BACKGROUND: Alzheimer's disease is characterized by amyloid-beta plaques, 
neurofibrillary tangles, gliosis, and neuronal loss. Solanezumab, a humanized 
monoclonal antibody, preferentially binds soluble forms of amyloid and in 
preclinical studies promoted its clearance from the brain.
METHODS: In two phase 3, double-blind trials (EXPEDITION 1 and EXPEDITION 2), we 
randomly assigned 1012 and 1040 patients, respectively, with mild-to-moderate 
Alzheimer's disease to receive placebo or solanezumab (administered 
intravenously at a dose of 400 mg) every 4 weeks for 18 months. The primary 
outcomes were the changes from baseline to week 80 in scores on the 11-item 
cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog11; 
range, 0 to 70, with higher scores indicating greater cognitive impairment) and 
the Alzheimer's Disease Cooperative Study-Activities of Daily Living scale 
(ADCS-ADL; range, 0 to 78, with lower scores indicating worse functioning). 
After analysis of data from EXPEDITION 1, the primary outcome for EXPEDITION 2 
was revised to the change in scores on the 14-item cognitive subscale of the 
Alzheimer's Disease Assessment Scale (ADAS-cog14; range, 0 to 90, with higher 
scores indicating greater impairment), in patients with mild Alzheimer's 
disease.
RESULTS: Neither study showed significant improvement in the primary outcomes. 
The modeled difference between groups (solanezumab group minus placebo group) in 
the change from baseline was -0.8 points for the ADAS-cog11 score (95% 
confidence interval [CI], -2.1 to 0.5; P=0.24) and -0.4 points for the ADCS-ADL 
score (95% CI, -2.3 to 1.4; P=0.64) in EXPEDITION 1 and -1.3 points (95% CI, 
-2.5 to 0.3; P=0.06) and 1.6 points (95% CI, -0.2 to 3.3; P=0.08), respectively, 
in EXPEDITION 2. Between-group differences in the changes in the ADAS-cog14 
score were -1.7 points in patients with mild Alzheimer's disease (95% CI, -3.5 
to 0.1; P=0.06) and -1.5 in patients with moderate Alzheimer's disease (95% CI, 
-4.1 to 1.1; P=0.26). In the combined safety data set, the incidence of 
amyloid-related imaging abnormalities with edema or hemorrhage was 0.9% with 
solanezumab and 0.4% with placebo for edema (P=0.27) and 4.9% and 5.6%, 
respectively, for hemorrhage (P=0.49).
CONCLUSIONS: Solanezumab, a humanized monoclonal antibody that binds amyloid, 
failed to improve cognition or functional ability. (Funded by Eli Lilly; 
EXPEDITION 1 and 2 ClinicalTrials.gov numbers, NCT00905372 and NCT00904683.).