title: Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial.
abstract: To evaluate the effect of alirocumab on frequency of standard apheresis treatments [weekly or every 2 weeks (Q2W)] in heterozygous familial hypercholesterolaemia (HeFH).
  
  
  
  ODYSSEY ESCAPE (NCT02326220) was a double-blind study in 62 HeFH patients undergoing regular weekly or Q2W lipoprotein apheresis. Patients were randomly assigned (2:1, respectively) to receive alirocumab 150 mg (n = 41) or placebo (n = 21) Q2W subcutaneously for 18 weeks. From day 1 to week 6, apheresis rate was fixed according to the patient's established schedule; from weeks 7 to 18, apheresis rate was adjusted based on the patient's low-density lipoprotein cholesterol (LDL-C) response in a blinded fashion. Apheresis was not performed when the LDL-C value was ≥30% lower than the baseline (pre-apheresis) value. The primary efficacy endpoint was the rate of apheresis treatments over 12 weeks (weeks 7-18), standardized to number of planned treatments. In the alirocumab group the least square (LS) mean ± SE (95% confidence interval [CI]) per cent change in pre-apheresis LDL-C from baseline at week 6 was -53.7 ± 2.3 (-58.2 to - 49.2) compared with 1.6 ± 3.1 (-4.7 to 7.9) in the placebo group. The primary efficacy endpoint showed statistically significant benefit in favour of alirocumab (Hodges-Lehmann median estimate of treatment difference: 0.75; 95% CI 0.67-0.83; P < 0.0001). Therefore, alirocumab-treated patients had a 0.75 (75%) additional reduction in the standardized rate of apheresis treatments vs. placebo-treated patients. During this period, 63.4% of patients on alirocumab avoided all and 92.7% avoided at least half of the apheresis treatments. Adverse event rates were similar (75.6% of patients on alirocumab vs. 76.2% on placebo).
  
  
  
  Lipoprotein apheresis was discontinued in 63.4% of patients on alirocumab who were previously undergoing regular apheresis, and the rate was at least halved in 92.7% of patients. Alirocumab was generally safe and well tolerated.
authors: Division of Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA pmoriart@kumc.edu.
authors: Patrick M
authors: PM
authors: Moriarty
authors: Medical Department II, Grosshadern, University Munich, Marchioninistraße 15, 81377 Munich, Germany.
authors: Klaus G
authors: KG
authors: Parhofer
authors: Metabolic Leader, LLC, 71 US Route 1 Suite J, Scarborough, ME 04074-9375, USA.
authors: Stephan P
authors: SP
authors: Babirak
authors: Division of Endocrinology, Metabolism and Diabetes, Anschutz Health and Wellness Center-Anschutz Medical Campus, Aurora, CO 80045, USA.
authors: Marc-Andre
authors: MA
authors: Cornier
authors: Knight Cardiovascular Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, L607, Portland, OR 97239, USA.
authors: P Barton
authors: PB
authors: Duell
authors: Department of Internal Medicine III, Extracorporeal Treatment and Lipoprotein Apheresis Center, University Hospital Carl Gustav Carus, Technische Universitaet Dresden, 01069 Dresden, Germany.
authors: Bernd
authors: B
authors: Hohenstein
authors: Apherese Zentrum Passau, Innstrasse 76, 94032 Passau, Germany.
authors: Josef
authors: J
authors: Leebmann
authors: Apheresis Centrum Rostock, Nobelstr. 53, 18059 Rostock, Germany.
authors: Wolfgang
authors: W
authors: Ramlow
authors: Apheresis Centre, Nehrologisches Zentrum Göttingen GbR, An der Lutter 24, D-37075 Göttingen, Germany.
authors: Volker
authors: V
authors: Schettler
authors: Mayo Clinic, Rochester, 200 First Street SW, Rochester, MN 55905, USA.
authors: Vinaya
authors: V
authors: Simha
authors: Charite-Universitätsmedizin Berlin-Campus Virchow-Klinikum, Augustenburger Platz 1, Ostring 3, Berlin 13353, Germany.
authors: Elisabeth
authors: E
authors: Steinhagen-Thiessen
authors: Cardiology, Hartford Hospital, 80 Seymour Street, JB722, Hartford, CT 06102, USA.
authors: Paul D
authors: PD
authors: Thompson
authors: Medizinische Klinik und Poliklinik IV, LMU Klinikum der Universität München, 81377 Munich, Germany.
authors: Anja
authors: A
authors: Vogt
authors: Medical Department, Sanofi-Aventis Deutschland GmbH, Potsdamer Straße 8, 10785 Berlin, Germany.
authors: Berndt
authors: B
authors: von Stritzky
authors: Regeneron Pharmaceuticals, Inc., 110 Allen Road, Basking Ridge, NJ 07920, USA.
authors: Yunling
authors: Y
authors: Du
authors: Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.
authors: Garen
authors: G
authors: Manvelian
mesh_terms: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D001781:Blood Component Removal; D008078:Cholesterol, LDL; D004311:Double-Blind Method; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006938:Hyperlipoproteinemia Type II; D008074:Lipoproteins; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins; C571059:alirocumab
keywords: Alirocumab; Familial hypercholesterolaemia; Low-density lipoprotein cholesterol; Low-density lipoprotein receptor; Monoclonal antibody; Proprotein convertase subtilisin/kexin type 9