How do lecanemab and donanemab compare for Alzheimer's?

Short Answer: Both are anti-amyloid monoclonal antibodies that modestly slow cognitive decline (~27-35%). Donanemab may clear amyloid faster, allowing treatment discontinuation, while lecanemab requires ongoing infusions. Both carry ARIA (brain swelling/bleeding) risk.

Evidence Level: strong

Detailed Answer

Lecanemab (Leqembi) and donanemab (Kisunla) represent the first Alzheimer's drugs to show consistent amyloid clearance and clinical benefit. Lecanemab targets soluble amyloid protofibrils and showed 27% slowing of decline in the Clarity AD trial (van Dyck et al., 2023, NEJM). Donanemab targets pyroglutamate-modified amyloid (N3pG-Aβ) — an early plaque form — and showed 35% slowing in the TRAILBLAZER-ALZ 2 trial, with 47% of patients completing amyloid clearance and stopping treatment. ARIA (amyloid-related imaging abnormalities) occurred in ~24% (lecanemab) and ~37% (donanemab) of patients, with higher risk in APOE4 homozygotes. Key differences: donanemab may allow finite treatment duration; lecanemab is biweekly infusions indefinitely. Both cost ~$26,000-$32,000/year. Neither reverses cognitive decline — they slow progression by months to a year.

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