Donanemab for Alzheimer’s Disease: A Systematic Review of Clinical Trials

Abstract

Amyloid-β (Aβ) plaques and aggregated tau are two core mechanisms that contribute to the clinical deterioration of Alzheimer’s disease (AD). Recently, targeted-Aβ plaque reduction immunotherapies have been explored for their efficacy and safety as AD treatment. This systematic review critically reviews the latest evidence of Donanemab, a humanized antibody that targets the reduction in Aβ plaques, in AD patients. Comprehensive systematic search was conducted across PubMed/MEDLINE, CINAHL Plus, Web of Science, Cochrane, and Scopus. This study adhered to PRISMA Statement 2020 guidelines. Adult patients with Alzheimer’s disease being intervened with Donanemab compared to placebo or standard of care in the clinical trial setting were included. A total of 396 patients across four studies received either Donanemab or a placebo (228 and 168 participants, respectively). The Aβ-plaque reduction was found to be dependent upon baseline levels, such that lower baseline levels had complete amyloid clearance (<24.1 Centiloids). There was a slowing of overall tau levels accumulation as well as relatively reduced functional and cognitive decline noted on the Integrated Alzheimer’s Disease Rating Scale by 32% in the Donanemab arm. The safety of Donanemab was established with key adverse events related to Amyloid-Related Imaging Abnormalities (ARIA), ranging between 26.1 and 30.5% across the trials. There is preliminary support for delayed cognitive and functional decline with Donanemab among patients with mild-to-moderate AD. It remains unclear whether Donenameb extends therapeutic benefits that can modify and improve the clinical status of AD patients. Further trials can explore the interplay between Aβ-plaque reduction and toxic tau levels to derive meaningful clinical benefits in AD patients suffering from cognitive impairment.