FDA Accepts Eisai, Biogen’s Biologics License Application for Subcutaneous Leqembi in Early Alzheimer Disease

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The FDA has accepted Biogen and Eisai’s Biologics License Application (BLA) for a subcutaneous (SC) maintenance dosing option of Leqembi (lecanemab-irmb) for early Alzheimer disease (AD). According to the company, the application is supported by data from the Clarity AD open-label extension (OLE) study and modeling of observed results, which demonstrated sustained clinical and biomarker benefits, including the clearance of neurotoxic protofibrils and amyloid-beta plaques.¹

In November 2024, the companies completed a rolling submission to the FDA for the BLA of SC Leqembi. According to Eisai, the goal of the BLA is to enable weekly home or facility-administered SC doses via autoinjector for patients who have finished initial intravenous treatments.

The OLE phase of Clarity AD was a placebo-controlled, double-blind, parallel-group, 18-month study aimed at confirming the safety and efficacy of Leqembi compared to placebo in 1,795 participants with mild cognitive impairment or early-stage AD. The primary endpoint of the study was global cognitive and functional scale based on the Clinical Dementia Rating Sum of Boxes.

Results from the trial demonstrated that Leqembi slowed cognitive and functional decline over 18 months by 27%. Key secondary endpoints demonstrated a notable reduction in amyloid plaque burden at all timepoints from three months onward. Additionally, cognition and daily functioning demonstrated statistically significant improvements.^2,3

Common adverse events included infusion-related reactions (IRRs), amyloid-related imaging abnormalities (ARIA), headache, superficial siderosis of central nervous system, rash, nausea, and vomiting. IRR symptoms included fever and flu-like symptoms, nausea, vomiting, hypotension, hypertension, and oxygen desaturation. While there were deaths in 0.7% and 0.8% of participants in the Leqembi and placebo groups, respectively, none were caused by Leqembi or ARIA.^1-3

According to the Alzheimer’s Association, an estimated seven million people in the United States are currently living with AD, which includes 6.9 million people over 65 years of age, 73% of whom are over 75 years of age. Additional statistics have found that nearly two-thirds of Americans with AD are women. Further, older Black Americans are found to be two times as likely than older whites to have AD or other forms of dementia. Due to an increase in the aging population, the Alzheimer’s Association stated that the number of people with AD could grow to 12.7 million by 2050 unless there is a medical breakthrough.⁴

According to the World Health Organization (WHO), over 55 million people are currently living with some form of dementia, with 60% living in low- and middle-income countries. Other than AD, other forms of dementia include vascular dementia, dementia with Lewy bodies, and multiple diseases that contribute to frontotemporal dementia. WHO states that dementia could also develop as the result of a stroke, in people with HIV, through alcohol abuse, nutritional deficiencies, and continued injuries to the brain. In 2019, dementia cost approximately $1.3 trillion in healthcare costs.⁵

Currently, Leqembi is approved in the United States, Japan, China, South Korea, Hong Kong, Israel, the United Arab Emirates, Great Britain, Mexico, and Macau. Recently, the treatment also received a positive opinion from the Committee for Medicinal Products for Human Use of the European Medicines Agency, while applications for approval are currently pending in 17 other countries and regions. For the current BLA, there is a Prescription Drug User Fee Act target action date of August 31, 2025.¹

References

1. FDA Accepts LEQEMBI® (lecanemab-irmb) Biologics License Application for Subcutaneous Maintenance Dosing for the Treatment of Early Alzheimer’s Disease. Biogen. January 13, 2025. Accessed January 14, 2025. https://investors.biogen.com/news-releases/news-release-details/fda-accepts-leqembir-lecanemab-irmb-biologics-license

2. Eisai Completes Rolling Biologics License Application to FDA for Subcutaneous Maintenance Dosing Option of Leqembi for Alzheimer Disease. PharmExec. November 1, 2024. Accessed January 14, 2025. https://www.pharmexec.com/view/eisai-completes-rolling-biologics-license-application-fda-subcutaneous-maintenance-dosing-option-leqembi-alzheimer-disease

3. Eisai Presents Full Results of Lecanemab Phase 3 Confirmatory Clarity Ad Study for Early Alzheimer’s Disease At Clinical Trials On Alzheimer’s Disease (Ctad) Conference. Biogen. November 29, 2022. Accessed January 14, 2025. https://investors.biogen.com/news-releases/news-release-details/eisai-presents-full-results-lecanemab-phase-3-confirmatory

4. Alzheimer's Disease Facts and Figures. Alzheimer’s Association. Accessed January 14, 2025. https://www.alz.org/alzheimers-dementia/facts-figures#:~:text=navigate%20dementia%20care.-,Prevalence,other%20dementias%20as%20older%20Whites.

5. Dementia. WHO. March 15, 2023. Accessed January 14, 2025. https://www.who.int/news-room/fact-sheets/detail/dementia