Eisai has finalized the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for a subcutaneous formulation of Leqembi (lecanemab-irmb). This new formulation is designed for weekly maintenance dosing via an autoinjector, offering a potentially more convenient administration route for patients with early Alzheimer's disease (AD). The FDA had previously granted Fast Track designation to this application.
The BLA is based on data derived from the Clarity AD open-label extension (OLE) study, combined with modeling of observed data. The subcutaneous autoinjector is intended for patients who have completed the bi-weekly intravenous (IV) initiation phase of Leqembi treatment. The weekly subcutaneous doses aim to maintain effective drug concentrations, thereby sustaining the clearance of neurotoxic protofibrils, which contribute to neuronal injury even after amyloid-beta (Aβ) plaques are removed from the brain.
Potential Benefits of Subcutaneous Administration
The shift to subcutaneous administration offers several potential advantages. Eisai anticipates that the autoinjector will be easier for patients and their caregivers to use, potentially reducing the need for frequent hospital visits and extensive nursing care compared to IV infusions. The injection process is expected to take approximately 15 seconds. Beyond convenience, maintaining consistent drug levels through weekly dosing may prolong the clinical and biomarker benefits observed with Leqembi.
Leqembi's Current Status and Ongoing Studies
Leqembi is currently approved for the treatment of Alzheimer's disease in patients with Mild Cognitive Impairment (MCI) or mild dementia in the U.S., Japan, China, South Korea, Hong Kong, Israel, UAE, and Great Britain. Eisai has also submitted applications for approval in 10 other countries and regions, including the European Union. The FDA has already accepted Eisai's supplemental BLA (sBLA) for monthly Leqembi IV maintenance dosing, with a PDUFA action date set for January 25, 2025.
Lecanemab is the product of a collaboration between BioArctic and Eisai. BioArctic originally developed the antibody based on the discovery of the Arctic mutation in Alzheimer's disease by Professor Lars Lannfelt. Eisai is responsible for clinical development, regulatory submissions, and commercialization of lecanemab. BioArctic retains the right to commercialize lecanemab in the Nordic region.
Clinical Trial Data and Safety Profile
Leqembi's approvals are based on Phase 3 data from the Clarity AD clinical trial, where it met its primary endpoint and key secondary endpoints with statistically significant results. Common adverse events included infusion reactions, ARIA-H (combined cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis), ARIA-E (edema/effusion), headache, and falls.
Eisai is also conducting a Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, and lecanemab is being used as the backbone anti-amyloid therapy in the Tau NexGen clinical study for Dominantly Inherited AD (DIAD).
