To provide updated efficacy and safety results from the lecanemab phase 2 study, including data on the longitudinal plasma Aβ 42/40 ratio (C2N PrecivityAD assay) and the relationship to longitudinal amyloid PET in the core, gap period, and OLE.

Lecanemab (BAN2401), a humanized IgG1 monoclonal antibody, preferentially binds large soluble aggregated Aβ species and has demonstrated robust brain fibrillar amyloid reduction correlating with slowing clinical decline in early AD (Swanson et al. Alz Res Therapy 13; 2021). 

The lecanemab Study 201 Core was a randomized placebo controlled study in which 856 patients were randomized to five dose regimens or placebo. An open-label extension (OLE) of Study 201, was initiated to allow patients to receive open-label lecanemab 10mg/kg-biweekly for up to 24 months, with an intervening off-treatment period (gap period) ranging from 9-59 months (mean 24 months). 

Treatment differences vs placebo at 18 months in the core were maintained across 3 clinical assessments at OLE baseline. The rates of progression during the gap were similar in lecanemab and placebo patients. In the OLE, progression on all clinical endpoints plateaued with lecanemab for patient with OLE baseline global CDR 0.5 or 1, while those with global CDR >1 continued to progress, though less than a comparative natural disease progression rate (ADNI). Lecanemab produced dose-dependent reductions in PET SUVr, with corresponding increases in plasma Aβ 42/40 ratio in core and OLE. Consistent with core safety findings, lecanemab was well-tolerated with <10% incidence of ARIA-E at 10-mg/kg biweekly in the OLE.

Findings from the lecanemab study 201 suggest that continued treatment may be beneficial for subjects with early AD. These data are hypothesis generating and will be further explored in ongoing phase 3 lecanemab clinical trials in early AD and preclinical AD (Clarity AD and AHEAD 3-45, respectively).