Donanemab (Kisunla)

Donanemab is a humanised IgG1 monoclonal antibody directed against the pyroglutamate-modified N-terminus of amyloid-beta (N3pG), an epitope found almost exclusively in established plaques. In the phase 3 TRAILBLAZER-ALZ 2 trial it slowed clinical decline by 22 to 36 percent on the Integrated Alzheimer Disease Rating Scale and CDR-SB over 76 weeks in early symptomatic Alzheimer disease, with greater effect in low/medium tau participants. Treatment can be stopped once amyloid clearance is achieved on PET. The FDA approved donanemab on 2 July 2024. The European Medicines Agency initially refused approval on 27 March 2025 but recommended approval after re-examination on 24 July 2025, and the European Commission granted marketing authorisation on 24 September 2025, restricted to APOE epsilon-4 non-carriers and heterozygotes. ARIA-E occurred in roughly 24 percent of treated participants in TRAILBLAZER-ALZ 2. On 9 July 2025 the FDA approved an updated label with a modified titration schedule that lowered ARIA-E rates. UK MHRA approved donanemab on 23 October 2024 (NICE issued final non-recommendation on 19 June 2025); Japan's PMDA approved donanemab on 24 September 2024.