Eisai Announces Completion of Rolling BLA for SQ Autoinjector-Delivered Lecanemab

Update November 1, 2024 : Eisai announced today it had completed the rolling submission of the company's biologics license application (BLA) for lecanemab (Leqembi) subcutaneous autoinjector for weekly maintenance dosing in the treatment of adults with early Alzheimer disease (AD). The FDA granted Fast Track designation for the BLA in May 2024 and, if the agency accepts the application, will set a Prescription Drug User Fee Act action date, Eisai said.

The BLA is based on data from the open label extension of the phase 3 Clarity AD trial (NCT03887455), the pivotal study that led to the FDA approval of lecanemab in January 2023, as well as modeling of observed data. The subcutaneous autoinjector under review delivers a 360 mg weekly maintenance dose of lecanemab in approximately 15 seconds, making administration more convenient than the approved intravenous (IV) formulation. Use of the autoinjector, either in the home or at a medical facility, will reduce the need for hospital infusion site visits and for nursing care, as well.

The autoinjector maintenance regimen under review would follow completion of the biweekly IV initiation phase of lecanemab, the weekly subcutaneous doses maintaining effective drug concentrations to sustain the clearance of highly toxic protofibrils. Protofibrils are a transient intermediate stage in the process of amyloidβ (Aβ) aggregation and can cause persistent neuronal damage even after Aβ plaque has been cleared from the brain, according to Eisai.

Lecanemab (100 mg/mL injection for intravenous use) is indicated for the treatment of AD. Treatment should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.

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May 16, 2024. A new formulation of lecanemab (Leqembi; Eisai), an FDA-approved therapy for early-stage Alzheimer disease (AD), may be on the way, according to manufacturer Eisai.

In an announcement May 15, the company said it initiated a rolling submission of a biologics license application (BLA) to the FDA for a weekly subcutaneous autoinjector version of the drug for maintenance dosing, which offers administration of the therapy at home or at medical facilities. The FDA had previously granted Fast Track designation for the new formulation, according to Eisai.

The BLA is based on data from the open label extension (OLE) of the phase 3 Clarity AD trial (NCT03887455), the supportive study that led to the FDA approval of lecanemab in January 2023, as well as modeling of observed data. The subcutaneous autoinjector under review delivers a 360 mg weekly maintenance dose of lecanemab in less time and more conveniently than the originally approved intravenous (IV) formulation, reducing the need for hospital visits and nursing care.

The autoinjector maintenance regimen under review would follow completion of the biweekly IV initiation phase of lecanemab, the weekly subcutaneous doses maintaining effective drug concentrations to sustain the clearance of highly toxic protofibrils.

The promise of subcutaneous lecanemab dosing was on display at the 2023 Clinical Trials on Alzheimer’s Disease (CTAD) Conference, where data on treatment with this new formulation showed 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% increase in amyloid plaque removal with subcutaneous vs 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 via subcutaneous administration 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

Update November 1, 2024

Eisai completes rolling submission to US FDA for Lequembi (lecanemab-irmb) biologics license application for subcutaneous maintenance dosing for the treatment of early Alzheimer’s Disease under the fast track status. News release. Eisai. November 1, 2024. Accessed November 1, 2024. https://www.eisai.com/news/2024/news202482.html

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. Eisai. 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.