About Lecanemab

About lecanemab (LEQEMBI®)
Lecanemab is the result of a strategic research alliance between Eisai and BioArctic. It is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ).

Lecanemab is approved and being marketed in the U.S., Japan, China, South Korea, Hong Kong, Israel, the United Arab Emirates, United Kingdom, Mexico, Macao, Oman, Taiwan, Europe Union, and Qatar 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). Lecanemab is under regulatory review in 12 countries. In January 2025, the supplemental Biologics License Application (sBLA) for intravenous (IV) maintenance dosing of the treatment was approved in the U.S. After an 18 months initiation phase with once every two weeks of dosing, a transition to the maintenance dosing regimen of 10 mg/kg once every four weeks or continuing 10 mg/kg once every two weeks may be considered. Additionally, the U.S. Food and Drug Administration (FDA) accepted Eisai’s Biologics License Application (BLA) for the LEQEMBI® subcutaneous autoinjector for weekly maintenance dosing in January 2025 and set a PDUFA action date for August 31, 2025.

Since July 2020 the Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains, is ongoing. AHEAD 3-45 is conducted as a public-private partnership between the Alzheimer’s Clinical Trial Consortium that provides the infrastructure for academic clinical trials in AD and related dementias in the U.S, funded by the National Institute on Aging, part of the National Institutes of Health, Eisai and Biogen. Since January 2022, the Tau NexGen clinical study for Dominantly Inherited AD (DIAD), that is conducted by Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, is ongoing and includes lecanemab as the backbone anti-amyloid therapy.

About Clarity AD

Study title A Study to Confirm Safety and Efficacy of Lecanemab in Participants With Early AD (Clarity AD)
Study population 1,795 participants of mild cognitive impairment (MCI) due to AD and mild AD (collectively known as early AD) with confirmed presence of amyloid pathology in the brain in the global study, and an additional 111 subjects ongoing in China.
Treatment administered 10 mg/kg bi-weekly of lecanemab
Duration of treatment 18 months
Study locations Singapore, South Korea, Japan, the U.S., Europe, China and others
Primary endpoint Change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 18 months
Key secondary endpoints Change From Baseline in Amyloid Positron Emission Tomography (PET) using Centiloids, AD Assessment Scale – Cognitive Subscale 14 (ADAS-Cog14*), AD Composite Score (ADCOMS**) and AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL***) at 18 months

* ADAS-Cog is the most common cognitive assessment instrument used in AD clinical trials all over the world. ADAS-Cog14 consists of 14 competencies: word recall, commands, constructional praxis, object and finger naming, ideational praxis, orientation, word recognition, remembering word recognition instructions, comprehension of spoken language, word finding difficulty, spoken language ability, delayed word recall, number cancellation, and maze task. ADAS-Cog has been used in clinical trials for earlier stages of AD including MCI.

** Developed by Eisai, combines items from the ADAS-Cog scale for assessing cognitive functions, MMSE and the CDR scale for evaluating the severity of dementia to enable highly sensitive detection of changes in clinical functions of early AD symptoms and changes in memory.

*** ADCS MCI-ADL assesses the competence of patients with MCI in activities of daily living (ADLs), based on 24 questions to the patient’s partner about actual recent activities of daily living.

Lecanemab treatment met the primary endpoint and reduced clinical decline on the global cognitive and functional scale, CDR-SB, compared with placebo at 18 months by 27%, which represents a treatment difference in the score change of -0.45 (p=0.00005) in the analysis of Intent-to-treat (ITT) population. Starting as early as six months, across all time points, the treatment showed highly statistically significant changes in CDR-SB from baseline compared to placebo (all p-values are less than 0.01). All key secondary endpoints were also met with highly statistically significant results compared with placebo (p<0.01). Key secondary endpoints were the change from baseline at 18 months compared with placebo of treatment in amyloid levels in the brain measured by amyloid positron emission tomography (PET), the AD Assessment Scale-cognitive subscale14 (ADAS-Cog14), AD Composite Score (ADCOMS) and the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL).

The incidence of amyloid-related imaging abnormalities-edema/effusion (ARIA-E), an adverse event associated with anti-amyloid antibodies, was 12.5% in the lecanemab group and 1.7% in the placebo group. The incidence of symptomatic ARIA-E was 2.8% in the lecanemab group and 0.0% in the placebo group. The ARIA-H (ARIA cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis) rate was 17.0% in the lecanemab group and 8.7% in the placebo group. The incidence of symptomatic ARIA-H was 0.7% in the lecanemab group and 0.2% in the placebo group. There was no imbalance in isolated ARIA-H (i.e., ARIA-H in patients who did not also experience ARIA-E) between lecanemab (8.8%) and placebo (7.6%). The total incidence of ARIA (ARIA-E and/or ARIA-H) was 21.3% in the lecanemab group and 9.3% in the placebo group. Overall, lecanemab’s ARIA incidence profile was within expectations.

