Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 54, Issue 4, Pages 1509-1519Publisher
IOS PRESS
DOI: 10.3233/JAD-160369
Keywords
Alzheimer's disease; amyloid burden; bapineuzumab; biomarker; pharmacokinetics
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Funding
- Janssen Alzheimer Immunotherapy Research & Development, LLC
- Pfizer Inc
- Janssen Research & Development, LLC
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Background: Bapineuzumab, a humanized monoclonal antibody, targets amyloid-beta (A beta(1-40/1-42)) that is believed to play a key role in the pathogenesis of Alzheimer disease (AD). Objectives: To assess the effects of monthly subcutaneous (SC) bapineuzumab versus placebo on cerebral amyloid signal in amyloid-positive patients with mild to moderate AD. The incidence of amyloid-related imaging abnormalities-edema/effusion (ARIA-E), pharmacokinetics, pharmacodynamics, immunogenicity, and other safety aspects of bapineuzumab were also evaluated. Methods: In this multicenter, double-blind study, 146 patients were randomized (1 : 1: 1 : 1) to SC bapineuzumab 2, 7, or 20 mg/month or placebo. Lack of efficacy of intravenous (IV) bapineuzumab in Phase III studies led to truncation of the treatment duration from 24 months to 12 months. Primary endpoint: change from baseline to month 12 in brain amyloid signal as measured by standardized uptake value ratio (SUVR) using florbetapir positron emission tomography (PET). Results: Florbetapir PET SUVR decreased significantly (p = 0.038) from baseline to month 12 for the bapineuzumab 7 mg/month group only; reductions versus placebo were not significant for any dosage. One patient each in bapineuzumab 2 mg/month and 20 mg/month groups had ARIA-E. The percentages of patients with treatment-emergent adverse events were similar in placebo (77.8%) and bapineuzumab 2 mg/month (78.4%) group, but higher in 7 mg/month (94.4%) and 20 mg/month (89.2%) groups. Conclusion: Bapineuzumab SC once-monthly did not demonstrate significant treatment difference over placebo on cerebral amyloid signal at one year but was well-tolerated. There was less ARIA-E than had been expected based on prior experience with comparable exposure on IV bapineuzumab.
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