Anti-Amyloid Immunotherapy (IgG1 — Targets Pyroglutamate-Modified Amyloid-β) Pregnancy: Not applicable. Avoid in women of childbearing potential.

Donanemab (Anti-Amyloid Monoclonal Antibody)

Brand names: Kisunla

Adult dose

Dose: 700 mg IV over 30 min (first 3 doses); then 1400 mg IV every 4 weeks until amyloid clearance confirmed on PET

Route: IV infusion

Frequency: Every 4 weeks (after initial 3 monthly doses)

Max: 1400 mg per infusion

Unique feature: treatment stops once amyloid clearance is achieved on PET scan — unlike lecanemab (which is continuous). FDA approved July 2024. Under MHRA review 2024. Targets N-terminal pyroglutamate-modified Aβ deposits (insoluble plaques specifically).

Paediatric dose

Route:

Not applicable.

Dose adjustments

Renal

No dose adjustment required in mild-moderate renal impairment.

Hepatic

No dose adjustment required.

Clinical pearls

TRAILBLAZER-ALZ 2 (Sims et al. NEJM 2023): donanemab vs placebo in early symptomatic AD — 35% slower cognitive decline on iADRS composite score in low/medium tau group; statistically significant. In high tau group: less benefit — suggests optimal window is early disease with lower tau burden
Amyloid clearance endpoint: 52% of donanemab patients achieved amyloid clearance (defined as <24.1 Centiloid on PET) by 76 weeks and stopped treatment — novel 'treat-to-target' approach. Long-term outcome after stopping unclear
Tau staging matters: TRAILBLAZER-ALZ 2 stratified by tau PET burden — patients with high tau showed less benefit; implies staging by both amyloid AND tau before prescribing is optimal practice
Comparison with lecanemab: donanemab targets insoluble plaque deposits specifically; lecanemab targets soluble protofibrils. Both show similar magnitude of efficacy (~25–35% slowing); donanemab has higher ARIA rate but allows treatment discontinuation once clearance achieved

Contraindications

APOE4 homozygotes (highest ARIA risk)
Active anticoagulation (increased ARIA-H risk)
Recent stroke or intracranial surgery

Side effects

ARIA-E: 24% in TRAILBLAZER-ALZ 2 (higher than lecanemab — dose titration mitigates)
ARIA-H: 31% microhaemorrhages/siderosis
Serious ARIA: 1.6% (vs 0.8% placebo)
Three deaths potentially ARIA-related in trial
Infusion reactions (first few infusions)
Headache

Interactions

Anticoagulants and antiplatelets (significantly increased ARIA-H risk)
MRI-incompatible devices (monitoring barrier)

Monitoring

MRI brain (before each dose for first 3 doses; then every 6 months — ARIA monitoring)
Amyloid PET at approximately 6 and 12 months (treatment stop criterion)
APOE4 genotyping before initiation
Cognitive assessments (iADRS, CDR-SB)
Infusion-related reaction monitoring

Reference: BNFc; Sims et al. NEJM 2023 (TRAILBLAZER-ALZ 2); FDA Prescribing Information Kisunla 2024; Alzheimer's Association 2024 guidelines; BNF 90 (MHRA review pending). Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways