Eisai Co., Ltd. and Biogen Inc. have announced the completion of a rolling submission to the U.S. Food and Drug Administration (FDA) for a Biologics License Application (BLA) for lecanemab-irmb (LEQEMBI®) subcutaneous autoinjector. This new formulation is intended for weekly maintenance dosing in patients with Mild Cognitive Impairment (MCI) or mild dementia stage Alzheimer's disease (AD), collectively referred to as early AD, and has been granted Fast Track designation by the FDA.
The BLA is supported by data from the Clarity AD (Study 301) open-label extension (OLE) and modeling of observed data. If approved, the LEQEMBI autoinjector would allow for administration at home or in medical facilities, with an injection process expected to take approximately 15 seconds. This subcutaneous option is designed for patients who have completed the biweekly intravenous (IV) initiation phase, providing weekly doses to maintain effective drug concentrations. These concentrations are crucial for sustaining the clearance of highly toxic protofibrils, which can continue to cause neuronal injury even after amyloid-beta (Aβ) plaque has been cleared from the brain.
Clinical Significance of Subcutaneous Lecanemab
Alzheimer's disease is characterized by an ongoing neurotoxic process that begins before and continues after plaque deposition. Data suggest that early and continuous treatment may prolong the benefits of therapy, even after plaques are cleared. The subcutaneous autoinjector is anticipated to be more convenient for patients and their caregivers, potentially reducing the need for frequent hospital or infusion site visits. Eisai and Biogen aim to provide a more manageable treatment experience while maintaining clinical and biomarker benefits.
Global Regulatory Landscape
LEQEMBI is currently approved in the U.S., Japan, China, South Korea, Hong Kong, Israel, UAE, and Great Britain. Eisai has also submitted applications for approval in 10 additional countries and regions, including the European Union (EU). The U.S. FDA accepted Eisai's Supplemental Biologics License Application (sBLA) for monthly LEQEMBI IV maintenance dosing in June 2024, with a Prescription Drug User Fee Act (PDUFA) action date set for January 25, 2025.
Safety and Efficacy Considerations
LEQEMBI's approval is based on Phase 3 data from the global Clarity AD clinical trial, where it met its primary endpoint and all key secondary endpoints with statistically significant results. In the Clarity AD clinical trial, treatment with lecanemab reduced clinical decline on CDR-SB by 27% at 18 months compared to placebo (difference, −0.45; 95% confidence interval [CI], −0.67 to −0.23; P<0.001). The most common adverse events (>10%) in the lecanemab group were infusion reactions and ARIA-H. The adjusted mean change from baseline at 18 months in the ADCS-MCI-ADL score was −3.5 in the lecanemab group and −5.5 in the placebo group (difference, 2.0; 95% CI, 1.2 to 2.8; P<0.001).
Ongoing Research
Eisai and Biogen continue to investigate lecanemab in various clinical settings, including the Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD and the Tau NexGen clinical study for Dominantly Inherited AD (DIAD). These studies aim to further explore the potential of lecanemab in treating and preventing Alzheimer's disease.
