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

Alzheimer's and Dementia: Translational Research and Clinical Interventions - Tập 3 - Trang 339-347 - 2017
Jaren W. Landen1, Sharon Cohen2, Clare B. Billing1, Carol Cronenberger1, Scot Styren1, Aaron H. Burstein1, Catherine Sattler1, Jae-Hong Lee3, Clifford R. Jack4, Kejal Kantarci4, Pamela F. Schwartz1, William T. Duggan1, Qinying Zhao1, Ken Sprenger1, Martin M. Bednar5, Brendon Binneman5
1Pfizer, Inc., Groton, CT, USA
2Toronto Memory Program, Toronto, Ontario, Canada
3Department of Neurology, Asan Medical Center, Seoul, Korea
4Department of Radiology, Mayo Clinic, Rochester, MN, USA
5Pfizer Inc, Cambridge, MA, USA

Tóm tắt

AbstractIntroductionMultiple intravenous doses of ponezumab, an anti‐amyloid antibody, were evaluated in subjects with mild‐to‐moderate Alzheimer's disease (AD).MethodsIn 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.ResultsPonezumab 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.ConclusionsMultiple‐dose ponezumab was generally safe, but not efficacious, in mild‐to‐moderate AD.

Tài liệu tham khảo

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Alzheimer's and Dementia: Translational Research and Clinical Interventions

Tập 3

339-347

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