Lecanemab’s safety in the CLARITY AD open-label extension: a preliminary update including subcutaneous formulation

<h3>Background</h3> Intravenous (IV) lecanemab slows progression of Alzheimer’s disease (AD) but has been associated with amyloid-related imaging abnormalities. A subcutaneous (SC) formulation is being developed to improve lecanemab’s safety. We provide an update on the safety profile of lecanemab IV focusing on neutralising antibodies (Nab) and anti-drug antibodies (ADA) and a preliminary safety update on the SC formulation. <h3>Methods</h3> Clarity AD is a Phase 3 study with an optional open-label extension (OLE) in patients with early AD. Eligible patients were randomised to placebo or lecanemab 10 mg/kg biweekly IV. Clinical assessments included Clinical Dementia Rating-Sum-of-Boxes and AD Assessment Scale-Cognitive Subscale 14. ADA and NAb assays were performed using a tiered approach. Lecanemab SC is being assessed in a substudy of the OLE. <h3>Results</h3> The incidence of treatment-emergent ADA for IV lecanemab was 5.5% in the core study and 5.7% in OLE. The incidence of treatment-emergent NAb was 4.1% in the core study. ADA and NAb status did not meaningfully affect lecanemab serum concentration nor the slowing of cognitive decline relative to placebo. Preliminary safety results on the SC formulation will be presented. <h3>Conclusions</h3> Lecanemab exhibits minimal immunogenic risk. Ongoing studies will confirm the safety and efficacy profiles of SC lecanemab.