Lecanemab (Leqembi)

Lecanemab is a humanised IgG1 monoclonal antibody that binds soluble amyloid-beta protofibrils and, to a lesser degree, fibrillar plaques. In the phase 3 CLARITY-AD trial it slowed decline on the Clinical Dementia Rating Sum of Boxes by 0.45 points over 18 months in early Alzheimer disease versus placebo. The FDA granted accelerated approval on 6 January 2023 and traditional approval on 6 July 2023. The European Medicines Agency initially refused the marketing authorisation in July 2024 but reversed after re-examination, and the European Commission granted approval on 15 April 2025, restricted to APOE epsilon-4 non-carriers and heterozygotes. The main safety concern is amyloid-related imaging abnormalities (ARIA-E oedema, ARIA-H microhaemorrhage), which are markedly more frequent and severe in APOE epsilon-4 homozygotes. On 30 August 2025 the FDA approved a once-weekly subcutaneous autoinjector formulation (LEQEMBI IQLIK) for maintenance dosing, the first anti-amyloid antibody with at-home administration. NICE issued final guidance on 19 June 2025 not recommending lecanemab for routine NHS use, with a third consultation opened in 2026; Germany's G-BA found kein Zusatznutzen on 19 February 2026.