About Sub-Analysis of the Clarity AD trials involving an Asian Cohort13
In a sub-analysis of the Clarity AD trials involving an Asian cohort (N = 294) from Japan, South Korea, and Singapore, lecanemab demonstrated efficacy consistent with the overall study population. For the primary endpoint, lecanemab showed a slower decline in CDR-SB at 18 months compared to placebo in the Asian region (adjusted mean difference: -0.349; 95% confidence intervals: -0.773, 0.076; 24% reduction in decline). Secondary efficacy endpoints also favored lecanemab over placebo in the Asian cohort. Lecanemab was well tolerated among Asian participants, with a safety profile similar to that of the overall Clarity AD population. The most common adverse events of special interest included ARIA-H (lecanemab: 14.4%; placebo: 16.2%), ARIA-E (lecanemab: 6.2%; placebo: 1.4%), and infusion-related reactions (lecanemab: 12.3%; placebo: 1.4%). The incidence of adverse events leading to study drug dose interruption or withdrawal, infusion-related reactions, ARIA-E, and ARIA-H was lower in the lecanemab-treated group in the Asian region compared to the overall Clarity AD population. Quality of life and biomarker assessments in the Asian region were generally similar to those in the overall Clarity AD population.

References

  1. LEQEMBI® (lecanemab) Prescribing Information, Eisai (Singapore) Pte Ltd. Approval date 2 May 2025.
  2. van Dyck, C.H., et al. Lecanemab in Early Alzheimer’s Disease.New England Journal of Medicine. 2023;388:9-21. .https://www.nejm.org/doi/full/10.1056/NEJMoa2212948
  3. Johannesson, M., et al. Lecanemab demonstrates highly selective binding to Aβ protofibrils isolated from Alzheimer’s disease brains. Molecular and Cellular Neuroscience. 2024;130:103949. https://doi.org/10.1016/j.mcn.2024.103949
  4. Sehlin, D., et al. Large aggregates are the major soluble Aβ species in AD brain fractionated with density gradient ultracentrifugation. PLoS One. 2012;7(2):e32014. https://doi.org/10.1371/journal.pone.0032014
  5. Söderberg, L., et al. Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer’s Disease. Neurotherapeutics. 2022;20(1):195-206. https://doi.org/10.1007/s13311-022-01308-6
  6. Selkoe, D. Does the Current Evidence for Lecanemab Mechanism Support a Rationale for Continued Lecanemab Dosing? Presented at Alzheimer’s Association International Conference, 2024.
  7. Amin, L., Harris, D.A. Aβ receptors specifically recognize molecular features displayed by fibril ends and neurotoxic oligomers. Nature Communications. 2021;12:3451. doi:10.1038/s41467-021-23507-z.
  8. Ono, K., Tsuji, M. Protofibrils of Amyloid-β are Important Targets of a Disease-Modifying Approach for Alzheimer’s Disease. International Journal of Molecular Sciences. 2020;21(3):952. https://doi.org/10.3390/ijms21030952
  9. Noguchi-Shinohara, M. and Shuta, K, et al. Lecanemab-Associated Amyloid-β Protofibril in Cerebrospinal Fluid Correlates with Biomarkers of Neurodegeneration in Alzheimer’s Disease. Annals of Neurology. 2025; in press. https://doi.org/10.1002/ana.27175
  10. 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. Available at: https://www.eisai.co.jp/news/2022/news202285.html
  11. Towards a dementia-inclusive Singapore FULL REPORT Available at: https://nvpc.org.sg/wp-content/uploads/2022/04/Dementia-Colabs-Public-Report-5-April-2022.pdf
  12. WHO Fact Sheets detail dementia Available at: https://www.who.int/news-room/fact-sheets/detail/dementia
  13. Christopher Chen, Sadao Katayama, Jae-Hong Lee, et al. Clarity AD: Asian regional analysis of a phase III trial of lecanemab in early Alzheimer’s disease, The Journal of Prevention of Alzheimer’s Disease, 2025, doi.org/10.1016/j.tjpad.2025.100160.