EISAI TO PRESENT NEW DATA FROM LEQEMBI® (LECANEMAB-IRMB) PHASE 3 CLARITY AD STUDY AND OTHER ALZHEIMER’S DISEASE PIPELINE RESEARCH AT THE CLINICAL TRIALS ON ALZHEIMER'S DISEASE (CTAD) CONFERENCEUpdate on LEQEMBI Investigational Subcutaneous Formulation

Presentation Title
Clarity AD: Review of the Mechanism-Based Rationale and Results of the Lecanemab Phase 3 Trial
Biomarker Assessments from Clarity AD: A Focus on Downstream Implications of Targeting Protofibrils* and Tau as a Predictive Biomarker
Lecanemab for the Treatment of Early Alzheimer’s Disease: The Extension of Efficacy Results from Clarity AD
Preliminary Update on Lecanemab Safety in Clarity AD Open-Label Extension, Including Subcutaneous Formulation
Panel discussion, Q&A

   

■ Oral Presentations

 

■ Poster Presentations

   

This release discusses investigational uses of agents in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that such investigational agents will successfully complete clinical development or gain health authority approval.

　

*Protofibrils

• One of the AD pathological features is the accumulation of clusters (plaques) of amyloid beta (Aβ) in the brain. The formation of these plaques is the result of a continuous process by which individual Aβ proteins join together, latching onto each other, one at a time, like adding links to a chain.⁹ In the early part of this process these small chains of Aβ are soluble and are toxic to the nerves within the brain.^10,11 
• • The most toxic of the soluble chains is called a protofibril^.3 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.^1,2
• • 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.¹²

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[Notes to editors]

1. 1.    About Lecanemab (generic name, U.S. brand name: LEQEMBI^®),

Lecanemab is the result of a strategic research alliance between Eisai and BioArctic. Lecanemab is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). In the U.S., LEQEMBI was granted traditional approval by the U.S. Food and Drug Administration (FDA) on July 6, 2023. LEQEMBI is an amyloid beta-directed antibody indicated as a disease-modifying treatment for Alzheimer’s disease (AD) in the U.S. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment (MCI) or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. In Japan, Eisai received approval from the Ministry of Health, Labour and Welfare (MHLW) on September 25, 2023 to manufacture and market lecaenmab as a treatment for slowing progression of MCI and mild dementia due to AD.

 

Please see full Prescribing Information, including Boxed WARNING in the United States.

 

Eisai has also submitted applications for approval of lecanemab in EU, China, Canada, Great Britain, Australia, Switzerland, South Korea and Israel. In China and Israel, the applications have been designated for priority review, and in Great Britain, lecanemab has been designated for the Innovative Licensing and Access Pathway (ILAP), which aims to reduce the time to market for innovative medicines.

 

Eisai has completed a lecanemab subcutaneous bioavailability study, and subcutaneous dosing is currently being evaluated in the Clarity AD (Study 301) open-label extension (OLE). A maintenance dosing regimen has been evaluated as part of Study 201.

 

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.

 

1. 2.   About E2511

E2511 is Eisai’ s in-house discovered and developed investigational novel molecule that directly binds to tropomyosin receptor kinase A (TrkA); a nerve growth factor (NGF) located on the neural cell membrane. E2511 could potentially promote recovery and synaptic remodeling of damaged cholinergic neurons. A Phase 1 study for E2511 is underway.

 

1. 3.    About the Collaboration between Eisai and Biogen for Alzheimer’s Disease

Eisai and Biogen have been collaborating on the joint development and commercialization of AD treatments since 2014. Eisai serves as the lead of lecanemab development and regulatory submissions globally with both Eisai and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making authority. In Japan, Eisai and Biogen Japan will co-promote lecanemab, with Eisai distributing the product as the Marketing Authorization Holder.

 

1. 4.    About the Collaboration between Eisai and BioArctic for Alzheimer’s Disease

Since 2005, Eisai and BioArctic have had a long-term collaboration regarding the development and commercialization of AD treatments. Eisai obtained the global rights to study, develop, manufacture and market LEQEMBI for the treatment of AD pursuant to an agreement with BioArctic in December 2007. The development and commercialization agreement on the antibody LEQEMBI back-up was signed in May 2015.

 　

References

• ¹

  LEQEMBI US Prescribing Information under Traditional Approval

• ²

  Alzheimer's Association, Facts & Figures 2023. https://www.alz.org/media/Documents/alzheimers-facts-and-figures.pdf Accessed October 12, 2023.

• ³

  Hampel, H., Hardy, J., Blennow, K. et al. The Amyloid-β Pathway in Alzheimer’s Disease. Mol Psychiatry. 2021;26:5481–5503. https://doi.org/10.1038/s41380-021-01249-0

• ⁴

  van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388(1):9-21.

• ⁵

  Brendza RP, et al. Anti-Aβ antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice J Clin Invest. 2005;115(2):428-433. https://doi.org/10.1172/JCI23269.

• ⁶

  Ono K, Tsuji M. Protofibrils of Amyloid-β are Important Targets of a Disease-Modifying Approach for Alzheimer's Disease. Int J Mol Sci. 2020;21(3):952. Doi: 10.3390/ijms21030952. PMID: 32023927; PMCID: PMC7037706.

• ⁷

  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 2023 20:195–206 https://doi.org/10.1007/s13311-022-01308-6 Accessed October 12, 2023.

• ⁸

  Hartley DM, Walsh DM, Ye CP, Diehl T, Vasquez S, Vassilev PM, Teplow DB, Selkoe DJ. Protofibrillar intermediates of amyloid beta-protein induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons. J Neurosci. 1999;19(20):8876-84. doi: 10.1523/JNEUROSCI.19-20-08876.1999. PMID: 10516307; PMCID: PMC6782787.

• ⁹

  Alzheimer’s Association. (2022). Brain Tour Part 2 - Alzheimer’s Effect. Retrieved September 27, 2023, from https://www.alz.org/alzheimers-dementia/what-is-alzheimers/brain_tour_part_2

• ¹⁰

  Chen, Gf., Xu, Th., Yan, Y. et al. Amyloid beta: structure, biology and structure-based therapeutic development. Acta Pharmacol. 2017;38:1205. https://doi.org/10.1038/aps.2017.28
  

• ¹¹

  Habashi M., Vulta S., Tripathi K., et al. Early diagnosis and treatment of Alzheimer’s disease by targeting toxic soluble Aβ oligomers. Biophysics and Computational Biology. 2022;10.1073. https://www.pnas.org/doi/epdf/10.1073/pnas.2210766119

• ¹²

  Amin L, Harris DA. Aβ receptors specifically recognize molecular features displayed by fibril ends and neurotoxic oligomers. Nat Commun. 2021;12:3451. doi:10.1038/s41467-021-23507-z