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 Jr. Jack, Kejal M Kantarci, Pamela F. Schwartz, William T. Duggan, Qinying Zhao, Ken Sprenger, Martin M. Bednar, Brendon Binneman

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 1 2017

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Alzheimer Disease
Safety
Placebos
Cerebrospinal Fluid
ponezumab
Amyloid
Headache
Anti-Idiotypic Antibodies
Biomarkers
Brain

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

Cite this

Multiple-dose ponezumab for mild-to-moderate Alzheimer's disease : Safety and efficacy. / Landen, Jaren W.; Cohen, Sharon; Billing, Clare B.; Cronenberger, Carol; Styren, Scot; Burstein, Aaron H.; Sattler, Catherine; Lee, Jae Hong; Jack, Clifford R Jr.; Kantarci, Kejal M; Schwartz, Pamela F.; Duggan, William T.; Zhao, Qinying; Sprenger, Ken; Bednar, Martin M.; Binneman, Brendon.

In: Alzheimer's and Dementia: Translational Research and Clinical Interventions, Vol. 3, No. 3, 01.09.2017, p. 339-347.

Research output: Contribution to journalArticle

Landen, JW, Cohen, S, Billing, CB, Cronenberger, C, Styren, S, Burstein, AH, Sattler, C, Lee, JH, Jack, CRJ, Kantarci, KM, Schwartz, PF, Duggan, WT, Zhao, Q, Sprenger, K, Bednar, MM & 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, vol. 3, no. 3, pp. 339-347. https://doi.org/10.1016/j.trci.2017.04.003
Landen, Jaren W. ; Cohen, Sharon ; Billing, Clare B. ; Cronenberger, Carol ; Styren, Scot ; Burstein, Aaron H. ; Sattler, Catherine ; Lee, Jae Hong ; Jack, Clifford R Jr. ; Kantarci, Kejal M ; Schwartz, Pamela F. ; Duggan, William T. ; Zhao, Qinying ; Sprenger, Ken ; Bednar, Martin M. ; Binneman, Brendon. / Multiple-dose ponezumab for mild-to-moderate Alzheimer's disease : Safety and efficacy. In: Alzheimer's and Dementia: Translational Research and Clinical Interventions. 2017 ; Vol. 3, No. 3. pp. 339-347.
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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.",
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T1 - Multiple-dose ponezumab for mild-to-moderate Alzheimer's disease

T2 - Safety and efficacy

AU - Landen, Jaren W.

AU - Cohen, Sharon

AU - Billing, Clare B.

AU - Cronenberger, Carol

AU - Styren, Scot

AU - Burstein, Aaron H.

AU - Sattler, Catherine

AU - Lee, Jae Hong

AU - Jack, Clifford R Jr.

AU - Kantarci, Kejal M

AU - Schwartz, Pamela F.

AU - Duggan, William T.

AU - Zhao, Qinying

AU - Sprenger, Ken

AU - Bednar, Martin M.

AU - Binneman, Brendon

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N2 - 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.

AB - 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.

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KW - Cerebrospinal fluid

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KW - Phase-II study

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