title: Efficacy of alirocumab in high cardiovascular risk populations with or without heterozygous familial hypercholesterolemia: Pooled analysis of eight ODYSSEY Phase 3 clinical program trials.
abstract: OBJECTIVE
  Despite maximally tolerated statin therapy, many patients with high cardiovascular risk, with or without heterozygous familial hypercholesterolemia may require additional low-density lipoprotein cholesterol (LDL-C) reduction. We report pooled alirocumab (ALI) efficacy and safety data from eight Phase 3 trials in 4629 hypercholesterolemia patients, receiving background statin therapy.
  
  
  METHODS
  Studies were pooled by ALI dose and control: ALI 75/150mg every 2weeks (Q2W; dose increased to 150mg Q2W at Week 12 based on Week 8 LDL-C) versus ezetimibe (EZE; Pool 1) or placebo (PBO; Pool 2), and ALI 150mg Q2W versus PBO (Pool 3).
  
  
  RESULTS
  Mean baseline LDL-C was 109 vs. 105mg/dL (Pool 1), 129 vs. 130mg/dL (Pool 2) and 126 vs. 125mg/dL (Pool 3). ALI 75/150mg Q2W reduced LDL-C by 48.9% (vs. -19.3% EZE) and 48.6% (vs. +4.2% PBO) from baseline to Week 24, and ALI 150mg Q2W reduced LDL-C by 60.4% (vs. +0.5% PBO; all p<0.0001). LDL-C reductions were sustained to Week 104. Risk-based LDL-C goals (<70mg/dL or <100mg/dL) were achieved by 78.0%, 75.2%, and 79.0% (Pool 1-3) of ALI-treated patients (vs. 52.4%, 6.4%, and 8.4%, respectively, for controls) at Week 24. Consistent reductions were observed in apolipoprotein B, non-high-density lipoprotein cholesterol, and lipoprotein (a) (p<0.0001 vs. control). Common adverse events in ALI-treated patients were nasopharyngitis, injection-site reactions, upper respiratory tract infections, and influenza.
  
  
  CONCLUSIONS
  Alirocumab treatment significantly reduced LDL-C in high cardiovascular risk patients, enabling most to achieve risk-based LDL-C goals.
authors: Lipid Clinic, Point Médical, Dijon, France. Electronic address: michelfarnier@nerim.net.
authors: Michel
authors: M
authors: Farnier
authors: Lipidology Unit, Community Genomic Medicine Center, Department of Medicine, Université de Montréal and ECOGENE-21 Clinical and Translational Research Center, Chicoutimi, Quebec, Canada.
authors: Daniel
authors: D
authors: Gaudet
authors: Global Medical Affairs, Sanofi, Paris, France.
authors: Velichka
authors: V
authors: Valcheva
authors: Biostatistics and Programming, Sanofi, Chilly-Mazarin, France.
authors: Pascal
authors: P
authors: Minini
authors: Biostatistics and Data Management, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
authors: Kathryn
authors: K
authors: Miller
authors: Department of Endocrinology, l'Institut du Thorax, Nantes University Hospital, Nantes, France.
authors: Bertrand
authors: B
authors: Cariou
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D002784:Cholesterol / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005602:France / Q000453:epidemiology; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D015994:Incidence; D011792:Quebec / Q000453:epidemiology; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002784:Cholesterol; C571059:alirocumab
keywords: Alirocumab; Hypercholesterolemia; Low-density lipoprotein cholesterol