Eisai Begins Rolling BLA Submission of Lecanemab for Early Alzheimer Disease

Eisai has initiated a rolling submission to the Food and Drug Administration for its Biologics License Application for lecanemab (BAN2401), an investigational anti-amyloid beta protofibril antibody, for the treatment of early Alzheimer disease.

The submission is supported by data from a randomized, double-blind, phase 2b trial (ClinicalTrials.gov Identifier: NCT01767311) that evaluated lecanemab in 856 patients with mild cognitive impairment due to Alzheimer disease and mild Alzheimer disease with confirmed presence of amyloid pathology. At 18 months, treatment with lecanemab at the highest doses (10mg/kg biweekly) reduced brain amyloid by 0.306 SUVr units from a baseline mean of 1.37; over 80% of patients became amyloid negative by visual read. 

Findings also showed that reductions in brain amyloid correlated with improvements in cognitive decline based on the Alzheimer Disease Composite Score, the Clinical Dementia Rating-Sum-of-Boxes, and the Alzheimer Disease Assessment Scale-Cognitive Subscale. The incidence of amyloid-related imaging abnormalities-edema/effusion was 9.9% for the 10mg/kg biweekly dose.

After completion of the proof-of-concept trial, 180 patients were assessed in the phase 2b open-label extension study. All patients received lecanemab 10mg/kg biweekly. Results confirmed that lecanemab reduced amyloid PET SUVr with significant reduction occurring as early as 3 months; over 80% of patients achieved amyloid negative status by visual read as early as 12 months. The incidence of amyloid-related imaging abnormalities-edema/effusion was consistent for the 10mg/kg biweekly dose at approximately 10%.

“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,” said Jeffrey Cummings, MD, ScD, lecanemab manuscript author and director at the Chambers-Grundy Center for Transformative Neuroscience, University of Nevada Las Vegas.

Lecanemab is currently being investigated in the phase 3 Clarity AD study (ClinicalTrials.gov Identifier: NCT03887455) in 1795 patients with early Alzheimer disease; the study has completed enrollment as of March 2021. It is also being evaluated in the phase 3 AHEAD 3-45 study (ClinicalTrials.gov Identifier: NCT04468659) in individuals with preclinical Alzheimer disease, defined as patients who are clinically normal but have intermediate or elevated levels of amyloid in the brain.

Reference

Eisai initiates rolling submission for the US FDA Biologics License Application of lecanemab for early Alzheimer’s disease under the accelerated approval pathway. News release. BioArctic. Accessed September 28, 2021. https://www.eisai.com/news/2021/news202177.html.