Eisai Co., Ltd. has announced the completion of its rolling submission to the U.S. Food and Drug Administration (FDA) for the Biologics License Application (BLA) of LEQEMBI® (lecanemab-irmb) for subcutaneous maintenance dosing in patients with Alzheimer's disease (AD). This submission aims to secure approval for a subcutaneous autoinjector that would allow weekly administration of LEQEMBI® at home or in medical facilities, offering a more convenient alternative to bi-weekly intravenous (IV) infusions. The injection process is expected to take approximately 15 seconds.
The BLA is based on data from the Clarity AD (Study 301) open-label extension (OLE) and modeling of observed data. The subcutaneous autoinjector is designed to deliver a 360 mg weekly maintenance regimen, ensuring patients who have completed the IV initiation phase receive consistent doses. This approach seeks to maintain effective drug concentrations necessary to sustain the clearance of highly toxic protofibrils, which are considered a primary driver of neuronal injury even after amyloid-beta (Aβ) plaques have been cleared from the brain.
Clinical Significance of Subcutaneous Administration
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 offers a more patient-friendly method of drug delivery, potentially reducing the need for frequent hospital or infusion site visits and minimizing the burden on nursing care. Eisai anticipates that this new administration route will enhance patient convenience and adherence to treatment.
LEQEMBI®: Mechanism and Clinical Data
LEQEMBI® is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody that targets aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). It is currently approved in the U.S., Japan, China, South Korea, Hong Kong, Israel, the United Arab Emirates, and Great Britain for the treatment of Alzheimer's disease in patients with mild cognitive impairment (MCI) or mild dementia. Approvals were based on Phase 3 data from the Clarity AD clinical trial, which demonstrated statistically significant results in meeting its primary endpoint and all key secondary endpoints.
In the Clarity AD trial, lecanemab reduced clinical decline on the Clinical Dementia Rating Sum of Boxes (CDR-SB) by 27% at 18 months compared to placebo (difference, -0.45; 95% CI, -0.67 to -0.23; P<0.001). Additionally, the Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL) showed a statistically significant benefit of 37% compared to placebo (difference, 2.0; 95% CI, 1.2 to 2.8; P<0.001).
Safety Considerations
LEQEMBI® carries a boxed warning for Amyloid-Related Imaging Abnormalities (ARIA), which includes ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H). Patients who are Apolipoprotein E ε4 (ApoE ε4) homozygotes have a higher incidence of ARIA. Monitoring with MRI is recommended, especially during the initial phase of treatment. Other common adverse reactions include infusion-related reactions (IRRs), headache, and superficial siderosis of the central nervous system.
Collaboration and Future Directions
Eisai serves as the lead for lecanemab's development and regulatory submissions globally, with Eisai and Biogen co-commercializing and co-promoting the product. Eisai retains final decision-making authority. Ongoing clinical studies, such as the AHEAD 3-45 trial for individuals with preclinical AD and the Tau NexGen clinical study for Dominantly Inherited AD (DIAD), continue to explore the potential of lecanemab in earlier stages of the disease.
