FDA Approves New IV Maintenance Dosing for Alzheimer Treatment Lecanemab

According to an announcement from Eisai, the FDA has approved the company’s intravenous (IV) maintenance dosing for lecanemab-irmb, an antiamyloid medication for patients with early-stage Alzheimer disease (AD). As part of the approval, patients completing biweekly IV initiation would receive IV doses once every 4 weeks to maintain effective clearance of toxic protofibrils, thus preventing neuronal injury.¹

The supplemental biologics license application (sBLA) for the latest IV maintenance dosing 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. For context, lecanemab was originally approved under accelerated approval pathway using Study 201, and was later granted traditional approval in July 2023 based on data from Study 301, the confirmatory trial.²

Originally approved as a 100 mg/mL injection for patients with mild cognitive impairment (MCI) or mild dementia stages of the disease, lecanemab’s new once-monthly dosing regimen is believed to be less burdensome and easier for patients while maintaining clinical and biomarker benefits. The sBLA submission for this new maintenance dosing was submitted in April 2024, with the FDA accepting it for review less than 3 months later.

Lecanemab, a monoclonal antibody designed to target and clear amyloid-ß protofibrils, was the second antiamyloid treatment to reach market, behind Biogen’s aducanumab, which was removed in early 2024. By binding to these protofibrils, lecanemab helps to reduce amyloid-ß deposits, aiming to slow cognitive decline and other symptoms of AD. This mechanism focuses on addressing one of the underlying pathologies of the disease rather than just managing its symptoms.

READ MORE: FDA Accepts BLA for Subcutaneous Autoinjector Formulation of Lecanemab

In its clinical development, Clarity AD served as a pivotal trial that ultimately led to lecanemab’s traditional approval. Featuring 1795 patients with early-stage AD, results from the study showed that lecanemab met its primary end point of change in Clinical Dementia Rating-Sum of Boxes (CDR-SB) score, with treated patients demonstrating a statistically significant 27% reduction. Published in the New England Journal of Medicine, the study also met secondary end points of change in amyloid PET centiloids (difference in least squares [LS], –50.12; P <.0001) and Alzheimer’s Disease Assessment Scale-Cognitive 14 (LS difference, –1.442; P = .00005) relative to placebo over the 18-month period.³

Lecanemab comes with a boxed warning and is contraindicated for patients with serious hypersensitivity to lecanemab-irmb or to any of its inactive ingredients. The prescribing information states that testing for apolipoprotein e4 status should be performed before starting treatment with lecanemab to inform the risk of developing amyloid-related imaging abnormalities (ARIA).

In Clarity AD, symptomatic ARIA occurred in 3% (29 of 898) of patients treated with lecanemab, with serious symptoms reported in 0.7% (6 of 898). Clinical symptoms of ARIA resolved in 79% (23/29) of cases during observation. Overall, ARIA, including asymptomatic radiographic events, was observed in 21% (191/898) of lecanemab-treated patients compared to 9% (84/897) with placebo. Specifically, ARIA-E occurred in 13% (113/898) of lecanemab patients versus 2% (15/897) on placebo, while ARIA-H was seen in 17% (152/898) versus 9% (80/897) on placebo. Importantly, there was no increase in isolated ARIA-H in the lecanemab group compared to placebo.

At the 2024 Alzheimer’s Association International Conference, 3-year data from the OLE of Clarity AD continued to highlight lecanemab’s effect on patients living with AD. Over 3 years of treatment across the core study and OLE, lecanemab reduced cognitive decline on CDR-SB by –0.95 compared with the expected decline based on those in the Alzheimer’s Disease Neuroimaging Initiative group. For context, a change of –0.45 (P = .00005) was observed between lecanemab and placebo at the 18-month mark of the core study.⁴

REFERENCES
1. FDA Approves LEQEMBI® (lecanemab-irmb) IV Maintenance Dosing for the Treatment of Early Alzheimer's Disease. News release. Eisai. January 26, 2025. Accessed January 26, 2025. https://media-us.eisai.com/2025-01-26-FDA-Approves-LEQEMBI-R-lecanemab-irmb-IV-Maintenance-Dosing-for-the-Treatment-of-Early-Alzheimers-Disease
2. FDA Converts Novel Alzheimer’s Disease Treatment to Traditional Approval. FDA. News release. July 6, 2023. Accessed January 25, 2025. https://www.fda.gov/news-events/press-announcements/fda-converts-novel-alzheimers-disease-treatment-traditional-approval
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
4. New Clinical Data Demonstrates Three Years of Continuous Treatment with Dual-Acting LEQEMBI® (lecanemab-irmb) Continues to Significantly Benefit Early Alzheimer’s Disease Patients Presented at The Alzheimer’s Association International Conference (AAIC) 2024. News release. Eisai. July 30, 2024. Accessed January 25, 2025. https://www.multivu.com/players/English/9282551-eisai-leqembi-clinical-data-aaic-2024-alzheimers/