title: A phase III randomized trial evaluating alirocumab 300 mg every 4 weeks as monotherapy or add-on to statin: ODYSSEY CHOICE I.
abstract: In previous phase III studies, the PCSK9 monoclonal antibody alirocumab was administered at doses of 75 or 150 mg every 2 weeks (Q2W). CHOICE I (NCT01926782) evaluated 300 mg every 4 weeks (Q4W) in patients on either maximally tolerated statin or no statin, both ± other lipid-lowering therapies.
  
  
  
  CHOICE I included patients with hypercholesterolemia at moderate-to-very-high cardiovascular risk. Patients were randomized to alirocumab 300 mg Q4W, 75 mg Q2W (calibrator arm), or placebo for 48 weeks, with dose adjustment for either alirocumab arm to 150 mg Q2W at Week (W) 12 if at W8 LDL-C levels were >70/100 mg/dL (1.8/2.6 mmol/L) depending on cardiovascular risk or LDL-C reduction was <30% from baseline. Co-primary endpoints were percent LDL-C change from baseline to W24, and to time-averaged LDL-C over W21-24.
  
  
  
  Approximately two-thirds of randomized patients were receiving statins. At W12, 14.7% (no statin) and 19.3% (statin) of patients receiving alirocumab 300 mg Q4W required dose adjustment. At W24, significant LDL-C reductions from baseline were observed with alirocumab 300 mg Q4W: mean differences were -52.7% (no statin; placebo: -0.3%) and -58.8% (statin; placebo: -0.1%). Average LDL-C reductions from baseline to W21-24 were also significantly greater with alirocumab 300 mg Q4W vs. placebo in patients not receiving (-56.9% vs. -1.6%) and receiving statin (-65.8% vs. -0.8%). Treatment-emergent adverse event rates ranged from 61.1 to 75.0% (placebo) and 71.5 to 78.1% (alirocumab 300 mg Q4W).
  
  
  
  Alirocumab 300 mg Q4W is a viable additional treatment option in patients requiring LDL-C-lowering.
authors.affiliation: The Sterling Research Group, 2230 Auburn Avenue, Cincinnati, OH 45219, USA. Electronic address: eroth@sterlingresearch.org.
authors.forename: Eli M
authors.initials: EM
authors.lastname: Roth
authors.affiliation: Department of Internal Medicine, Division of Clinical Pharmacology, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Moriarty
authors.affiliation: Clinique des Maladies Lipidiques, Department of Medicine, Centre Hospitalier Universitaire de Québec - Université Laval Québec, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Bergeron
authors.affiliation: Lipid Clinic, Oslo University Hospital, Oslo, Norway.
authors.forename: Gisle
authors.initials: G
authors.lastname: Langslet
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
authors.forename: Garen
authors.initials: G
authors.lastname: Manvelian
authors.affiliation: Regeneron Pharmaceuticals, Inc., Basking Ridge, NJ, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Sanofi, Montpellier, France.
authors.forename: Marie T
authors.initials: MT
authors.lastname: Baccara-Dinet
authors.affiliation: Department of Medicine, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000069059:Atorvastatin / Q000008:administration & dosage; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9 / Q000378:metabolism; D019821:Simvastatin / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069059:Atorvastatin; D019821:Simvastatin; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; C571059:alirocumab
keywords: Alirocumab; Cardiovascular risk; LDL-C; PCSK9; Phase III; Placebo-controlled; Randomized