FDA Accepts Eisai’s sBLA for New IV Maintenance Dosing of Lecanemab

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If the sBLA is approved, the clinical and biomarker benefits may be maintained through the once-monthly dosing regimen that is less burdensome and easier for patients and care partners to continue long-term.

Slightly more than 2 months after it was submitted, the FDA has accepted Eisai’s supplemental biologics license application (sBLA) for a new monthly intravenous (IV) maintenance dosing of lecanemab-irmb (Leqembi), its approved medication for early-stage Alzheimer disease (AD). As a result, the agency has set a PDUFA action date for January 25, 2025, to give a final answer.¹

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. In addition, Eisai noted that it has initiated a rolling submission of a BLA to the FDA for a subcutaneous autoinjector version of lecanemab that allows maintenance dosing of the antiamyloid therapy. For context, the autoinjector gained fast track designation by the agency earlier this year in May.²

Lecanemab, which gained traditional approval in July 2023, was greenlit as a 100 mg/mL injection for patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. The newly accepted sBLA was based on modeling of observed data from the phase 2 study (Study 201; NCT01767311) and its open-label extension (OLE), as well as the phase 3 Clarity AD trial (Study 301; NCT03887455), and its OLE study. Lecanemab originally was approved under accelerated approval pathway using Study 201, and was later granted traditional approval based on data from Study 301, the confirmatory trial.

Formerly known as BAN2401, lecanemab is a humanized monoclonal antibody that eliminates toxic amyloid-ß protofibrils. Clarity AD, published in the New England Journal of Medicine, included 1795 patients with evidence of amyloid on PET or cerebrospinal fluid who were followed around for an 18-month treatment period. At the conclusion of the analysis, lecanemab met its primary end point of change in Clinical Dementia Rating-Sum of Boxes score, with treated patients demonstrating a statistically significant 27% reduction.³

The approval of lecanemab was the second antiamyloid agent of its class, following Biogen’s aducanumab (Aduhelm) in 2021. Aducanumab no longer is on the market following the company’s decision earlier this year to withdraw it and allocate resources to other therapeutic programs, including lecanemab. Eli Lilly’s investigational agent donanemab looks to be the next therapy to join the class, with a potential decision expected to come in the next few months.

Lecanemab remains contraindicated in patients with serious hypersensitivity to the therapy or any of the excipients of lecanemab. There are several labeled warnings and precautions to the treatment, including amyloid-related imaging abnormalities, hypersensitivity reactions, and adverse reactions. It remains approved in other countries such as China, Japan, and South Korea, while still seeking approval in 13 other countries and regions, including the European Union.

REFERENCES
1. 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 June 10, 2024. 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
2. Eisai Initiates Rolling Biologics License Application to US FDA for LEQEMBI® (lecanemab-irmb) for Subcutaneous Maintenance Dosing for the Treatment of Early Alzheimer’s Disease Under the Fast Track Status. News release. May 15, 2024. Accessed June 10, 2024. https://www.eisai.com/news/2024/news202430.html
3. van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388:9-21. doi:10.1056/NEJMoa2212948