Eisai Co., Ltd. and Biogen Inc. have taken a significant step forward in the fight against Alzheimer’s disease by submitting a Supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for LEQEMBI (lecanemab-irmb), proposing a monthly maintenance dosing regimen for patients with early-stage Alzheimer’s. LEQEMBI, initially approved for the treatment of Alzheimer's disease in those with mild cognitive impairment or mild dementia, is at the forefront of efforts to manage this debilitating condition.

This new monthly intravenous (IV) regimen is designed for patients who have already undergone a biweekly IV initiation phase, with the duration of this phase currently under FDA discussion. The aim is to maintain an effective concentration of the drug, facilitating the continuous clearance of toxic protofibrils* associated with neuronal injury even after amyloid-beta (Aβ) plaque clearance.

The submission is bolstered by data from a comprehensive study regime, including the Phase 2 study (Study 201) and its open-label extension (OLE), along with the Clarity AD study (Study 301) and its OLE. These studies underline the drug’s potential in maintaining cognitive function by targeting protofibrils, believed to be a key driver of Alzheimer’s progression.

Eisai also addressed its strategy for a Biologics License Application (BLA) for a weekly subcutaneous (SC) maintenance dose of lecanemab. Initially planned for March 2024, the process hit a regulatory speed bump requiring additional immunogenicity data. The FDA has indicated that a separate Fast Track designation for the SC formulation is necessary for a rolling review, prompting Eisai to request this designation with the hope of initiating a rolling submission.

Alzheimer's disease represents a continuous neurotoxic challenge, with early intervention seen as crucial to slowing its progression. The maintenance dosing regimen of LEQEMBI seeks not only to halt disease advancement but to offer a more manageable treatment option for patients and caregivers, reflecting the urgent need for effective early-stage Alzheimer’s therapies.

LEQEMBI’s approval and application status spans globally, with Eisai leading its development and regulatory submissions in partnership with Biogen. The drug is currently approved in the U.S., Japan, and China, with applications pending in numerous other jurisdictions.

Alzheimer's disease, characterized by the accumulation of Aβ plaques and neurofibrillary tangles, leads to progressive cognitive decline. The targeting of protofibrils in treatment strategies represents a novel approach in mitigating the impact of Alzheimer's, emphasizing the importance of maintaining neuronal health and cognitive function.

*Protofibrils, a particularly toxic form of Aβ, play a pivotal role in the cognitive deterioration seen in Alzheimer’s disease, damaging neurons and disrupting critical neural connections. The reduction of protofibrils is a key focus in the development of treatments aiming to preserve cognitive abilities in Alzheimer's patients.