A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Safety, Pharmacokinetics, and Biomarker Results of Subcutaneous Bapineuzumab in Patients with mild to moderate Alzheimer's disease

• Published in: Journal of Alzheimer's disease Vol. 54; no. 4; p. 1509
• Main Authors: Brody, Mark, Liu, Enchi, Di, Jianing, Lu, Ming, Margolin, Richard A, Werth, John L, Booth, Kevin, Shadman, Anna, Brashear, H Robert, Novak, Gerald
• Format: Journal Article
• Language: English
• Published: Netherlands 18.10.2016
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - blood; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - drug therapy; Amyloid beta-Peptides - blood; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - blood; Biomarkers - blood; Double-Blind Method; Female; Follow-Up Studies; Humans; Injections, Subcutaneous; Male; Middle Aged; Peptide Fragments - blood; Positron-Emission Tomography - trends; pharmacokinetics; bapineuzumab; Alzheimer’s disease; biomarker; amyloid burden
• ISSN: 1875-8908
• DOI: 10.3233/JAD-160369

Bapineuzumab, a humanized monoclonal antibody, targets amyloid-β (Aβ1-40/1 -42) that is believed to play a key role in the pathogenesis of Alzheimer disease (AD). 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. 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). 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. 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.