EISAI TO PRESENT DUAL-ACTING LECANEMAB THREE YEAR EFFICACY AND SAFETY DATA AND DISCUSS LONG-TERM OUTCOMES OF CONTINUED TREATMENT AT THE ALZHEIMER'S ASSOCIATION INTERNATIONAL CONFERENCE 2024
EISAI TO PRESENT DUAL-ACTING LECANEMAB THREE YEAR EFFICACY AND SAFETY DATA AND DISCUSS LONG-TERM OUTCOMES OF CONTINUED TREATMENT AT THE ALZHEIMER'S ASSOCIATION INTERNATIONAL CONFERENCE 2024
Latest findings from Eisai's robust Alzheimer's disease (AD) pipeline will be shared, including the importance of continued treatment of AD, which is a progressive neurodegenerative disease that begins before plaque deposition and continues after plaque removal
艾松製藥公司強大的阿爾茨海默病(AD)研究成果將予以分享,包括持續治療AD的重要性,這是一種神經退行性疾病,起源於斑塊沉積之前,在斑塊清除後仍會繼續發展。
TOKYO, July 22, 2024 /PRNewswire/ -- Eisai Co. Ltd (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") announced today that the company will present the latest findings on its Alzheimer's disease (AD) pipeline and research, including our dual-acting, anti-amyloid beta (Aβ) protofibril* antibody for the treatment of AD, lecanemab (generic name, U.S. brand name: LEQEMBI), at the Alzheimer's Association International Conference (AAIC). Dual-acting lecanemab is the only early AD treatment available to support neuronal function by clearing the highly toxic protofibrils that continue to cause neuronal injury and death even after plaques have been cleared from the brain. The conference will be held in Philadelphia and virtually from July 28 to August 1, 2024. Eisai will present data and research in four (4) oral and 15 poster presentations at the meeting and will host two (2) sessions on lecanemab.
2024年7月22日,東京/ PRNewswire/ - 來自艾松藥品株式會社(總部位於東京,首席執行官:內藤春夫,以下簡稱“艾松”)的最新阿爾茨海默病(AD)研究成果及藥物研究將在阿爾茨海默病協會國際會議(AAIC)上發佈,包括我們的雙重作用抗澱粉樣-β(Aβ)原纖維蛋白*抗體——治療AD的樂卡那莫(通用名,美國商品名:LEAEMB),它是第一種可清除引起神經損傷和死亡的極其有毒的原纖維和寡聚體的早期AD治療方法,即使從大腦中清除了斑塊。會議將於2024年7月28日至8月1日在費城和虛擬環境中舉行。艾松公司將在會議上發佈4項演講和15份海報,並就樂卡那莫主持兩個會議。
Perspectives Session: Does the Current Evidence Base Support Lecanemab Continued Dosing for Early Alzheimer's Disease?
透視會議 :當前證據是否支持樂卡那莫繼續用於早期阿爾茨海默病的治療?
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On July 30 from 4:15 p.m. to 5:45 p.m. EDT, Eisai will present the latest data exploring three critical topics:
Does the current evidence for lecanemab mechanism support a rationale for continued lecanemab dosing?
Is the lecanemab maintenance dosing regimen supported by simulation models?
Is there evidence for a continued benefit for long-term lecanemab treatment?
Dennis Selkoe, M.D., will focus on the toxicity of soluble aggregated amyloid-beta species, including oligomers, protofibrils and diffusible fibrils. The session will review the latest data on the mechanism of action of lecanemab, which binds to protofibrils and oligomers that continue to be produced even after plaques are cleared. Additional discussion will focus on the potential mechanistic justification for ongoing treatment to maintain clinical and biomarker efficacy.
Data from an intervening off-treatment period (gap period) occurring after the completion of the core phase of the Phase II Study 201 and before the initiation of the open-label extension (OLE) suggested the importance of continued administration of lecanemab. Youfang Cao, PhD., and Larisa Reyderman, Ph,D., from Eisai will present clinical pharmacology data and clinical pharmacology modeling outcomes that combine the outcomes from Study 201 and the Phase 3 Clarity AD study, which will provide insights into potential lecanemab maintenance dosing.
