Eisai Co., Ltd. and Biogen Inc. 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 (early AD) who have completed the biweekly intravenous (IV) initiation phase. The FDA had previously granted Fast Track designation to this application.
The BLA is based on data derived from the Clarity AD (Study 301) open-label extension (OLE) and modeling of observed data. The subcutaneous autoinjector is designed for ease of use, potentially allowing patients or caregivers to administer LEQEMBI® at home or in medical facilities, with an injection process expected to take approximately 15 seconds.
Clinical Significance of Subcutaneous Lecanemab
The shift to subcutaneous administration aims to maintain effective drug concentrations, sustaining the clearance of highly toxic protofibrils—a form of amyloid-beta (Aβ) believed to contribute significantly to neuronal injury even after amyloid plaque removal. Data suggest that early and continuous treatment may prolong the benefits of therapy, even after plaque clearance.
According to Eisai, the subcutaneous autoinjector is expected to be more convenient for patients and their care partners and may reduce the need for hospital or infusion site visits and nursing care compared to IV administration. This aligns with the understanding that Alzheimer's disease involves an ongoing neurotoxic process that begins before and continues after plaque deposition.
Regulatory Landscape and Global Approvals
LEQEMBI® has already secured approvals in the U.S., Japan, China, South Korea, Hong Kong, Israel, UAE, and Great Britain. Eisai has also submitted applications for approval of lecanemab in 10 countries and regions, including the European Union (EU). The US FDA accepted Eisai’s Supplemental Biologics License Application (sBLA) for monthly LEQEMBI IV maintenance dosing in June 2024 and set a PDUFA action date for January 25, 2025.
Lecanemab's Mechanism and Clinical Trial Data
Lecanemab is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody that targets aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). The drug's approval in various regions was based on Phase 3 data from the Clarity AD clinical trial, which 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 the Clinical Dementia Rating-Sum of Boxes (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). 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 Information
LEQEMBI carries a boxed warning for Amyloid-Related Imaging Abnormalities (ARIA), which can manifest as 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, and caution should be exercised in patients with risk factors for intracerebral hemorrhage or those on anticoagulant therapy.
Infusion-related reactions (IRRs) have also been observed, with most cases being mild to moderate in severity. Symptoms of IRRs include fever, flu-like symptoms, nausea, vomiting, hypotension, hypertension, and oxygen desaturation.
