Eisai Completes Rolling Biologics License Application to FDA for Subcutaneous Maintenance Dosing Option of Leqembi for Alzheimer Disease

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Eisai and Biogen announced the completion of a rolling submission to the FDA for a Biologics License Application (BLA) for a subcutaneous (SC) maintenance dosing option of Leqembi (lecanemab-irmb), an Alzheimer disease (AD) treatment for patients with mild cognitive impairment (MCI) or mild dementia. According to Biogen, the application, which was granted FDA Fast Track designation, builds upon data from the Clarity AD study. The BLA seeks to enable weekly home or facility-administered SC doses via autoinjector for patients who have finished initial intravenous treatments.¹

The placebo-controlled, double-blind, parallel-group, 18-month, open-label extension phase of the Clarity AD trial was designed to confirm the safety and efficacy of Leqembi compared to placebo in patients with early AD.² The study included 1,795 participants with MCI or early-stage AD.³ The primary endpoint of the study was global cognitive and functional scale, Clinical Dementia Rating Sum of Boxes (CDR-SB).¹

Results found that patients treated with Leqembi demonstrated a 27% slowing of cognitive and functional decline over 18 months, as measured by the CDR-SB. Key secondary outcomes, including measures of amyloid burden, cognition, and daily functioning, also showed significant improvement.

Common adverse events (AEs) included infusion reactions, amyloid-related imaging abnormalities (ARIA), headache, and falling. During the study, deaths occurred in 0.7% and 0.8% of participants in the Leqembi and placebo groups, respectively, and no deaths were related to Leqembi or occurred with amyloid-related imaging abnormalities. Eisai and Biogen warn that Leqembi is contraindicated in patients with serious hypersensitivity to any of its excipients. Additionally, it can cause ARIA-E and ARIA-H, which can occur together, and intracerebral hemorrhage.^1,3

Biogen stated that the SC formulation is designed to sustain effective drug levels that continue to clear neurotoxic amyloid-beta protofibrils post-plaque clearance, with administration taking about 15 seconds per dose. Further, the company stated that if the SC formulation is approved, it could improve convenience and reduce infusion site visits, supporting ongoing therapy and its clinical and biomarker benefits.¹

According to the World Health Organization, there are currently more than 55 million people living with dementia globally. Sixty percent of people living with dementia are in low- and middle-income countries, and there are 10 million new cases reported annually. AD accounts for anywhere from 60% to 70% of all cases of dementia. It is also the seventh leading cause of death and one of the major causes of disability and dependency among older people globally. Women experience higher disability-adjusted life years and mortality due to dementia, but also provide 70% of care hours for people living with the condition.⁴

According to Alzheimer’s Disease International, the number of people with AD doubles every 20 years, with numbers expected to reach 78 million by 2030 and 139 million in 2050. In 2015, the total estimated worldwide cost of dementia was $818 billion, which has risen to more than $1.3 trillion and is expected to rise to $2.8 trillion by 2030.⁵

Currently, Leqembi is approved in the United States, Japan, China, South Korea, Hong Kong, Israel, United Arab Emirates, and the United Kingdom. Currently, a supplemental BLA is under FDA review for monthly IV dosing, with a decision expected by January 2025.¹

References

1. Eisai Completes Rolling Submission to US FDA for LEQEMBI® (lecanemab-irmb) Biologics License Application for Subcutaneous Maintenance Dosing for the Treatment of Early Alzheimer’s Disease Under the Fast Track Status. Biogen. October 31, 2024. Accessed November 1, 2024. https://investors.biogen.com/news-releases/news-release-details/eisai-completes-rolling-submission-us-fda-leqembir-lecanemab

2. A Study to Confirm Safety and Efficacy of Lecanemab in Participants With Early Alzheimer's Disease (Clarity AD). Clinicaltrials.gov. Accessed November 1, 2024. https://clinicaltrials.gov/study/NCT03887455

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, 2024. Accessed November 1, 2024. https://investors.biogen.com/news-releases/news-release-details/eisai-presents-full-results-lecanemab-phase-3-confirmatory

4. Dementia. WHO. March 15, 2023. Accessed November 1, 2024. https://www.who.int/news-room/fact-sheets/detail/dementia

5. Dementia statistics. Alzheimer’s Disease International. Accessed November 1, 2024. https://www.alzint.org/about/dementia-facts-figures/dementia-statistics/