Eisai Co., Ltd. and Biogen Inc. have announced the completion of a rolling submission to the U.S. Food and Drug Administration (FDA) for a Biologics License Application (BLA) concerning LEQEMBI® (lecanemab-irmb). This submission pertains to a subcutaneous autoinjector formulation designed for weekly maintenance dosing, following an initial intravenous (IV) treatment phase. The FDA had previously granted Fast Track designation to this application.
The intended use of LEQEMBI is for the treatment of Alzheimer’s disease (AD) in patients experiencing Mild Cognitive Impairment (MCI) or those in the early stages of dementia. If the FDA accepts the BLA, a Prescription Drug User Fee Act (PDUFA) action date will be established, setting a target date for the completion of the review process.
Clinical Data and Rationale
The BLA is underpinned by 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, potentially allowing patients to self-administer LEQEMBI at home or in medical facilities, with an estimated injection time of approximately 15 seconds. The weekly 360 mg subcutaneous maintenance regimen is intended to maintain effective drug concentrations, sustaining the clearance of neurotoxic protofibrils, which are implicated in ongoing neuronal injury even after amyloid-beta (Aβ) plaque removal from the brain.
Addressing Alzheimer's Progression
Alzheimer’s disease is characterized by a continuous neurotoxic process that initiates before and persists after plaque deposition. Evidence suggests that early and continuous treatment may extend the therapeutic benefits, even after plaque clearance. The subcutaneous autoinjector aims to provide a more convenient administration method for patients and their caregivers, potentially reducing the reliance on hospital or infusion site visits and minimizing the need for extensive nursing care compared to IV administration.
Global Approvals and Submissions
LEQEMBI has already secured approvals in the U.S., Japan, China, South Korea, Hong Kong, Israel, UAE, and Great Britain. Eisai has also submitted applications for approval in 10 additional 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.
Collaboration and Commercialization
Eisai is the lead entity for the development and regulatory submissions of lecanemab globally. Eisai and Biogen co-commercialize and co-promote the product, with Eisai retaining final decision-making authority.
Targeting Protofibrils
Protofibrils are considered a highly toxic form of Aβ, believed to significantly contribute to the neuronal injury associated with AD and cognitive decline. They can damage brain cell membranes and disrupt nerve signal transmission. Reducing protofibrils may prevent AD progression by mitigating neuronal damage and cognitive dysfunction.
Clarity AD Trial Results
LEQEMBI’s approvals are based on Phase 3 data from the global Clarity AD clinical trial, which met its primary endpoint and all key secondary endpoints with statistically significant results. Lecanemab reduced clinical decline on the Clinical Dementia Rating Sum of Boxes (CDR-SB) by 27% at 18 months compared to placebo (P<0.001). The AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL) also showed a statistically significant benefit of 37% compared to placebo (P<0.001).
