Submission of Leqembi (lecanemab-irmb) supplemental biologics license application for IV maintenance dosing for the treatment of early Alzheimer’s disease to the FDA

Leqembi is indicated for the treatment of Alzheimer’s disease (AD) in patients with mild cognitive impairment or mild dementia stage of disease (collectively referred to as early AD).

As part of the monthly IV maintenance regimen, patients who have completed the biweekly IV initiation phase, exact period under discussion with the FDA, would receive a monthly IV dose that maintains effective drug concentration to sustain the clearance of highly toxic protofibrils which can continue to cause neuronal injury even after the amyloid-beta (Alpha beta) plaque has been cleared from the brain. The sBLA is based on modeling of observed data from the Phase II study (Study 201) and its ITS open-label extension (OLE) as well as Clarity AD study (Study 301)and its OLE.

Eisai had aimed to submit a Biologics License Application (BLA) for weekly maintenance therapy using subcutaneous (SC) administration in March 2024. To respond to the FDA’s recent requirement of additional three-month immunogenicity data at the proposed maintenance dose of 360 mg weekly, Eisai planned to initiate a rolling BLA for lecanemab SC maintenance in March 2024, under the existing Fast Track and Breakthrough Therapy designations. However, Eisai was recently informed by the FDA that a Fast Track designation specific for the SC formulation is needed to receive rolling review. Following the guidance, Eisai submitted a request for Fast Track designation for the SC formulation and will initiate a rolling submission should the FDA grant this designation. The Fast Track designation will be determined within 60 days from the March 2024 submission.

AD is an ongoing neurotoxic process that begins before and continues after plaque deposition. There is an urgency to treat early AD because early and ongoing treatment can slow the progression of AD and continuing treatment may prolong the benefit even after plaque is cleared from the brain. The earlier Mild Cognitive Impairment (MCI) due to AD and mild AD dementia are diagnosed and treated, the greater the opportunity for the patient to benefit. Continued maintenance dosing is intended to maintain the clinical and biomarker benefits with a dosing regimen that may be more convenient for some patients and their care partners.

Leqembi is now approved in the U.S., Japan and China, and has been submitted for review in the European Union, Australia, Brazil, Canada, Hong Kong, Great Britain, India, Israel, Russia, Saudi Arabia, South Korea, Taiwan, Singapore, and Switzerland. Eisai serves as the lead for lecanemab’s development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.

Protofibrils are believed to contribute to the brain injury that occurs with AD and are considered to be the most toxic form of Alpha beta, having a primary role in the cognitive decline associated with this progressive, debilitating condition. Protofibrils cause injury to neurons in the brain, which in turn, can negatively impact cognitive function via multiple mechanisms, not only increasing the development of insoluble Alpha beta plaques but also increasing direct damage to brain cell membranes and the connections that transmit signals between nerve cells or nerve cells and other cells. It is believed the reduction of protofibrils may prevent the progression of AD by reducing damage to neurons in the brain and cognitive dysfunction.