Christopher van Dyck, M.D., will present the latest 36-month efficacy and safety data from dual-acting lecanemab's Phase 3 Clarity AD core and OLE studies and panelists will discuss the potential benefits of continuous treatment of AD, which is a progressive, neurodegenerative disease that begins before plaque deposition and continues after plaque removal.
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在2024年7月30日下午4點15分至5點45分EDT,艾松將公佈最新數據,探討三個關鍵問題:
當前證據是否支持樂卡那莫機制有理由繼續使用
樂卡那莫維持用藥方案是否得到仿真模型的支持?
是否有繼續使用樂卡那莫進行長期治療的證據
Dennis Selkoe博士,將重點研究可溶性聚集澱粉樣-β物種,包括寡聚體、原纖維和可擴散的纖維。該會議將回顧樂卡那莫的作用機制的最新數據,樂卡那莫可以結合在斑塊清除後仍然會繼續產生的原纖維和寡聚體。同時還將討論持續治療以維持臨床和生物標誌物療效的潛在的機械化理由。
從II期研究201的核心階段完成後到開放標籤擴展(OLE)開始之前的干預性斷藥期間(間隔期)的數據表明繼續使用樂卡那莫是十分重要的。艾松的Youfang Cao博士和Larisa Reyderman博士將呈現臨床藥理學數據和混合II期研究201和III期Clarity AD研究的臨床藥理學建模結果,這將爲潛在的樂卡那莫維持用藥提供洞見。
Christopher van Dyck博士將展示雙重作用樂卡那莫的III期Clarity AD核心和OLE研究的最新36個月療效和安全性數據,小組討論將探討持續治療AD的潛在益處,這是一種先進的神經退行性疾病,在斑塊去除之前就開始了。
Featured Research Session: Beyond Amyloid Removal with Lecanemab Treatment: Update on Long-Term Imaging and Fluid Biomarkers.
特色板塊:樂卡那莫治療除澱粉樣物質清除之外的其他作用:長期成像和流動生物標誌物的更新。
In this Featured Research session on July 30 from 2:00 PM to 3:30 PM EDT, the latest findings on imaging and fluid biomarkers from dual-acting lecanemab treatment will be presented.
Brian Willis, PhD., and Arnaud Charil, PhD of Eisai will present the outcomes of recent PK/PD modeling examining the potential connection between dual-acting lecanemab's PK and amyloid PET, CDR-SB, and the outcomes of the tau PET from Carity AD core and OLE studies.
Nick Fox, M.D., FRCP, FMedSci, will explain the changes in brain volume that occur with anti-amyloid immunotherapy and its potential relationship to amyloid clearance.
Charlotte Teunissen, PhD., will present data on neurodegenerative biomarkers in plasma as a result of long-term treatment of dual-acting lecanemab, and will also explain the necessity for maintenance treatment from these changes in biomarkers.
在2024年7月30日下午2點至3點30分EDT的特色研究會議中,將介紹雙重作用樂卡那莫治療的成像和流動生物標誌物的最新研究結果。
艾松的Brian Willis博士和Arnaud Charil博士將展示最近的藥代動力學/藥效學建模結果,探討雙重作用樂卡那莫的藥代動力學特性與其從Clarity AD核心和OLE研究中得出的關於澱粉樣PEt、CDR-Sb和tau PEt的結局的關聯。
Nick Fox萬博士談到抗澱粉樣免疫療法引起的腦容積變化及其與澱粉樣清除的潛在關係。
Charlotte Teunissen博士將展示雙重作用樂卡那莫長期治療所產生的神經退變性生物標誌物數據,也將從這些生物標誌物變化中解釋維持治療的必要性。
"At AAIC 2024, Eisai will present the results from the Phase 2 and Phase 3 lecanemab studies and open label extensions exploring ongoing dosing with dual-acting lecanemab for potential longer-term clinical and biomarker benefit," said Michael Irizarry, M.D., Deputy Chief Clinical Officer and Senior Vice President of Clinical Research at Eisai Inc. "Alzheimer's disease (AD) is a progressive and relentless disease caused by a continuous underlying neurotoxic process. There is an urgency to treat because early and ongoing treatment can slow the progression of Alzheimer's disease. The earlier mild cognitive impairment (MCI) due to AD and mild AD dementia are diagnosed and treated, the greater the opportunity for the patient to benefit."
