The FDA has approved a supplemental Biologics License Application (sBLA) for Leqembi (lecanemab-irmb), allowing for a once-every-four-weeks intravenous (IV) maintenance dose for patients with early Alzheimer's disease. This approval, announced by Eisai and Biogen, offers a more convenient dosing schedule following the initial biweekly treatment phase.
This decision provides patients who have completed the biweekly initiation phase of 18 months the option to transition to a once-every-four-weeks 10 mg/kg dosing regimen, potentially improving long-term treatment adherence. The approval is based on data from Phase 2 and Clarity AD studies, demonstrating that the new regimen maintains the treatment’s clinical and biomarker benefits.
Clinical Data Supporting the Approval
The sBLA for the once-every-4-week dosing regimen is based on modeling of observed data from the Phase 2 study and its long-term extension (LTE) as well as the Clarity AD study and its LTE study. Modeling simulations predict that transitioning to once every four weeks maintenance dosing after 18 months of biweekly treatment will maintain clinical and biomarker benefits of therapy.
Data from the off-treatment period between the Phase 2 core study and its long-term extension (LTE) showed that discontinuation of treatment is associated with reaccumulation of brain amyloid, and plasma and CSF biomarkers, and reversion to placebo rate of clinical decline. In the Clarity AD core study (18 months), the mean change from baseline between the once every two weeks lecanemab treated group and the placebo group was -0.45 (P<0.0001) on the primary endpoint of the Clinical Dementia Rating-Sum of Boxes (CDR-SB) global cognitive and functional scale.
Over three years of treatment across the Clarity AD core study and LTE, LEQEMBI reduced cognitive decline on the CDR-SB by -0.95 relative to a matched natural history cohort, showing clinically meaningful benefit for early AD patients.
Leqembi's Mechanism of Action
Alzheimer's disease is caused by a continuous underlying neurotoxic process that begins before and continues after plaque removal. Continuous administration of Leqembi is of great value to patients as Leqembi works to fight Alzheimer's Disease in two ways: not only rapidly clearing the amyloid-beta (Aβ) plaque, but it also works to fight the progressive nature of Alzheimer's disease by continuously clearing the highly toxic protofibrils that otherwise continue to cause neuronal injury.
Global Approvals and Future Subcutaneous Option
Leqembi is approved in the U.S., Japan, China, Great Britain and several other markets. In November 2024, the treatment received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommending approval. Eisai has submitted applications for approval of lecanemab in 17 countries and regions. Furthermore, the FDA accepted Eisai's Supplemental Biologics License (BLA) for the Leqembi subcutaneous autoinjector for weekly maintenance dosing in January 2025 and set a PDUFA action date for August 31, 2025.
Collaboration and Development
Leqembi is the result of a long-standing collaboration between BioArctic and Eisai, and the antibody was originally developed by BioArctic based on the work of Professor Lars Lannfelt and his discovery of the Arctic mutation in Alzheimer's disease. Eisai is responsible for the clinical development, applications for market approval and commercialization of Lecanemab for Alzheimer's disease. BioArctic has the right to jointly commercialize Leqembi in the Nordic region, pending European approval, and currently Eisai and BioArctic are preparing for a joint commercialization in the region.
