FDA Accepts BLA for Subcutaneous Autoinjector Formulation of Lecanemab

Reisa Sperling, MD

According to a new announcement, the FDA has accepted Eisai’s biologics license application (BLA) for lecanemab-irmb (Leqembi) subcutaneous autoinjector (SC-AI) for weekly maintenance dosing in patients with early-stage Alzheimer disease (AD). The agency has set a PDUFA action date for August 31, 2025, for a decision to be made.¹

If approved by the FDA, lecanemab would become the first AD treatment available for at-home subcutaneous administration using an autoinjector, with injections averaging 15 seconds. Following the biweekly intravenous (IV) initiation phase, patients would transition to weekly 360 mg subcutaneous maintenance doses to sustain clinical and biomarker benefits. Lecanemab, which received traditional approval in July 2023, was originally approved in a 100 mg/mL injection for patients with mild cognitive impairment (MCI) or mild dementia stage of the disease, the population in which treatment was initiated in clinical trials.

The belief is that the new SC-AI will hopefully ease patient care, as well as reduce the need for hospital or infusion site visits and nursing care for IV administration. Data from the pivotal phase 3 Clarity AD trial (NCT03887455)—the study it was originally approved off of—as well as its open-label extension and modeling of observed data, will support the SC-AI’s BLA.

Clarity AD, published in the New England Journal of Medicine, was a large-scale trial that included 1795 patients with evidence of amyloid on PET or cerebrospinal fluid (CSF) who were followed around for an 18-month treatment period. After lecanemab’s approval, a follow-up analysis of the trial was conducted, focusing in on the effects of patients who were treated with subcutaneous lecanemab vs those on biweekly IV lecanemab, the administration route it was approved in.

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The analysis, led by Reisa Sperling, MD, a neurologist at Brigham and Women’s Hospital, Harvard Medical School, showed that after 6 months of treatment, those on the SC-AI demonstrated a 14% increased amyloid plaque removal than those who received IV administration. Pharmacokinetic data also demonstrated 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 that are comparable to the IV formulation dose.²

In total, the analysis comprised of 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. In the Clarity AD study, 12.6%, 17.3%, and 8.9% of patients on intravenous lecanemab experienced ARIA-edema, ARIA-H, and ARIA-H alone, respectively. Among 72 patients on subcutaneous lecanemab, rates were 16.7%, 22.2%, and 8.3%, though direct comparisons were limited by the small sample size.

Since its approval, Eisai has submitted 2 BLAs for lecanemab: one for its SC-AI formulation, as well as another for a new monthly IV maintenance dosing. A decision on the monthly maintenance dosing of lecanemab is expected to come before January 25, 2025, the scheduled PDUFA date. According to the company, those who complete the biweekly IV initiation phase would still receive a monthly IV dose that maintains effective drug concentration to sustain the clearance of highly toxic protofibrils which can continue to cause neuronal injury.³

REFERENCES
1. FDA Accepts LEQEMBI® (lecanemab-irmb) Biologics License Application for Subcutaneous Maintenance Dosing for the Treatment of Early Alzheimer's Disease. News release. Eisai. January 13, 2025. Accessed January 14, 2025. https://www.prnewswire.com/news-releases/fda-accepts-leqembi-lecanemab-irmb-biologics-license-application-for-subcutaneous-maintenance-dosing-for-the-treatment-of-early-alzheimers-disease-302349842.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.
3. FDA Accepts Eisai's Filing of LEQEMBI® (lecanemab-irmb) Supplemental Biologics License Application for IV Maintenance Dosing for the Treatment of Early Alzheimer's Disease. Eisai. June 9, 2024. Accessed January 14, 2025. https://www.prnewswire.com/news-releases/fda-accepts-eisais-filing-of-leqembi-lecanemab-irmb-supplemental-biologics-license-application-for-iv-maintenance-dosing-for-the-treatment-of-early-alzheimers-disease-302167814.html