels. Alirocumab was generally well tolerated.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: j.j.kastelein@amc.uva.nl.
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.affiliation: Lipid Clinic, Oslo University Hospital, Oslo, Norway.
authors.forename: Gisle
authors.initials: G
authors.lastname: Langslet
authors.affiliation: Sanofi, Montpellier, France.
authors.forename: Marie T
authors.initials: MT
authors.lastname: Baccara-Dinet
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Gipe
authors.affiliation: Sanofi, Bridgewater, NJ, USA.
authors.forename: Umesh
authors.initials: U
authors.lastname: Chaudhari
authors.affiliation: Regeneron Pharmaceuticals, Inc., Basking Ridge, NJ, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Sanofi, Chilly-Mazarin, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Minini
authors.affiliation: Lipid Clinic, Point Médical, Dijon, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Farnier
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9 / Q000276:immunology*; D012449:Safety
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; C571059:alirocumab
keywords: Alirocumab; Cholesterol; Double-blind; HeFH; LDL-C; Lipid lowering; Lipid therapy; Maximally tolerated statin; PCSK9; Placebo-controlled