Eisai seeks FDA approval of Leqembi IV maintenance dosing

Proposal for patients to get monthly IV dose after twice monthly initiation

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by Andrea Lobo |

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Eisai is seeking approval in the U.S. of Leqembi (lecanemab)’s monthly maintenance dosing for people with early Alzheimer’s disease.

The supplemental biologics license application with the U.S. Food and Drug Administration (FDA), recently announced by the company, is backed by modeling of observed data from the Phase 2b Study 201 clinical trial (NCT01767311), the confirmatory Phase 3 Clarity AD trial (NCT03887455), and their open-label extension portions.

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Trial data: Cognitive decline slowed in patients after 1.5 years on Leqembi

Previous data from these studies had shown the therapy, given twice monthly, significantly eased amyloid-beta accumulation in the brain, and slowed cognitive decline after 1.5 years. Some patients in Study 201 received the therapy once monthly.

These findings supported the therapy’s conditional approval and subsequent full approval in the U.S., when given as an intravenous (into-the-vein) infusion at a dose of 10 mg/kg of body weight, once every two weeks.

As part of the proposed regimen, patients who have completed the twice monthly initiation phase — the period under discussion with the FDA — would receive a monthly intravenous dose to maintain effective drug concentration to sustain clearance of amyloid beta toxic clumps.

Alzheimer’s is characterized by the accumulation of toxic protein clumps (plaques), particularly of amyloid beta and tau, inside the brain’s nerve cells, or neurons, which are thought to play a key role in driving the disease.

Leqembi, being co-developed by Eisai and Biogen, is an antibody-based therapy designed to target the most neurotoxic form of amyloid beta called protofibrils, subsequently promoting their clearance. Therefore, the therapy is thought to slow disease progression in people with early-stage Alzheimer’s and evidence of amyloid beta buildup in the brain.

However, even after these plaques have been cleared from the brain, protofibrils can continue to cause neuronal damage. Continued maintenance dosing is intended to maintain the clinical and biomarker benefits, using a dosing regimen that may be more convenient for patients and their caregivers.

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Eisai seeking FDA fast-track status for subcutaneous formulation of Leqembi

Eisai also submitted a request in March for fast-track designation for the under-the-skin, or subcutaneous, formulation of Leqembi. This status is meant to help experimental therapies with the potential to fill unmet medical needs get to market faster.

It also allows a rolling submission, in which companies can submit individual sections of the application for review by the FDA as soon as they are completed, rather than waiting to file the entire document at once, as is typical.

Should the agency grant fast-track designation to the subcutaneous formulation — a decision which is expected in the next months — Eisai plans to initiate a rolling submission seeking the approval of that formulation as a weekly maintenance treatment.

The planned regulatory filing will be based on positive intermediate results from a sub-study of the Clarity AD trial’s open-label extension portion, in which patients were either switched from Leqembi to the subcutaneous formulation or started lecanemab treatment already with the experimental formulation.

Data demonstrated that six months of weekly dosing of the subcutaneous formulation, at a dose of 720 mg, was superior to the approved every-other-week intravenous infusions of Leqembi at removing amyloid beta clumps from patients’ brains.

Leqembi is also approved in Japan and China, and regulatory applications have been submitted in several other regions and countries, including Canada, the European Union, and Great Britain.