Ponezumab in mild‐to‐moderate Alzheimer's disease: Randomized phase II PET‐PIB study. Issue 3 (8th June 2017)

• Record Type: Journal Article
• Authors: Landen, Jaren W.; Andreasen, Niels; Cronenberger, Carol L.; Schwartz, Pamela F.; Börjesson‐Hanson, Anne; Östlund, Henrik; Sattler, Catherine A.; Binneman, Brendon; Bednar, Martin M.
• Is Part Of: Alzheimer's & dementia. Volume 3:Issue 3(2017)
• Page Start: 393
• Page End: 401
• Publication Date: 2017-06-08
• Subjects: Alzheimer's disease -- Antibody -- Amyloid -- Pharmacokinetics -- Pharmacodynamics -- Ponezumab -- PIB -- Safety -- Tolerability -- Anti‐drug antibodies; Dementia -- Periodicals; Dementia -- Treatment -- Periodicals; Alzheimer's disease -- Treatment -- Periodicals; Alzheimer's disease -- Periodicals; 616.831
• DOI: 10.1016/j.trci.2017.05.003
• Languages: English
• ISSNs: 2352-8737

Abstract

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 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.