The FDA Accepts Eisai BLA for Lecanemab Subcutaneous Maintenance Dosing in Adults with Alzheimer Disease

The FDA has accepted the Biologics License Application (BLA) from Eisai for lecanemab-irmb (Lequembi) in a subcutaneous autoinjector (SC-AI) form for weekly maintenance dosing. If approved, LEQEMBI will become the only FDA-approved anti-amyloid therapy for Alzheimer’s disease (AD) provided in this form, Eisai stated in a company news release.1

The autoinjector can be used for lecanemab administration at home or at medical facilities and was granted Fast Track designation in June 2024. The FDA has set a Prescription Drug User Fee Act (PDUFA) action date for August 31, 2025.1

The announcement comes as the FDA works toward a PDUFA date of January 25, 2025, to decide on approval of monthly IV maintenance dosing of lecanemab.

Lecanemab is indicated for the treatment of AD in patients with mild cognitive impairment (MCI) or mild dementia stages, collectively referred to as early AD. The SC-AI submission is supported by data from the phase 3 Clarity AD (Study 301) open-label extension (OLE) study and predictive modeling of observed data.2 Findings from Clarity AD served as the foundation for the original FDA approval of lecanemab in January 2023. This new administration method could simplify treatment by allowing patients to receive 360-mg weekly maintenance doses at home following the biweekly intravenous (IV) initiation phase. The treatment continuation is expected to maintain clinical and biomarker benefits reached during that phase.

The subcutaneous injection process is designed to be straightforward, requiring approximately 15 seconds per administration.

Supporting Data

Eisai first shared the promise of SC-AI administration of lecanemab at the 2023 Clinical Trials on Alzheimer’s Disease (CTAD) Conference, where data on treatment using the new format 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.2 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.2

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.2

AD is a progressive neurodegenerative disease driven by toxic amyloid-beta (Aβ) protofibrils and plaques. Lecanemab uniquely addresses AD pathophysiology by targeting 2 key processes: clearing highly toxic Aβ protofibrils and rapidly reducing Aβ plaque. Protofibrils are neurotoxic and may continue to damage neurons even after plaque clearance. Data from the 3-year Clarity AD study, presented at the Alzheimer’s Association International Conference (AAIC) in 2024, suggest that early and sustained treatment with lecanemab may prolong therapeutic benefits by mitigating neuronal injury over the long term, according to Eisai.

The SC-AI form of lecanemab offers significant logistical and clinical advantages. By reducing the need for infusion site visits and nursing care associated with IV administration, the subcutaneous option simplifies maintenance therapy, potentially increasing adherence and accessibility for patients and caregivers. Use of the SC-AI could be particularly impactful given the progressive and relentless nature of AD, which places a substantial burden on healthcare systems and families.

Lecanemab is approved for use in multiple countries, including the United States, Japan, China, South Korea, and the United Kingdom, among others. In November 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion recommending approval in the European Union. Eisai has also filed regulatory applications for lecanemab in 17 additional countries and regions.

References

FDA Accepts LEQEMBI® (lecanemab-irmb) Biologics License Application for Subcutaneous Maintenance Dosing for the Treatment of Early Alzheimer's Disease. News release. Eisai. January 14, 2025. Accessed January 14, 2025. https://www.eisai.com/news/2025/news202502.html

Halsey G. Eisai announces completion of rolling BLA for SC autoinjector-delivered lecanemab. Patient Care. November 1, 2024. https://www.patientcareonline.com/view/eisai-announces-submission-of-rolling-bla-for-sq-autoinjector-delivered-lecanemab

van Dyck C, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer's disease. N Engl J Med. 2023;388:9-21. https://www.nejm.org/doi/full/10.1056/NEJMoa2212948