艾松公司副首席臨床官兼臨床研究高級副總裁Michael Irizarry萬博士表示:“在AAIC 2024上,艾松將公佈II期和III期樂卡那莫研究及開放標籤擴展的結果,探索持續用於樂卡那莫治療的時間長短對臨床和生物標誌物效益的潛在影響。阿爾茨海默病(AD)是一種進展性和無情的疾病,由於持續的神經毒性過程而引起。目前的計劃是儘早進行治療,持續進行治療可以延緩阿爾茨海默病的進程。越早診斷和治療由於AD和輕度AD癡呆而引起的輕度認知障礙(MCI)時,患者獲益的機會就越大。”
Key Presentation
■透視會議:7月30日下午4點15分至5點45分EDt,此次會議將回答 前證據是否支持樂卡那莫長期治療早期阿爾茨海默病?
■ Perspectives Session:
■透視會議:
Does the Current Evidence Base Support Lecanemab Continued Dosing for Early Alzheimer's Disease? From 4:15 PM to 5:45 PM EDT on July 30, 2024
當前證據是否支持樂卡那莫長期治療早期阿爾茨海默病? 2024年7月30日下午4點15分至5點45分EDt
Session Program
會議安排
Does the Current Evidence for Lecanemab Mechanism Support a Rationale for Continued Lecanemab Dosing?
Lecanemab機制的當前證據是否支持持續Lecanemab使用的合理性?
How Does the Latest Clinical Pharmacology Data & Modeling Support Continued Lecanemab Dosing?
最新的臨床藥理數據和模型如何支持持續使用Lecanemab?
Neuro-Dynamic Quantitative Systems Pharmacology (QSP) Model Supports Continued Lecanemab Treatment With Maintenance Dosing For Alzheimer's Disease
神經動態定量系統藥理(QSP)模型支持繼續使用Lecanemab維持劑量治療阿爾茨海默病
Is there Evidence for a Continued Benefit for Long-Term Lecanemab Treatment? A Benefit/Risk Update from Long-Term Efficacy, Safety and Biomarker Data
是否有持續長期Lecanemab治療的益處證據? 來自長期療效、安全性和生物標誌物數據的效益/風險更新
Q&A
問答
■ Featured Research Session
■ 特色研究會議
Beyond Amyloid Removal with Lecanemab Treatment: Update on Long-Term Imaging and Fluid Biomarkers From 2:00 PM to 3:30 PM EDT on July 30, 2024
除了澱粉樣蛋白去除外,Lecanemab治療的長期成像和液體生物標誌物更新。時間爲2024年7月30日下午2點到3點30分
Session Program
會議安排
Amyloid Plaque Reduction as a Biomarker of Efficacy: Assessment of Amyloid PET and Change in CDR-SB Utilizing Semi-Mechanistic Model
澱粉樣斑塊減少作爲效能的生物標誌: 利用半機制模型評估澱粉樣PET和CDR-Sb變化
Lecanemab Slows Tau PET Accumulation
Lecanemab減緩tau PET累積
"Paradoxical" Cerebral Volume Changes in Anti-Amyloid Immunotherapy Trials
抗澱粉樣免疫療法試驗中“自相矛盾”的腦容積變化
Long-Term Effects of Lecanemab on Biomarkers of Neurodegeneration in Plasma
Lecanemab對血漿神經退行性生物標誌物的長期影響
Q&A
問答
■ Oral Presentations
■ 口頭報告
Asset/Project, Presentation Date and Time (EDT, U.S) |
Topic, Abstract number |
Lecanemab |
Examining Lecanemab-Associated Amyloid-Beta Protofibril as a Proximal Biomarker of Neurodegeneration Unlike Other Plaque-Associated Biomarkers Abstract ID #94585 |
Lecanemab |
Lecanemab, Amyloid-Induced Tau Pathology as Supported CSF MTBR-tau243 in Clarity AD Abstract ID #95507 |
E2027 |
