Donanemab Yields Reduced Cognitive Decline in Early Alzheimer’s Disease

Early findings suggest donanemab may slow cognitive decline in Alzheimer’s disease, according to results of a randomized, phase 2 trial (N Eng J Med. 2021 Mar 13. Epub ahead of print).

A hallmark of Alzheimer’s disease is the accumulation of amyloid-β (Aβ) peptide,” wrote Mark A. Mintun, MD, Eli Lilly and Company, and co-investigators on the importance of investigating donanemab, an antibody that targets a modified form of Aβ, as a potential treatment of early Alzheimer’s disease.

A total of 257 patients with early symptomatic Alzheimer’s disease, as well as tau and amyloid deposits on positron-emission tomography (PET), were enrolled in the phase 2 trial. Patients were randomized 1:1 to receive donanemab (n=131) or placebo (n=126) intravenously every 4 weeks for up to 72 weeks.

The primary endpoint was change from baseline score on the Integrated Alzheimer’s Disease Rating Scale at 76 weeks, as measured from 0 to 144, with lower scores indicating greater cognitive and functional impairment.

The baseline iADRS score was 106 in both trial arms. At 76 weeks, the change from baseline iADRS score in the donanemab arm was assessed to be -6.86 versus -10.06 in the placebo arm (3.20, 95%CI, 0.12 to 6.27; P=0.04).

Secondary endpoints of the trial included the change in the amyloid and tau burden on PET as well as changes in scores on the Clinical Dementia Rating-Scare- Sum of Boxes, Alzheimer’s Disease Assessment Scale, the Alzheimer’s Disease Cooperative Study-Instrument Activities of Daily Living Inventory, and the Mini-Mental State Examination.

Notably, reductions in the amyloid plaque level and tau load were 85.06 centiloads and 0.01 greater, respectively, in the donanemab arm than in the placebo arm at 76 weeks. Results for the other secondary outcomes showed no substantial difference between treatment arms.

Researchers observed amyloid-related cerebral edema or effusions in the donanemab arm, noting most were asymptomatic.

Dr Mintun et al concluded, “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.

Further research into the efficacy and safety of donanemab for treatment of early Alzheimer’s disease through additional and expanded clinical trials is warranted.—Kaitlyn Manasterski