Drug Development

Alzheimer's disease is a progressive neurodegenerative disorder that affects memory, thinking, and behavior, leading to a decline in cognitive function over time. This study aims to investigate the efficacy and safety of Donanemab to improve cognitive and behavioral symptoms in people living with Alzheimer's disease.

We systematically searched in Cochrane, PubMed, Web of Science and SCOPUS since date of inception until Dec 1^st 2024. Due to limitations in the available data, a meta-analysis was not conducted for this study. Instead, a synthetic approach was utilized to summarize and interpret the findings.

We initially identified 477 studies through database search and included only five studies in the systematic review, included studies showed a total of 2205 participants (1249 females, 56.64 %), 1133 participants received the drug and 1072 received placebo. The mean age ranged from 66.8 to 78.3 years. After dosing, a marked positive change of brain amyloid level without significant reaccumulation for up to 72 weeks was observed among patients receiving three to five doses of 10 mg/kg Donanemab. No significant amyloid reduction was seen in the lower Donanemab multiple dose levels (0.3 to 3mg/kg). To assess the efficacy and adverse effects of donanemab, we observed a significant increase in musculoskeletal disorders, specifically arthralgia, in both the intervention and control groups. Cerebral microhemorrhage showed a notable rise, predominantly in the intervention group compared to the control. Similarly, superficial siderosis increased markedly in the intervention group. Additionally, fatigue, falls, and headaches were reported with a marked increase across both groups at varying doses.

Donanemab demonstrated a rapid, robust, and sustained reduction in brain amyloid plaque with no significant reaccumulation observed at 72 weeks. It was generally well-tolerated at doses up to 10 mg/kg; however, its use is associated with significant adverse effects, highlighting the need for careful risk-benefit evaluation.