BACKGROUND: A hallmark of Alzheimer's disease is the accumulation of amyloid-β 
(Aβ) peptide. Donanemab, an antibody that targets a modified form of deposited 
Aβ, is being investigated for the treatment of early Alzheimer's disease.
METHODS: We conducted a phase 2 trial of donanemab in patients with early 
symptomatic Alzheimer's disease who had tau and amyloid deposition on 
positron-emission tomography (PET). Patients were randomly assigned in a 1:1 
ratio to receive donanemab (700 mg for the first three doses and 1400 mg 
thereafter) or placebo intravenously every 4 weeks for up to 72 weeks. The 
primary outcome was the change from baseline in the score on the Integrated 
Alzheimer's Disease Rating Scale (iADRS; range, 0 to 144, with lower scores 
indicating greater cognitive and functional impairment) at 76 weeks. Secondary 
outcomes included the change in scores on the Clinical Dementia Rating Scale-Sum 
of Boxes (CDR-SB), the 13-item cognitive subscale of the Alzheimer's Disease 
Assessment Scale (ADAS-Cog13), the Alzheimer's Disease Cooperative 
Study-Instrumental Activities of Daily Living Inventory (ADCS-iADL), and the 
Mini-Mental State Examination (MMSE), as well as the change in the amyloid and 
tau burden on PET.
RESULTS: A total of 257 patients were enrolled; 131 were assigned to receive 
donanemab and 126 to receive placebo. The baseline iADRS score was 106 in both 
groups. The change from baseline in the iADRS score at 76 weeks was -6.86 with 
donanemab and -10.06 with placebo (difference, 3.20; 95% confidence interval, 
0.12 to 6.27; P = 0.04). The results for most secondary outcomes showed no 
substantial difference. At 76 weeks, the reductions in the amyloid plaque level 
and the global tau load were 85.06 centiloids and 0.01 greater, respectively, 
with donanemab than with placebo. Amyloid-related cerebral edema or effusions 
(mostly asymptomatic) occurred with donanemab.
CONCLUSIONS: In patients with early Alzheimer's disease, donanemab resulted in a 
better composite score for cognition and for the ability to perform activities 
of daily living than placebo at 76 weeks, although results for secondary 
outcomes were mixed. Longer and larger trials are necessary to study the 
efficacy and safety of donanemab in Alzheimer's disease. (Funded by Eli Lilly; 
TRAILBLAZER-ALZ ClinicalTrials.gov number, NCT03367403.).