Balancing benefit and risk in early Alzheimer's disease: the European Medicines Agency (EMA) assessment of lecanemab and donanemab.

Abstract

Alzheimer's disease (AD) remains the leading cause of dementia in Europe, with limited therapeutic options despite decades of research. Recent regulatory approvals of lecanemab and donanemab in the EU mark a significant milestone. Both antibodies, developed within the amyloid hypothesis, demonstrated statistically significant effects on cognitive and functional outcomes in patients with early AD, though the clinical meaningfulness of these effects remains debated. There are also important safety concerns, particularly amyloid-related imaging abnormalities (ARIA), which resulted in difficult benefit-risk assessments. The Personal View describes some of the lines of evidence considered by the European Medicines Agency in the assessment of efficacy of these medicines, and some of the measures to ensure their safe use. While these therapies do not halt disease progression, and have substantial risks, they represent a step toward more transformative treatments. Future research, including real-world evidence studies, should refine patient selection, optimise monitoring, and explore combination approaches and new targets to achieve improved outcomes.