Accelerated Approval Request Initiated for Lecanemab for Treatment of Alzheimer Disease

A rolling biologics license application (BLA) has been initiated for lecanemab (BAN2401; Biogen, Cambridge, MA) for the treatment of early Alzheimer disease (AD). The BLA is being submitted to the Food and Drug Administration (FDA) via the accelerated approval pathway and is primarily based on clinical data from Study 201. The Study 201 phase 2b trial results demonstrated a high degree of amyloid  (Aβ) plaque lowering and consistent reduction of clinical decline. 

Study 201 was a proof-of-concept study in 856 participants with mild cognitive impairment (MCI) due to AD and mild AD with confirmed presence of Aβ pathology. After 18 months of treatment, 10 mg/kg biweekly lecanemab reduced brain Aβ from a baseline mean 1.37 SUVr units to a mean 0.306 SUVr units, which began as early as 3 months. Significant A reduction relative to placebo was maintained while off-treatment over a gap period.

The reduction in A correlated with slower clinical decline on AD Composite Score (ADCOMS), Clinical Dementia Rating-Sum-of-Boxes (CDR-SB), and AD Assessment Scale-Cognitive Subscale (ADAS-cog) at the treatment group and patient level. As published in Alzheimer Research and Therapy, in Study 201 there was a 64% likelihood of probability for lecanamab to improve ADCOMS scores by 25% compared with placebo. This did not meet the prespecified 80% threshold that had been prespecified, and thus was not statistically significant, however. Improvement in clinical symptoms was also observed on the CDR-SB and ADAS-cog, which were secondary endpoints.
 
“The Alzheimer community welcomes scientific innovation that creates more treatment options for people living with this terrible neurodegenerative disease,” said Jeffrey Cummings, MD, ScD, lecanemab manuscript author and director at the Chambers-Grundy Center for Transformative Neuroscience, University of Nevada Las Vegas. “Based on the efficacy and safety results of the Phase 2b study and preliminary results from the open-label extension study, I am optimistic about the potential lecanemab may have as a treatment choice for patients with early Alzheimer’s to ameliorate the otherwise inevitable decline they face.”

The rate of the adverse event amyloid-related imaging abnormalities-edema (ARIA-E) (ie, brain swelling) after lecanemab treatment 10 mg/kg biweekly dosing was 9.9%.