BACKGROUND: Bapineuzumab, a humanized anti-amyloid-beta (Abeta) monoclonal 
antibody for the potential treatment of Alzheimer disease (AD), was evaluated in 
a multiple ascending dose, safety, and efficacy study in mild to moderate AD.
METHODS: The study enrolled 234 patients, randomly assigned to IV bapineuzumab 
or placebo in 4 dose cohorts (0.15, 0.5, 1.0, or 2.0 mg/kg). Patients received 6 
infusions, 13 weeks apart, with final assessments at week 78. The prespecified 
primary efficacy analysis in the modified intent-to-treat population assumed 
linear decline and compared treatment differences within dose cohorts on the 
Alzheimer's Disease Assessment Scale-Cognitive and Disability Assessment for 
Dementia. Exploratory analyses combined dose cohorts and did not assume a 
specific pattern of decline.
RESULTS: No significant differences were found in the primary efficacy analysis. 
Exploratory analyses showed potential treatment differences (p < 0.05, 
unadjusted for multiple comparisons) on cognitive and functional endpoints in 
study "completers" and APOE epsilon4 noncarriers. Reversible vasogenic edema, 
detected on brain MRI in 12/124 (9.7%) bapineuzumab-treated patients, was more 
frequent in higher dose groups and APOE epsilon4 carriers. Six vasogenic edema 
patients were asymptomatic; 6 experienced transient symptoms.
CONCLUSIONS: Primary efficacy outcomes in this phase 2 trial were not 
significant. Potential treatment differences in the exploratory analyses support 
further investigation of bapineuzumab in phase 3 with special attention to APOE 
epsilon4 carrier status.
CLASSIFICATION OF EVIDENCE: Due to varying doses and a lack of statistical 
precision, this Class II ascending dose trial provides insufficient evidence to 
support or refute a benefit of bapineuzumab.