Eisai and Biogen have 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's disease (AD) treatment. This application aims to provide a more convenient, at-home administration option for patients with mild cognitive impairment (MCI) or mild dementia due to AD. The FDA has granted Fast Track designation to the application.
The BLA is supported by data from the Clarity AD study, a placebo-controlled, double-blind, parallel-group trial with an 18-month open-label extension phase. The study involved 1,795 participants with MCI or early-stage AD and compared Leqembi to placebo. The primary endpoint was the Clinical Dementia Rating Sum of Boxes (CDR-SB), a global cognitive and functional scale.
Clarity AD Trial Results
Results from the Clarity AD trial indicated that patients treated with Leqembi experienced a 27% slowing of cognitive and functional decline over 18 months, as measured by the CDR-SB. The study also showed significant improvements in key secondary outcomes, including measures of amyloid burden, cognition, and daily functioning.
Common adverse events (AEs) associated with Leqembi included infusion reactions and amyloid-related imaging abnormalities (ARIA). Deaths occurred in 0.7% and 0.8% of participants in the Leqembi and placebo groups, respectively; no deaths were related to Leqembi or occurred with ARIA. The drug is contraindicated in patients with serious hypersensitivity to any of its excipients and can cause ARIA-E and ARIA-H, which can occur together, and intracerebral hemorrhage.
Subcutaneous Formulation Benefits
Biogen has stated that the SC formulation is designed to sustain effective drug levels that continue to clear neurotoxic amyloid-beta protofibrils post-plaque clearance. The administration time is approximately 15 seconds per dose. If approved, the SC formulation could improve convenience, reduce infusion site visits, and support ongoing therapy and its clinical and biomarker benefits.
Alzheimer's Disease Burden
Globally, over 55 million people live with dementia, with Alzheimer's accounting for 60% to 70% of cases. The World Health Organization reports 10 million new cases annually. Alzheimer's is the seventh leading cause of death and a major cause of disability and dependency among older people. Alzheimer’s Disease International estimates that the number of people with AD will reach 78 million by 2030 and 139 million by 2050. The worldwide cost of dementia was $818 billion in 2015, rising to over $1.3 trillion, and is expected to reach $2.8 trillion by 2030.
Current Leqembi Approvals and Future Plans
Leqembi is currently approved in the United States, Japan, China, South Korea, Hong Kong, Israel, United Arab Emirates, and the United Kingdom. A supplemental BLA is under FDA review for monthly IV dosing, with a decision expected by January 2025.
