Lecanemab Data Suggest Sustained Delay in Alzheimer Disease Progression With Long-Term Maintenance Therapy

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New long-term analyses presented at the 18th Clinical Trials on Alzheimer’s Disease (CTAD) Conference suggest that continued treatment with lecanemab (LEQEMBI®) may substantially delay progression from mild cognitive impairment (MCI) due to Alzheimer disease (AD) to later disease stages. Findings also included new safety and efficacy data on a subcutaneous formulation currently under regulatory review in the US.

Eisai and Biogen reported updated modeling results estimating “time savings,” or delay in disease progression, based on data from the open-label extension (OLE) of the Clarity AD trial and 16 monoclonal antibody studies. Using Alzheimer’s Disease Neuroimaging Initiative data as the untreated comparator, investigators found that both earlier treatment initiation and continued long-term therapy were associated with larger delays in clinical worsening.

Progression Delays With Continued Lecanemab Treatment

Across analyses, continued lecanemab therapy slowed progression from MCI due to AD to mild and moderate AD:

• Progression from MCI to mild AD:
  • Untreated group: 7.2 years
  • Lecanemab group: 9.7 years (time savings, 2.5 years)
  • Low-amyloid subgroup (PET <60 centiloids): 13.2 years (time savings, 6.0 years)
• Progression from MCI to moderate AD:
  • Untreated group: 10.1 years
  • Lecanemab group: 13.6 years (time savings, 3.5 years)
  • Low-amyloid subgroup: 18.4 years (time savings, 8.3 years)

According to the press release, these findings indicate that “earlier initiation of lecanemab treatment may provide a greater delay in disease progression,” and that each additional year of treatment “could further delay disease progression compared to stopping treatment.”

Subcutaneous Formulation Results Show Bioequivalence to IV Dosing

New data on the subcutaneous formulation (SC-AI), approved in August 2025 for maintenance dosing in the US, were also presented.1,2 Weekly 500 mg SC dosing (two 250 mg injections) demonstrated bioequivalent drug exposure to intravenous 10 mg/kg every two weeks (exposure ratio, 104%; 90% CI, 99.1%–109%).

Modeling suggested comparable amyloid removal and similar predicted ARIA-E incidence between SC and IV routes (overall 12.4%; 30.9% in ApoE4 homozygotes). In the safety analysis of participants previously exposed to IV lecanemab:

• Systemic infusion reactions:
  • 0% with 500 mg SC
  • 1.4% among those starting 720 mg SC by vial
  • 26.4% in the IV group
• Anti-drug antibodies: 1.4%

Investigators reported that the subcutaneous option “maintains efficacy with a low incidence of systemic infusion reactions, and is otherwise equivalent to conventional IV administration.”

Regulatory Status

Lecanemab is approved in 51 countries for indications including slowing progression of MCI and mild dementia due to AD. In the US, IV maintenance dosing every 4 weeks is approved, and the rolling supplemental Biologics License Application for SC initiation treatment was completed in November 2025. A subcutaneous formulation application was submitted in Japan the same month.

References:

1. Eisai Presents New Data on the Continued and Expanding Benefit of LEQEMBI® (lecanemab-irmb) Maintenance Treatment in Early Alzheimer’s Disease at CTAD 2025. News release. Eisai. December 4, 2025. Accessed December 5, 2025. https://www.eisai.com/news/2025/news202585.html
2. FDA Approves Subcutaneous Leqembi Autoinjector for Maintenance Therapy in Early Alzheimer Disease. Patient Care Online Editorial Staff. September 1, 2025. Accessed December 5, 2025. https://www.patientcareonline.com/view/fda-approves-subcutaneous-leqembi-autoinjector-for-maintenance-therapy-in-early-alzheimer-disease