Multiple-dose ponezumab for mild-to-moderate Alzheimer's disease: Safety and efficacy

Jaren W. Landen, Sharon Cohen, Clare B. Billing, Carol Cronenberger, Scot Styren, Aaron H. Burstein, Catherine Sattler, Jae Hong Lee, Clifford R. Jack, Kejal Kantarci, Pamela F. Schwartz, William T. Duggan, Qinying Zhao, Ken Sprenger, Martin M. Bednar, Brendon Binneman

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Introduction Multiple intravenous doses of ponezumab, an anti-amyloid antibody, were evaluated in subjects with mild-to-moderate Alzheimer's disease (AD). Methods In part A, 77 subjects were randomized to ponezumab 0.1, 0.5, or 1 mg/kg (75 treated) and 26 to placebo (24 treated). In part B, 63 subjects were randomized and treated with ponezumab 3 or 8.5 mg/kg and 32 with placebo. Subjects received 10 infusions over 18 months and were followed for 6 months thereafter. Results Ponezumab was generally safe and well tolerated. Most common adverse events were fall (16.7% ponezumab, 21.4% placebo), headache (13.8%, 21.4%), and cerebral microhemorrhage (13.8%, 19.6%). Plasma ponezumab increased dose-dependently with limited accumulation. Cerebrospinal fluid penetration was low. Plasma Aβ1–x and Aβ1–40 showed robust increases, but cerebrospinal fluid biomarkers showed no dose response. Ponezumab had no effects on cognitive/functional outcomes or brain volume. Conclusions Multiple-dose ponezumab was generally safe, but not efficacious, in mild-to-moderate AD.

Original languageEnglish (US)
Pages (from-to)339-347
Number of pages9
JournalAlzheimer's and Dementia: Translational Research and Clinical Interventions
Volume3
Issue number3
DOIs
StatePublished - Sep 2017

Keywords

  • Alzheimer's disease
  • Amyloid β
  • Biomarkers
  • Cerebrospinal fluid
  • Immunotherapy
  • Monoclonal antibody
  • Pharmacodynamics
  • Pharmacokinetics
  • Phase-II study
  • Ponezumab

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health

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  • Cite this

    Landen, J. W., Cohen, S., Billing, C. B., Cronenberger, C., Styren, S., Burstein, A. H., Sattler, C., Lee, J. H., Jack, C. R., Kantarci, K., Schwartz, P. F., Duggan, W. T., Zhao, Q., Sprenger, K., Bednar, M. M., & Binneman, B. (2017). Multiple-dose ponezumab for mild-to-moderate Alzheimer's disease: Safety and efficacy. Alzheimer's and Dementia: Translational Research and Clinical Interventions, 3(3), 339-347. https://doi.org/10.1016/j.trci.2017.04.003