Robert Lai (United Kingdom)
Eisai Ltd, Inc NBGAuthor Of 1 Presentation
LECANEMAB, AN ANTI-AΒ PROTOFIBRIL ANTIBODY: UPDATED DATA FROM A RANDOMIZED, DOUBLE-BLIND PHASE 2B PROOF OF CONCEPT CLINICAL TRIAL AND OPEN-LABEL EXTENSION IN EARLY ALZHEIMER’S DISEASE
- Chad J. Swanson (United States of America)
Abstract
Background and Aims:
Lecanemab (BAN2401) preferentially targets soluble aggregated amyloid beta (Aβ). Herein, we provide updated efficacy, safety and pharmacokinetic/dynamic data from a phase 2 trial (Core) and an open-label extension (OLE) assessing lecanemab in early Alzheimer’s disease (AD).
Methods:
This trial utilized a Bayesian design with response-adaptive randomization to assess 6 lecanemab dosing regimens versus placebo in early AD, defined as mild cognitive impairment due to AD and mild AD dementia. The primary endpoint was Bayesian analysis at 12-months on the Alzheimer’s Disease Composite Score (ADCOMS). Secondary endpoints included 18-month analyses of PET brain amyloid reduction; clinical decline on ADCOMS, CDR-SB, & ADAS-cog14. An ongoing OLE was initiated following the Core study where consenting subjects receive 10 mg/kg biweekly for up to 60 months.
Results:
854 randomized subjects were treated (lecanemab:609; placebo:245). At 12 months, the 10-mg/kg biweekly ED90 dose showed a 64% probability to be better than placebo by 25% on ADCOMS, which missed the 80% threshold for the primary outcome. At 18 months, 10-mg/kg biweekly lecanemab reduced brain amyloid (-0.306 SUVr units) while improving ADCOMS (30%), ADAS-cog14 (26%), and CDR-SB (26%) versus placebo. Lecanemab was well-tolerated with <10% incidence of ARIA-E at 10-mg/kg biweekly. A similar profile has been observed in 180 subjects who have been dosed in the OLE.
Conclusions:
Lecanemab was well tolerated and demonstrated reduction in brain amyloid along with consistent reduction of clinical decline across several endpoints in the Core study and a similar profile in the ongoing OLE. A Phase 3 study (ClarityAD) is underway.