UPDATE 6-11-2024: Eisai Files sBLA for Lecanemab-irmb Maintenance Dosing

Update June 11, 2024. Eisai announced yesterday acceptance by the FDA of the company's supplemental biologics license application (sBLA) for monthly IV maintenance dosing of lecanemab (lequembi). The agency has set a Prescription Drug User Fee Act action date for January 25, 2025.

In addition, Eisai initiated a rolling submission to the FDA for the lecanemab subcutaneous autoinjector for weekly maintenance dosing after receiving fast track designation from the FDA in May.

Eisai has submitted a supplemental biologics license application (sBLA) to the US Food and Drug Administration (FDA) to extend the label for its Alzheimer disease (AD) therapy lecanemab-irmb (Leqembi) to include a maintenance dosing regimen that would reduce the number of intravenous infusions needed to one per month, according to an April 1 announcement.

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For individuals who have completed the treatment’s induction phase of biweekly infusions, the exact duration of which is under discussion with the FDA, the maintenance regimen would call for a monthly IV dose to maintain a concentration of lecanemab that would sustain clearance of highly toxic precursors to the amyloid beta plaque that induction treatment has cleared from the brain, said Eisai. These so called “protofibrils” can continue to damage neurons even after the plaque has been removed.

Leqembi is currently approved by the FDA for the treatment of adults with AD who have mild cognitive impairment or mild dementia, a stage of the progressive disease referred to as “early AD,” but there have been questions about a continued benefit from staying on treatment in a maintenance phase.

Submission of the sBLA is part of an ongoing development plan that also included initiating a rolling SBA in March for a once-weekly maintenance regimen administered subcutaneously. The company also announced today, however, that it will not be able to submit the application under the existing fast-track and breakthrough designations for lecanemab. The FDA has notified Eisai and development partner Biogen that the rolling review requires a specific fast-track designation for the SC formulation, according to Eisai.

In the April 1 announcement Eisai and Biogen said a fast-track application has now been filed and initiates a review period of up to 60 days. If approved, the companies will launch the rolling BLA.

The current sBLA filing for the monthly IV dosing may yet provide a maintenance option for eligible individuals. The filing is based on modeling data from the companies’ phase 2 study (Study 201) and its open-label extension as well as the phase 3 Clarity AD study and its OLE. Results of analysis of 24-month data from these clinical trials suggests a benefit to continued treatment with lecanemab after clearance of amyloid plaques, according to the announcement.

"Studies have suggested that amyloid plaques start to reaccumulate after treatment with anti-amyloid stops – estimates are by around 3% to 4% per year – according to Biogen’s head of development Priya Singhal" who was quoted by pharmaphorum speaking during a previous analyst call. “'Biomarkers…reflecting disease progression continue to accumulate as soon as patients are off drug.' She added: 'Evidence points us to the fact that…continuing drug to some level is going to be important' while acknowledging that questions still remain about the frequency and duration of maintenance."

Leqembi is now approved in the US, Japan, and China, and is under regulatory review in Europe and other markets.

Source: Eisai completes submission of LEQEMBI (lecanemab-irmb) supplemental biologics license application for IV maintenance dosing for the treatment of early Alzheimer's disease to the US FDA. Eisai. News release. April 1, 2024. Accessed April 1, 2024. https://www.eisai.com/news/2024/news202423.html