Researchers from Eli Lilly found that donanemab therapy modestly slowed cognition and functionality decline among patients with early Alzheimer disease (AD). These findings were published in The New England Journal of Medicine.
Patients (N=257) with early symptomatic AD were recruited at 56 sites in the United States and Canada for the TRAILBLAZER-ALZ randomized, double-blind phase 2 trial. Randomized in a 1:1 ratio, patients received 3 doses of 700 mg then 1400 mg donanemab (n=131) or placebo (n=126) every 4 weeks for 72 weeks.
Patients underwent florbetapir positron-emission tomography (PET) scans and were evaluated by the instruments Integrated AD Rating Scale (iARDS), Mini-Mental State Examination (MMSE), AD Assessment Scale (ADAS-Cog13), AD Cooperative Study-Instrumental Activities of Daily Living Inventory (ADCS-iADL), and Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB).
Patients in the intervention and control groups were aged mean 75.0 and 75.4 years, 51.9% and 51.6% were women, 93.1% and 96.0% were White, baseline iARDS scores were 106.2 and 105.9, MMSE was 23.6 and 23.7, CDR-SB was 3.6 and 3.4, and amyloid plaque levels were 107.6 and 101.1 centiloids, respectively.
At week 76, iARDS scores changed by -6.86 among the donanemab and -10.06 among the placebo recipients (difference, 3.20; 95% CI, 0.12-6.27; P =.04). Compared with the placebo group, CDR-SB scores changed by -0.36 (95% CI, -0.83 to 0.12), ADAS-Cog13 by -1.86 (95% CI, -3.63 to 0.09), ADCS-iADL by 1.21 (95% CI, -0.77 to 3.20), and MMSE by 0.64 (95% CI, -0.40 to 1.67) among the intervention cohort.
During PET scan, florbetapir was -84.13 centiloids among the donanemab and 0.93 centiloids among the control recipients. At weeks 28 and 56, 27.4% and 54.7% of patients receiving donanemab had sufficient lowering of amyloid plaque levels which justified switching to a placebo infusion, respectively.
At least 1 adverse effect was reported by 90.8% of the intervention and 90.4% of the placebo groups. Amyloid-related imaging abnormalities with edema or effusions were more common among the intervention cohort (26.7% vs 0.8%). Antidrug antibodies were detected among 90% of donanemab recipients.
This study was limited by the heterogeneity of drug dosing, as many patients were given a reduced dose due to changes in amyloid plaque.
The study authors concluded donanemab modestly reduced cognitive and functional decline among patients with symptomatic early AD. Long-term outcomes have yet to be elucidated.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Mintun MA, Lo AC, Evans CD, et al. Donanemab in early Alzheimer’s disease. N Engl J Med. Published online May 6, 2021. doi:10.1056/NEJMoa2100708