Eisai Commences Rolling BLA for Subcutaneous Autoinjector Form of Lecanemab

Reisa Sperling, MD

A new formulation of lecanemab (Leqembi; Eisai), an FDA-approved therapy for early-stage Alzheimer disease (AD), may be on the way, according to Eisai, the drug manufacturers of the agent. In a new announcement, the company noted it initiated a rolling submission of a biologics license application (BLA) to the FDA for a subcutaneous autoinjector version of the drug for maintenance dosing, allowing easy administration of the therapy at home or at medical facilities.

The BLA is based on data from the phase 3 Clarity AD trial (NCT03887455), otherwise known as the supportive trial that led to lecanemab’s approval, its open-label extension (OLE), and modeling of observed data. The subcutaneous autoinjector under review delivers 360 mg weekly maintenance dosing of lecanemab that takes less time than the intravenous (IV) formulation, the formulation it was originally approved in. It is intended to facilitate easier treatment of the drug, thus reducing the need for hospital visits and nursing care.

Earlier this year, prior to the BLA submission, the FDA claimed it would not approve the subcutaneous formulation of lecanemab unless it gained fast track designation specific to the subcutaneous dosing. Months later, the therapy gained fast track designation for the subcutaneous formulation, thus meeting the FDA’s needs. In the new BLA submission, patients who have completed the biweekly IV initiation phase of lecanemab are still eligible to receive weekly doses that maintain effective drug concentrations to sustain the clearance of highly toxic protofibrils.

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The promise of subcutaneous lecanemab dosing was on display at the 2023 Clinical Trials on Alzheimer’s Disease (CTAD) Conference, where treatment with this new formulation resulted in greater amyloid plaque removal than biweekly IV administration. In a preliminary 6-month analysis of the Clarity AD OLE, data from a subgroup of patients showed a 14% increased amyloid plaque removal with the subcutaneous method than IV administration. Pharmacokinetic data also revealed that 90% exposure for subcutaneous vs IV was within the bioequivalence limits of 80% to 125%, allowing Eisai to select a dose for future patients that achieve area under the curve (AUC) that are comparable to the IV formulation dose.

The analysis, led by Reisa Sperling, MD, a neurologist at Brigham and Women’s Hospital, Harvard Medical School, included 72 patients with early AD who received lecanemab for the first time in a subcutaneous way and 322 patients who received IV lecanemab in the Clarity AD core study followed by subcutaneous administration in the substudy. After 6 months, investigators observed reductions of –40.3 (±2.27) centiloids for newly treated patients on subcutaneous lecanemab vs reductions of –35.4 (±1.14) centiloids for those on IV administration. In addition, the weekly subcutaneous pharmacokinetic AUC were 11% higher than the biweekly IV formulation.

In the Clarity AD core study, 12.6%, 17.3%, and 8.9% of patients reported ARIA-edema, ARIA-H (cerebral microhemorrhage because of ARIA, cerebral hemorrhage, and brain surface hemosiderin deposition) and ARIA-H alone, respectively, with intravenous lecanemab. Among the subgroup of 72 patients on subcutaneous lecanemab in the new analysis, investigators observed incidence rates of 16.7%, 22.2%, and 8.3%, respectively; however, Eisai noted that no exact comparison was made because of the sample size of individuals.

REFERENCES
1. Eisai Initiates Rolling Biologics License Application to US FDA for LEQEMBI® (lecanemab-irmb) for Subcutaneous Maintenance Dosing for the Treatment of Early Alzheimer’s Disease Under the Fast Track Status. News release. May 15, 2024. Accessed May 15, 2024. https://www.eisai.com/news/2024/news202430.html
2. Irizarry M, Li D, Dhadda S, Hersch S, Reyderman L, Kramer L. Preliminary update on lecanemab safety in Clarity AD open-label extension, including subcutaneous formulation. Presented at: CTAD conference; October 24-27, 2023; Presentation 4.