FDA Approves LEQEMBI® IV Maintenance Dosing for Early Alzheimer’s Treatment

Eisai Co., Ltd. and Biogen Inc. announced that the U.S. Food and Drug Administration (FDA) has approved the Supplemental Biologics License Application (sBLA) for once every four weeks lecanemab-irmb intravenous (IV) maintenance dosing. LEQEMBI is indicated for the treatment of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) or mild dementia stage of disease (collectively referred to as early AD) in the U.S. After 18 months of once every two weeks initiation phase, a transition to the maintenance dosing regimen of 10 mg/kg once every four weeks may be considered or the regimen of 10 mg/kg once every two weeks may be continued.

The sBLA is based on modeling of observed data from the Phase 2 study (Study 201) and its long-term extension (LTE) as well as the Clarity AD study (Study 301) and its LTE study. Modeling simulations predict that transitioning to once every four weeks maintenance dosing after 18 months of once every two weeks treatment will maintain clinical and biomarker benefits of therapy. AD is a progressive, relentless disease caused by a continuous underlying neurotoxic process that begins before and continues after plaque removal.^1,2,3 Only LEQEMBI works to fight AD in two ways: continuously clearing protofibrils and rapidly clearing plaque. This is important because with continuous administration, LEQEMBI clears highly toxic protofibrils* which can continue to cause neuronal injury even after the amyloid-beta (Aβ) plaque has been cleared from the brain.

Importance of Ongoing Treatment

• Data from the off-treatment period between the Study 201 (Phase 2) core study and LTE showed that discontinuation of treatment is associated with reaccumulation of amyloid PET and plasma and CSF biomarkers, and reversion to placebo rate of clinical decline.⁴
• For maintenance treatment, once every four weeks dosing regimen may be easier than once every two weeks dosing for patients and care partners to continue treatment for early AD.
• Ongoing treatment can slow disease progression and prolong the benefit of therapy,⁴ with the goal of helping patients maintain who they are for longer.
• 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.
  
  • A change from 0.5 to 1 on the CDR score domains of Memory, Community Affairs and Home/Hobbies is the difference between slight impairment and loss of independence, such as people's ability to be left alone, remember recent events, participate in daily activities, complete household chores, function independently and engage in hobbies and intellectual interests.

LEQEMBI is approved in the U.S., Japan, China, South Korea, Hong Kong, Israel, UAE, Great Britain, Mexico and Macau. 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. Additionally, 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.

Eisai serves as the lead for lecanemab’s development and regulatory submissions globally with both Eisai and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making authority.

*Protofibrils are believed to contribute to the brain injury that occurs with AD and are considered to be the most toxic form of Aβ, having a primary role in the cognitive decline associated with this progressive, debilitating condition.⁵ Protofibrils cause injury to neurons in the brain, which in turn, can negatively impact cognitive function via multiple mechanisms, not only increasing the development of insoluble Aβ plaques but also increasing direct damage to brain cell membranes and the connections that transmit signals between nerve cells or nerve cells and other cells. It is believed the reduction of protofibrils may prevent the progression of AD by reducing damage to neurons in the brain and cognitive dysfunction.⁶  

**The lecanemab group was compared to the expected decline based on the Alzheimer's Disease Neuroimaging Initiative (ADNI) group. ADNI is a clinical research project launched in 2005 to develop methods to predict the onset of AD and to confirm the effectiveness of treatments. The ADNI observational cohort represents the exact population of those in Clarity AD study; matched ADNI participants show similar degree of decline to placebo group out to 18 months, supporting the appropriateness of the matching.