Eisai Co., Ltd. and Biogen Inc. announced the completion of a rolling submission to the U.S. Food and Drug Administration (FDA) for lecanemab-irmb (LEQEMBI®) subcutaneous autoinjector. This new formulation is intended for weekly maintenance dosing in patients with Mild Cognitive Impairment (MCI) or mild dementia stage of Alzheimer's disease (AD), collectively referred to as early AD.
The FDA had previously granted Fast Track designation to this application. If accepted, the Prescription Drug User Fee Act (PDUFA) action date will be set, marking a significant step toward potential approval.
The Biologics License Application (BLA) is based on data derived from the Clarity AD (Study 301) open-label extension (OLE) and modeling of observed data. The subcutaneous autoinjector is designed for ease of use, allowing patients or caregivers to administer the drug at home or in medical facilities, with an injection process estimated to take approximately 15 seconds.
Clinical Rationale for Subcutaneous Maintenance Dosing
The subcutaneous autoinjector delivers a 360 mg weekly maintenance regimen. Patients who have completed the biweekly intravenous (IV) initiation phase would transition to these weekly doses. This approach aims to maintain effective drug concentrations, sustaining the clearance of highly toxic protofibrils, which are considered a primary driver of neuronal injury even after amyloid-beta (Aβ) plaques have been cleared from the brain.
Data suggest that early and continuous treatment may prolong the therapeutic benefits, even after plaque removal. Eisai anticipates that the subcutaneous formulation will be more convenient for patients and their care partners, reducing the burden of hospital or infusion site visits and potentially lessening the need for extensive nursing care compared to IV administration.
Regulatory Landscape and Global Approvals
LEQEMBI is currently approved 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 (EU). The FDA accepted Eisai's Supplemental Biologics License Application (sBLA) for monthly LEQEMBI IV maintenance dosing in June 2024, with a PDUFA action date set for January 25, 2025.
Eisai leads the development and regulatory submissions for lecanemab globally, with Eisai and Biogen co-commercializing and co-promoting the product. Eisai retains final decision-making authority.
Safety Information and Warnings
LEQEMBI carries a boxed warning for Amyloid-Related Imaging Abnormalities (ARIA), including ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H). Patients who are Apolipoprotein E ε4 (ApoE ε4) homozygotes have a higher incidence of ARIA. Testing for ApoE ε4 status should be performed prior to treatment initiation.
Other warnings and precautions include hypersensitivity reactions and infusion-related reactions (IRRs). Common adverse reactions include IRRs, ARIA-H, ARIA-E, headache, superficial siderosis of the central nervous system, rash, and nausea/vomiting.
