Still grasping at straws: donanemab in Alzheimer’s disease

Abstract

ABSTRACT Introduction Alzheimer’s disease is the leading cause of disability and poor health, takes a huge emotional and financial burden on family caregivers, and is costly. Donanemab (LY3002813) is a new monoclonal antibody that uniquely targets Aβ(p3-42), a pyroglutamate form of Amyloid-β (Aβ) exclusively found in plaques. Areas covered The phase 2 trial of donanemab in participants with early symptomatic Alzheimer’s disease, TRAILBLAZER-ALZ. Donanemab reduced cerebral plaque but not tau load and only marginally improved the primary outcome of cognition and activities of daily living (p = 0.04) without altering individual measures of these. Expert opinion In TRAILBLAZER-ALZ, anticholinesterase use was given at the beginning but not the end of the trial, and thus, it is not known whether changes in this or other medicines were involved in the outcome with donanemab. Tau load (measured with flortuacipir PET) may be a biomarker of cognition but was not altered by donanemab. As there is no clear evidence that removing cerebral amyloid plaques with Aβ antibodies, such as donanemab, improves cognition and the activities of daily living in Alzheimer’s disease, clinical trials with these agents should be abandoned, and more time and money should spend on further investigating the underlying cause of Alzheimer’s disease.