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Ponezumab in mild-to-moderate Alzheimer's disease : Randomized phase II PET-PIB study

Landen, Jaren W.; Andreasen, Niels; Cronenberger, Carol L.; Schwartz, Pamela F.; Börjesson-Hanson, Anne; Östlund, Henrik LU ; Sattler, Catherine A.; Binneman, Brendon and Bednar, Martin M. (2017) In Alzheimer's and Dementia: Translational Research and Clinical Interventions 3(3). p.393-401
Abstract

Introduction The safety, pharmacokinetics, and effect on peripheral and central amyloid β (Aβ) of multiple doses of ponezumab, an anti-Aβ monoclonal antibody, were characterized in subjects with mild-to-moderate Alzheimer's disease treated for 1 year. Methods Subjects were aged ≥50 years with Mini–Mental State Examination scores 16 to 26. Cohort Q was randomized to ponezumab 10 mg/kg (n = 12) or placebo (n = 6) quarterly. Cohort M was randomized to a loading dose of ponezumab 10 mg/kg or placebo, followed by monthly ponezumab 7.5 mg/kg (n = 12) or placebo (n = 6), respectively. Results Ponezumab was generally well tolerated. Plasma concentrations increased dose dependently, but cerebrospinal fluid (CSF) penetration was low. Plasma Aβ... (More)

Introduction The safety, pharmacokinetics, and effect on peripheral and central amyloid β (Aβ) of multiple doses of ponezumab, an anti-Aβ monoclonal antibody, were characterized in subjects with mild-to-moderate Alzheimer's disease treated for 1 year. Methods Subjects were aged ≥50 years with Mini–Mental State Examination scores 16 to 26. Cohort Q was randomized to ponezumab 10 mg/kg (n = 12) or placebo (n = 6) quarterly. Cohort M was randomized to a loading dose of ponezumab 10 mg/kg or placebo, followed by monthly ponezumab 7.5 mg/kg (n = 12) or placebo (n = 6), respectively. Results Ponezumab was generally well tolerated. Plasma concentrations increased dose dependently, but cerebrospinal fluid (CSF) penetration was low. Plasma Aβ increased dose dependently with ponezumab, but CSF biomarkers, brain amyloid burden, cognition, and function were not affected. Conclusions Both ponezumab dosing schedules were generally safe and well tolerated but did not alter CSF biomarkers, brain amyloid burden, or clinical outcomes.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, Amyloid, Anti-drug antibodies, Antibody, Pharmacodynamics, Pharmacokinetics, PIB, Ponezumab, Safety, Tolerability
in
Alzheimer's and Dementia: Translational Research and Clinical Interventions
volume
3
issue
3
pages
9 pages
publisher
Elsevier Inc.
external identifiers
  • scopus:85022009680
DOI
10.1016/j.trci.2017.05.003
language
English
LU publication?
yes
id
9e7fa0b5-9011-4c6e-90bb-6f648eebfb46
date added to LUP
2017-07-31 10:30:44
date last changed
2017-07-31 10:30:44
@article{9e7fa0b5-9011-4c6e-90bb-6f648eebfb46,
  abstract     = {<p>Introduction The safety, pharmacokinetics, and effect on peripheral and central amyloid β (Aβ) of multiple doses of ponezumab, an anti-Aβ monoclonal antibody, were characterized in subjects with mild-to-moderate Alzheimer's disease treated for 1 year. Methods Subjects were aged ≥50 years with Mini–Mental State Examination scores 16 to 26. Cohort Q was randomized to ponezumab 10 mg/kg (n = 12) or placebo (n = 6) quarterly. Cohort M was randomized to a loading dose of ponezumab 10 mg/kg or placebo, followed by monthly ponezumab 7.5 mg/kg (n = 12) or placebo (n = 6), respectively. Results Ponezumab was generally well tolerated. Plasma concentrations increased dose dependently, but cerebrospinal fluid (CSF) penetration was low. Plasma Aβ increased dose dependently with ponezumab, but CSF biomarkers, brain amyloid burden, cognition, and function were not affected. Conclusions Both ponezumab dosing schedules were generally safe and well tolerated but did not alter CSF biomarkers, brain amyloid burden, or clinical outcomes.</p>},
  author       = {Landen, Jaren W. and Andreasen, Niels and Cronenberger, Carol L. and Schwartz, Pamela F. and Börjesson-Hanson, Anne and Östlund, Henrik and Sattler, Catherine A. and Binneman, Brendon and Bednar, Martin M.},
  keyword      = {Alzheimer's disease,Amyloid,Anti-drug antibodies,Antibody,Pharmacodynamics,Pharmacokinetics,PIB,Ponezumab,Safety,Tolerability},
  language     = {eng},
  month        = {09},
  number       = {3},
  pages        = {393--401},
  publisher    = {Elsevier Inc.},
  series       = {Alzheimer's and Dementia: Translational Research and Clinical Interventions},
  title        = {Ponezumab in mild-to-moderate Alzheimer's disease : Randomized phase II PET-PIB study},
  url          = {http://dx.doi.org/10.1016/j.trci.2017.05.003},
  volume       = {3},
  year         = {2017},
}