The Effects of the Novel Phosphodiesterase 9 (pde9) Inhibitor E2027 (irsenontrine) on CSF Proteomics Profile in Amyloid Positive and Amyloid Negative Lewy Body Dementia Abstract ID #91293 |
General AD |
Unmet Needs in the Diagnosis and Management of Early AD in Community-Based Settings in the United States Abstract ID #89135 |
資產/項目、演示日期和時間(美東時間,美國) |
主題,摘要編號 |
Lecanemab |
摘要編號#94585 Lecanemab |
Lecanemab |
Lecanemab,支持CSF MTBR-tau243的澱粉樣誘導的Tau病理學,清晰AD 摘要編號#95507 |
E2027 |
新型磷酸二酯酶9(PDE9)抑制劑E2027(irsenontrine)對澱粉樣陽性和澱粉樣陰性Lewy體癡呆的CSF蛋白質組學特徵的影響 摘要編號#91293 |
普通 AD |
美國社區中早期AD的診斷和管理需求未滿足 摘要編號#89135 |
■ Poster Presentations
■展板展示
Asset/Project, Presentation Date and Time (EDT, U.S) |
Topic, Abstract number |
Lecanemab |
Model-Based Assessment of Lecanemab Maintenance Dosing Regimen and Potential for Continued Suppression of Amyloid Plaque, Disease Progression |
E2814 July 30 (Tue) |
Crystal Structure of E2814 Bound to Tau Abstract ID #94773 |
E2511 |
Non-Clinical Evidence for Modulating Synaptic CSF Biomarkers by E2511: A Novel Small Compound TrkA Biased Positive Allosteric Modulator |
E2025 July 28 (Sun) |
E2025, A Novel Anti-EphA4 Antibody, Enhances EphA4 Cleavage, and Suppresses Tau Pathologies in a Transgenic Model of AD Abstract ID #94810 |
Biomarker |
Prediction of Regional Brain Tau Levels in Early Alzheimer's Disease Using Plasma pTau217 |
Biomarker |
A Prospective Multi-Clinic Implementation Science Study to Evaluate Use of Blood- Based Biomarkers as Confirmatory Diagnostic Tools for Early Alzheimer's Disease in Real-World Clinical Practice |
Biomarkers |
Advancing Early Detection of Alzheimer's Disease in the Primary Care Setting in the United States |
Imaging |
Volumes of Specific Substrates Within the Amygdala and Hippocampus are Impacted by Brain Amyloid-β Abstract ID #92024 |
General AD |
Total Healthcare Costs Across the Alzheimer's Disease Continuum in the United States (US) |
General AD |
Risk Factors for Mild Cognitive Impairment: Prediction Models Developed with Electronic Health Record Data Abstract ID #85564 |
General AD |
Patterns in the Diagnosis and Management of Early AD in Community-Based Settings in the United States |
General AD |
Usage Patterns of Anticoagulant Therapy in Patients with Mild Cognitive Impairment or Alzheimer's Disease |
General AD |
Adapting Healthcare Infrastructure for Disease-Modification in Early Alzheimer's Disease Abstract ID #94773 |
General AD |
