Lecanemab, an Antibody to Amyloid Beta, Reduced Amyloid Levels and Cognitive Decline

Preliminary assessment of results clinical trials of lecanemab (BAN2401; Biogen, Cambridge, MA; Eisai, Tokyo, Japan) for potential treatment of Alzheimer disease (AD), were presented at the Alzheimer’s Association International Conference July 26-30, 2021.

Lecanemab reduced brain amyloid beta (Aβ) and slowed clinical decline in an 18-month phase 2b proof-of-concept study (NCT01767311) in early AD. In an open-label extension (OLE) of this study, those who received placebo or lecanemab were both treated with lecanemab. Reduced clinical decline relative to natural disease progression ws seen in both groups.  

The adjusted mean change from on the AD Composite Score (ADCOMS) from baseline of the open-label period to 18 months was 0.102, 0.165, and 0.07 for those who received lecanemab 10 mg/kg twice per month, lecanemab 10 mg/kg once per month, or placebo in the blinded portion of the trial, respectively. These levels reflect a slower rate of disease progression compared with 0.214 seen in the natural cohort in the Alzheimer’s Disease Neuroimaging Initiative (ADNI).  

“The findings from the lecanemab phase 2b OLE study are encouraging as they supply further insights into outcomes with anti-amyloid therapies and we look forward to learning more in the phase 3 studies, Clarity AD and AHEAD 3-45, currently underway,” said Lynn Kramer, MD, chief clinical officer, neurology business group, Eisai.

Lecanemab is an investigational humanized monoclonal antibody that preferentially binds to soluble Aβ aggregates (protofibrils). After analysis of the core study, there was an off-treatment gap period of 9-59 months (period of time between the last dose of lecanemab in the core and the OLE baseline; an average of 24 months). 

Similar results were observed for Clinical Dementia Rating—Sum of Boxes (CDR-SB) and AD Assessment Scale—Cognitive Subscale (ADAS-Cog). The results support the concept of increased long-term benefit of continued treatment with lecanemab when initiated in the early AD stage.