Eisai, in collaboration with BioArctic, has completed a rolling submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for a subcutaneous autoinjector version of lecanemab-irmb (Leqembi). This new formulation is intended for weekly maintenance dosing in patients with Mild Cognitive Impairment (MCI) or mild dementia stage Alzheimer's disease (AD). The FDA had previously granted Fast Track designation to this application.
The BLA is supported by data derived from the Clarity AD open-label extension (OLE) study, combined with modeling of observed data. The subcutaneous autoinjector is designed for convenient administration at home or in medical facilities, with an injection time of approximately 15 seconds. This offers a potentially less burdensome alternative to the current bi-weekly intravenous (IV) initiation phase, followed by monthly IV maintenance dosing. The FDA accepted Eisai’s Supplemental Biologics License Application (sBLA) for monthly Leqembi IV maintenance dosing in June 2024 and set a PDUFA action date for January 25, 2025.
The subcutaneous 360 mg weekly maintenance regimen aims to sustain effective drug concentrations, thereby continuing the clearance of neurotoxic protofibrils even after amyloid-beta (Aβ) plaque has been cleared from the brain. This is based on the understanding that AD is a continuous neurotoxic process that extends beyond plaque deposition, and early, continuous treatment may prolong benefits.
This subcutaneous autoinjector is anticipated to be more user-friendly for patients and their caregivers, potentially decreasing the necessity for frequent hospital visits and intensive nursing care compared to IV administration. Beyond the convenience factor, subcutaneous maintenance dosing may also help in maintaining clinical and biomarker benefits achieved during the initial treatment phases.
Leqembi, a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody, targets aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). It is currently approved in the U.S., Japan, China, South Korea, Hong Kong, Israel, UAE, and Great Britain for treating MCI due to AD and mild AD dementia. These approvals were largely based on Phase 3 data from Eisai’s Clarity AD clinical trial, which demonstrated statistically significant results in meeting its primary endpoint and all key secondary endpoints. Common adverse events associated with lecanemab include infusion reactions, ARIA-H (combined cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis), ARIA-E (edema/effusion), headache, and fall.
Eisai has also submitted applications for lecanemab approval in 10 other countries and regions, including the European Union (EU). Furthermore, Eisai's Phase 3 clinical study (AHEAD 3-45) is ongoing for individuals with preclinical AD, and the Tau NexGen clinical study for Dominantly Inherited AD (DIAD) includes lecanemab as the backbone anti-amyloid therapy.