Critical Path for Alzheimer's Disease (CPAD) Consortium: Data-Driven Solutions for Clinical Trial Design and Informed Decision Making Abstract ID #86145 |
General AD |
Expectations and Perspectives of Patients and Physicians on New Treatment for Early Alzheimer's Disease: Results of a Physician Survey and Patient Focus Group Interview Abstract ID #86956 |
資產/項目、演示日期和時間(美東時間,美國) |
主題,摘要編號 |
Lecanemab |
基於模型的Lecanemab維持劑量方案評估及持續抑制澱粉樣斑塊、疾病進展潛力 |
E2814 7月30日(星期二) |
E2814結合Tau的晶體結構 摘要 ID #94773 |
E2511 |
E2511:一種新型小分子化合物TrkA偏倚正變構調節劑對突觸CSF生物標誌物調節的非臨床證據 |
E2025 7月28日(星期日) |
E2025:一種新型抗EphA4抗體,增強EphA4切割,抑制AD轉基因模型中的tau病理 摘要 ID #94810 |
生物標誌物 |
使用血漿pTau217預測早期阿爾茨海默病的區域型腦tau水平 |
生物標誌物 |
一項前瞻性多診所實施科學研究,旨在評估血液基礎生物標誌物作爲早期阿爾茨海默病診斷工具在臨床實踐中的可行性 |
生物標誌物 |
在美國基層醫療場所推進阿爾茨海默病的早期檢測 |
成像 |
腦澱粉樣 β 影響杏仁體和海馬內特定底物的體積 摘要編號 #92024 |
普通 AD |
美國阿爾茨海默病連續體的總醫療保健成本 |
普通 AD |
使用電子健康記錄數據開發的輕度認知障礙預測模型的風險因素 摘要編號 #85564 |
普通 AD |
社區環境中早期 AD 的診斷和治療模式 |
普通 AD |
輕度認知障礙或阿爾茨海默病患者抗凝治療的使用模式 |
普通 AD |
爲早期阿爾茨海默病改善健康基礎設施的適應性 摘要 ID #94773 |
普通 AD |
阿爾茨海默病關鍵路徑(CPAD)聯盟:基於數據的臨床試驗設計和知情決策的解決方案 摘要ID#86145 |
普通 AD |
早期阿爾茨海默病新型治療的患者和醫生期望與觀點:醫生調查和患者焦點小組訪談結果 摘要ID#86956 |
Poster viewing time is set from 3:30PM to 4:15PM, during break and lunch time on the date of presentation.
海報查看時間爲演示日期中午和休息時間的下午3:30至4:15。
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.
本發佈討論正在開發中的試劑的研究應用,不旨在傳達關於功效或安全性的結論。不能保證這些試驗性藥物能夠成功完成臨床開發或獲得衛生管理機構的批准。
* 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 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.2
*Protofibrils被認爲對AD導致的腦損傷有貢獻,並被認爲是Aβ的最有毒形式,對與這種進行性的致殘性疾病相關的認知功能下降具有主要作用。1 Protofibrils對腦中的神經元造成損傷,從而可能通過多種機制對認知功能產生負面影響,不僅增加不溶性Aβ腦斑的發展,而且增加直接對腦細胞膜和傳遞神經元之間或神經元與其他細胞之間信號的連接的損傷。人們認爲,減少Protofibrils可以通過減少腦中神經元損傷和認知功能障礙來防止AD的進展。2
Media Inquiries:
Eisai Co., Ltd.
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TEL: +81 (0)3-3817-5120
媒體查詢:
英塞爾製藥株式會社
公共關係部
電話: +81 (0)3-3817-5120
Eisai Inc. (U.S.)
Libby Holman
+1-201-753-1945
[email protected]
英塞爾製藥有限公司(美國)
Libby Holman
+1-201-753-1945
[email protected]
Eisai Europe, Ltd. (UK, Europe, Australia, New Zealand and Russia)
EMEA Communications Department
+44 (0) 786 601 1272
[email protected]
英塞爾製藥歐洲有限公司(英國、歐洲、澳大利亞、新西蘭和俄羅斯)
EMEA通信部
+44 (0) 786 601 1272
[email protected]
[Notes to editors]
[編輯注意事項]
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 in the U.S., Japan, China, South Korea, Hong Kong China and Israel. Eisai has also submitted applications for approval of lecanemab in 12 countries and regions, including the European Union (EU).
