title: Long-term safety and tolerability of bapineuzumab in patients with Alzheimer's disease in two phase 3 extension studies.
abstract: BACKGROUND
  Immunotherapy with monoclonal antibodies that target amyloid beta has been under investigation as a treatment for patients with Alzheimer's disease (AD). The 3000 and 3001 phase 3 clinical studies of intravenous bapineuzumab assessed safety and efficacy in patients with mild to moderate AD recruited in over 26 countries. This article describes the long-term safety and tolerability of bapineuzumab in the extension studies for these two protocols.
  
  
  METHODS
  The long-term safety and tolerability of intravenous-administered bapineuzumab in patients with AD was evaluated in apolipoprotein E ε4 allele noncarriers (Study 3002, extension of Study 3000) and apolipoprotein E ε4 allele carriers (Study 3003, extension of Study 3001). Those receiving bapineuzumab in the parent study were continued at the same dose; if receiving placebo, patients began bapineuzumab. Bapineuzumab doses were 0.5 mg/kg in both studies and also 1.0 mg/kg in the noncarrier study. Clinical efficacy of bapineuzumab was also assessed in exploratory analyses.
  
  
  RESULTS
  Because of lack of efficacy in two other phase 3 trials, the parent protocols were stopped early. As a result, Studies 3002 and 3003 were also terminated. In total, 492 and 202 patients were enrolled in Studies 3003 and 3002, respectively. In apolipoprotein E ε4 carriers (Study 3003), treatment-emergent adverse events occurred in 70.7% of the patients who originally received placebo and 66.9% of those who originally received bapineuzumab. In noncarriers, treatment-emergent adverse events occurred in 82.1% and 67.6% of patients who received placebo + bapineuzumab 0.5 mg/kg and placebo + bapineuzumab 1.0 mg/kg, respectively, and in 72.7% and 64.3% of those who received bapineuzumab + bapineuzumab 0.5 mg/kg and 1.0 mg/kg, respectively. Amyloid-related imaging abnormalities with edema or effusions were the main bapineuzumab-associated adverse events in both studies, occurring in approximately 11% of placebo + bapineuzumab and 4% of bapineuzumab + bapineuzumab groups overall. Exploratory analyses of clinical efficacy were not significantly different between groups in either study.
  
  
  CONCLUSIONS
  In these phase 3 extension studies, intravenous bapineuzumab administered for up to approximately 3 years showed no unexpected safety signals and a safety profile consistent with previous bapineuzumab trials.
  
  
  BACKGROUND
  Noncarriers (Study 3002): ClinicalTrials.gov NCT00996918 . Registered 14 October 2009. Carriers (Study 3003): ClinicalTrials.gov NCT00998764 . Registered 16 October 2009.
authors.affiliation: Université Catholique de Louvain, Cliniques Universitaires Saint-Luc, 10 Avenue Hipocrate, B-1200, Bruxelles, Belgium. adrian.ivanoiu@uclouvain.be.
authors.forename: Adrian
authors.initials: A
authors.lastname: Ivanoiu
authors.affiliation: Centre d'investigation Clinique, Centre Mémoire et Langage, Service de Neurologie, CHU Purpan, Place du Dr Baylac, 31059, Toulouse, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Pariente
authors.affiliation: Pfizer Inc., 500 Arcola Road, Collegeville, PA, 19426, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Booth
authors.affiliation: Pfizer Inc., 500 Arcola Road, Collegeville, PA, 19426, USA.
authors.forename: Kasia
authors.initials: K
authors.lastname: Lobello
authors.affiliation: Pfizer PGRD, 23-25 avenue du Docteur Lannelongue, 75668, Paris cedex 14, France.
authors.forename: Gerald
authors.initials: G
authors.lastname: Luscan
authors.affiliation: Pfizer Inc., 500 Arcola Road, Collegeville, PA, 19426, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Hua
authors.affiliation: Pfizer PGRD, 23-25 avenue du Docteur Lannelongue, 75668, Paris cedex 14, France.
authors.forename: Prisca
authors.initials: P
authors.lastname: Lucas
authors.affiliation: Pfizer Inc., Eastern Point Road, Groton, CT, 06340, USA.
authors.forename: Scot
authors.initials: S
authors.lastname: Styren
authors.affiliation: Pfizer Inc., 500 Arcola Road, Collegeville, PA, 19426, USA.
authors.forename: Lingfeng
authors.initials: L
authors.lastname: Yang
authors.affiliation: Pfizer Inc., 500 Arcola Road, Collegeville, PA, 19426, USA.
authors.forename: David
authors.initials: D
authors.lastname: Li
authors.affiliation: Pfizer Inc., 500 Arcola Road, Collegeville, PA, 19426, USA.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Black
authors.affiliation: Janssen Alzheimer Immunotherapy Research & Development, LLC, 700 Gateway Blvd., South San Francisco, CA, 94080, USA.
authors.forename: H Robert
authors.initials: HR
authors.lastname: Brashear
authors.affiliation: Pfizer Inc., 235 East 42nd Street, New York, NY, 10017, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: McRae
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000235:genetics / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D001057:Apolipoproteins E; C545458:bapineuzumab
keywords: Alzheimer’s disease; Amyloid beta; Amyloid-related imaging abnormalities with edema or effusions/vasogenic edema; Bapineuzumab; Immunotherapy