Donanemab (Kisunla)
Donanemab (Kisunla) received full FDA approval in 2024 for early symptomatic Alzheimer disease based on the TRAILBLAZER-ALZ 2 trial. It is distinguished by amyloid-clearance–based stopping rules that allow treatment discontinuation once plaque clearance is achieved.
- Mechanism of action
- Humanized IgG1 monoclonal antibody targeting N-truncated pyroglutamate amyloid-beta, a modified form predominantly found in amyloid plaques.
- Administration route
- Intravenous infusion every 4 weeks
FDA-approved indications (2026)
Early Alzheimer disease
MCI or mild dementia stage of AD with confirmed amyloid pathology.
Dosing: adult, renal, and hepatic
| Population | Dose |
|---|---|
| Induction | 700 mg IV every 4 weeks × 3 doses, then 1400 mg IV every 4 weeks. |
| Stopping rule | Consider discontinuation based on PET-confirmed amyloid clearance (label-specified thresholds). |
| Hepatic / renal | No specific adjustment; limited data. |
Contraindications and boxed warnings
Contraindications
- Serious hypersensitivity to donanemab.
Boxed warnings
- ARIA-E and ARIA-H, including rare fatal events, particularly in APOE4 homozygotes.
2026 guideline and pivotal trial position
AAN 2025 appropriate-use guidance and Alzheimer Association 2025 statements position donanemab and lecanemab as similar in overall role — disease-modifying therapy for biomarker-confirmed early AD — while noting different dosing intervals, stopping rules (donanemab) and ARIA patterns. Pre-treatment MRI and APOE4 genotyping are expected standard of care.
TRAILBLAZER-ALZ 2 (2023)
Significant slowing of clinical decline (iADRS) over 18 months; greater effect in low/medium tau subgroup.
Cross-system reasoning
Donanemab's tau-stratified benefit magnifies the role of neuroimaging and biomarker workup: amyloid PET or CSF for eligibility, tau PET for prognosis, serial MRI for ARIA surveillance. Coordination with cardiology is essential where anticoagulation is considered, given the risk profile. Its stopping rule introduces a novel treatment-discontinuation discussion uncommon in chronic neurology.
Key references
Related clinical reading
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This reference is for US-licensed physicians and is not a substitute for the full FDA prescribing information. Dosing in special populations, drug interactions, and emerging safety information should be verified against the current manufacturer label and society guidelines before prescribing.