LEQEMBI's FDA approval was based on Phase 3 data from Eisai's, global Clarity AD clinical trial, in which it met its primary endpoint and all key secondary endpoints with statistically significant results. The primary endpoint was the global cognitive and functional scale, Clinical Dementia Rating Sum of Boxes (CDR-SB). In the Clarity AD clinical trial, treatment with lecanemab reduced clinical decline on CDR-SB by 27% at 18 months compared to placebo.3,4 The mean CDR-SB score at baseline was approximately 3.2 in both groups. The adjusted least-squares mean change from baseline at 18 months was 1.21 with lecanemab and 1.66 with placebo (difference, −0.45; 95% confidence interval [CI], −0.67 to −0.23; P<0.001). In addition, the secondary endpoint from the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL), which measures information provided by people caring for patients with AD, noted a statistically significant benefit of 37% compared to placebo. The adjusted mean change from baseline at 18 months in the ADCS-MCI-ADL score was −3.5 in the lecanemab group and −5.5 in the placebo group (difference, 2.0; 95% CI, 1.2 to 2.8; P<0.001). The ADCS MCI-ADL assesses the ability of patients to function independently, including being able to dress, feed themselves and participate in community activities. The most common adverse events (>10%) in the lecanemab group were infusion reactions, ARIA-H (combined cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis), ARIA-E (edema/effusion), headache, and fall.
In November 2023, Eisai presented 24-month data from the Phase 3 Clarity AD open Label Extension Study demonstrating that LEQEMBI-treated patients continued to show benefit at 24 months of treatment. In the 18-month core study of Clarity AD, there was a statistically significant difference in global cognition and function as measured by CDR-SB between the LEQEMBI and placebo groups. The separation in CDR-SB between the group that continued to receive LEQEMBI (early start group) and the group who switched from placebo to LEQEMBI (delayed start group) was maintained during the 6-month OLE following the core study. This indicates that similar disease trajectory for both early and delayed start groups occurred with LEQEMBI administration. The blood biomarker results (plasma Aβ42/40 ratio, ptau181, GFAP and NfL) showed improvement even after delayed initiation of treatment with LEQEMBI.
These results suggest that LEQEMBI treatment may affect clinical outcomes through improvement of AD pathology. 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 E2814
An investigational anti-microtubule binding region (MTBR) tau antibody, E2814, is being developed as a disease-modifying agent for tauopathies including sporadic AD. Phase I clinical studies are underway. E2814 was discovered as part of the research collaboration between Eisai and University College London. E2814 is designed to prevent the spreading of tau seeds within the brains of affected individuals. In addition, a Phase II/III Tau NexGen study for the treatment of dominantly inherited Alzheimer's disease (DIAD), conducted by the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) led by Washington University School of Medicine in St. Louis (St. Louis, MO, USA), is underway.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.About E2025
E2025 is Eisai's in-house discovered and developed investigational novel anti-EphA4 (Erythropoietin-producing hepatocellular receptor A4) antibody that enhances EphA4 cleavage. E2025 could potentially promote synaptic remodeling of glutamic neurons. A Phase 1 study for E2025 is underway.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.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 lecanemab for the treatment of AD pursuant to an agreement with BioArctic in December 2007. The development and commercialization agreement on the antibody lecanemab back-up was signed in May 2015.
