Pathophysiological biomarker–based clinical development of lecanemab (BAN2401), anti–Aβ protofibril antibody

Abstract

Lecanemab is a humanized IgG1 monoclonal antibody that preferentially targets soluble aggregated Aβ species (oligomers, protofibrils) and insoluble fibrils. In a phase II proof of concept study in early Alzheimer disease, lecanemab 10mg/kg bi–weekly treatment reduced amyloid PET SUVr and slowed clinical decline. In the CSF substudy, lecanemab showed reduction of CSF p–tau181, neurogranin, and slowed increase of Neurofilament light chain which are biomarkers of tau pathophysiology, synaptic dysfunction, and axon degeneration, respectively. An Open label extension (OLE) with 10mg/kg biweekly lecanemab dosing was implemented after analysis of the Core study, enrolling 180 subjects, with an intervening Gap period off–treatment of 9–59 months (mean 24 months). Amyloid PET SUVr level maintained over the gap period and further reduced with retreatment of lecanemab. Lecanemab showed amyloid reduction and slowing of clinical decline, reduced or slowed increase of CSF AD biomarkers indicating that lecanemab inhibits downstream AD pathophysiology by removing brain amyloid.