title: Open-label therapy with alirocumab in patients with heterozygous familial hypercholesterolemia: Results from three years of treatment.
abstract: PCSK9 inhibition with alirocumab significantly reduced LDL-C levels in trials of up to 78weeks' duration in patients with heterozygous familial hypercholesterolemia (HeFH). We report results from 3years of an ongoing open-label treatment extension (NCT01576484) to a 12-week double-blind trial in HeFH patients (NCT01266876).
  
  
  
  Patients who completed the parent study and were receiving stable daily statin±ezetimibe could enter the open-label extension, where they received alirocumab 150mg every 2 weeks (Q2W) subcutaneously (n=58). The primary endpoint was safety (treatment-emergent adverse events, TEAEs). Efficacy endpoints included the percentage change in LDL-C from baseline at Week 24. Safety and efficacy data were available up to Weeks 156 and 148, respectively.
  
  
  
  Mean baseline LDL-C was 150.7mg/dL (3.9mmol/L), despite all patients being on a statin (76% on high-intensity statin; 72% also receiving ezetimibe). Over 156weeks, 54 (93.1%) patients experienced a TEAE, 12 (20.7%) experienced a serious TEAE, and two (3.4%) discontinued due to a TEAE. Injection site reactions occurred in 21 (36.2%) patients. Mean (SD) reduction in LDL-C from baseline to Week 24 was 65.4 (21.1)%, with reductions maintained through 148weeks (Week 148 reduction: 56.0 [23.8]%). Mean apolipoprotein B reduction was 50.9% and median lipoprotein (a) reduction was 22.5% at Week 24 (46.1% and 25.6% at Week 148, respectively).
  
  
  
  Open-label treatment for 3years with alirocumab 150mg Q2W, administered with background statin±ezetimibe, was generally well-tolerated and had a safety profile comparable with that seen in the overall alirocumab clinical trial program. Alirocumab provided significant, sustained LDL-C reductions.
authors.affiliation: Institut de recherches cliniques de Montréal and Université de Montréal, Montréal, QC, Canada. Electronic address: robert.dufour@ircm.qc.ca.
authors.forename: Robert
authors.initials: R
authors.lastname: Dufour
authors.affiliation: Clinique des Maladies Lipidiques, Centre Hospitalier Universitaire de Québec-Université Laval, Quebec, QC, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Bergeron
authors.affiliation: ECOGENE-21 Clinical and Translational Research Center and Lipidology Unit, Department of Medicine, Université de Montreal, Chicoutimi, QC, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.affiliation: Maine Research Associates, Auburn, ME, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Weiss
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: Regeneron Pharmaceuticals Inc., Basking Ridge, NJ, USA.
authors.forename: Zhizhi
authors.initials: Z
authors.lastname: Qing
authors.affiliation: Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.affiliation: Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Andisik
authors.affiliation: Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Torri
authors.affiliation: Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Pordy
authors.affiliation: Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Gipe
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000069438:Ezetimibe / Q000627:therapeutic use; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069438:Ezetimibe; C571059:alirocumab
keywords: Alirocumab; LDL-C; Monoclonal antibody; Open-label; PCSK9