Donanemab in Early Alzheimer's Disease.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 33720637 · doi:10.1056/NEJMoa2100708
What was done
A multicenter phase 2 randomized controlled trial evaluated donanemab (an antibody targeting deposited amyloid-beta) versus placebo in 257 patients with early symptomatic Alzheimer's disease confirmed by tau and amyloid PET deposition. Participants were randomized 1:1 to receive intravenous donanemab (700 mg for 3 doses, then 1400 mg every 4 weeks; n = 131) or placebo (n = 126) for up to 72 weeks. The primary outcome was the change from baseline to 76 weeks on the Integrated Alzheimer's Disease Rating Scale (iADRS; range 0 to 144). Secondary clinical outcomes included CDR-SB, ADAS-Cog13, ADCS-iADL, and MMSE, along with PET amyloid and tau burden.
What was found
Baseline iADRS was 106 in both arms. At 76 weeks, iADRS declined by 6.86 points with donanemab versus 10.06 points with placebo (difference 3.20; 95% CI, 0.12 to 6.27; P = 0.04). Most secondary clinical outcomes showed no substantial difference between groups. Amyloid plaque reduction was 85.06 centiloids greater and global tau load reduction was 0.01 greater with donanemab than placebo at 76 weeks. Amyloid-related cerebral edema or effusions (mostly asymptomatic) occurred in the donanemab group.
Why it matters
This study shows that antibody-mediated clearance of deposited amyloid-beta can produce modest slowing of composite cognitive-functional decline over 76 weeks in early Alzheimer's disease.
Limits
The sample size was modest (n = 257) and follow-up was limited to 76 weeks. Most secondary clinical outcomes did not show statistically significant differences, the primary endpoint confidence interval was wide with a lower bound near zero, and treatment was associated with amyloid-related cerebral edema or effusions.
Cited by
- supports Eli Lilly's monoclonal antibody donanemab was shown to slow the decline of Alzheimer's disease by 32%.