關於Lecanemab(LEQEMBI),
Lecanemab是英塞爾與BioArctic戰略研究聯盟的結果。它是一個人源化的免疫球蛋白G1(IgG1)單克隆抗體,對集聚的可溶式(Protofibril)和不溶性的澱粉樣蛋白β(Aβ)有指向性。Lecanemab已獲得美國、日本、中國、韓國、中國香港和以色列的批准。英塞爾還提交了12個國家和地區批准LEQEMBI的申請,包括歐洲聯盟(EU)。
LEQEMBI的FDA批准基於英塞爾全球Clarity AD臨床試驗的三期數據,該數據符合其主要終點和所有關鍵次要終點,結果具有統計學顯著性。主要終點是全球認知和功能量表,臨床癡呆評分盒和C(CDR-SB),在Clarity AD臨床試驗中,Lecanemab治療在18個月內將CDR-Sb的臨床下降降低了27%,與安慰劑相比。3,4基線時的平均CDR-Sb分數在兩組中均約爲3.2。在18個月時從基線調整最小二乘平均變化爲1.21(Lecanemab)和1.66(安慰劑),調整差異(-0.45;95%置信區間[CI],-0.67至-0.23;P 10%)是輸注反應、ARIA-H(合併於腦微出血,腦宏出血和淺表性色素沉着症),ARIA-E(水腫/滲出),頭痛和跌倒。
2023年11月,Eisai公司公佈了第三階段Clarity AD延續性研究24個月數據,證明接受LEQEMBI治療的患者在治療24個月後仍然表現出益處。在Clarity AD的18個月核心研究中,LEQEMBI組與安慰劑組之間的CDR-Sb全球認知和功能存在統計學差異。在覈心研究後跟隨的6個月OLE中,延遲開始組(安慰劑轉LEQEMBI組)和早期開始組(LEQEMBI組)之間的CDR-Sb分離保持不變,表明LEQEMBI治療下發病發展軌跡相似。血液生物標誌物結果(血漿Aβ42/40比值,ptau181,GFAP和NfL)顯示,即使LEQEMBI治療延遲開始,也能得到改善。
這些結果表明,LEQEMBI治療可能通過改善AD病理影響臨床結果。自2020年7月以來,面向患有臨床正常且腦中澱粉樣蛋白中間或升高水平的人群的第三階段臨床研究(AHEAD 3-45)正在進行。AHEAD 3-45是由美國阿爾茨海默病臨床試驗聯盟作爲公共-私人合作伙伴關係進行的,該聯盟提供了美國AD和相關癡呆症學術臨床試驗的基礎設施,由美國國家老齡化研究所和Eisai和Biogen資助。自2022年1月以來,主導華盛頓大學醫學院DIAN-TU的顯性遺傳AD(DIAD)的Tau NexGen臨床研究正在進行中,其中包括lecanemab作爲骨幹抗澱粉樣蛋白治療。E2814是一種正在研發的抗微管結合區(MTBR)tau抗體,作爲針對包括散發性AD在內的tau病理的疾病修飾劑。一期臨床研究正在進行中。E2814是Eisai和倫敦大學學院合作研究的一部分,旨在防止在受影響的人腦中tau種子的擴散。此外,由St. Louis華盛頓大學醫學院(St. Louis,MO,美國)領導的顯性遺傳性阿爾茨海默病(DIAD)的II/III期Tau NexGen研究正在進行中,該研究包括lecanemab作爲骨幹抗澱粉樣蛋白療法。
E2814相關簡介E2511是Eisai內部發現並研製的一種新型分子,可直接結合於神經細胞膜上的一種神經生長因子(NGF)所在的肌動蛋白受體激酶A(TrkA)。E2511有可能促進損傷乙酰膽鹼能神經元的恢復和突觸重塑。一期研究正在進行中。
E2511相關簡介E2025是Eisai內部發現並研製的一種新型抗EphA4(紅細胞生成肝細胞A4)抗體,可促進EphA4的裂解。E2025有可能促進穀氨酸能神經元的突觸重塑。一期研究正在進行中。
E2025相關簡介Eisai和Biogen自2014年以來一直在合作開發和推廣AD治療。Eisai在全球範圍內負責lecanemab的開發和監管提交,並與Biogen一起共同推廣產品,Eisai擁有最終決策權。
Eisai和BioArctic自2005年以來一直在長期合作開發和推廣AD治療。Eisai與BioArctic於2007年12月簽訂協議,獲得了研究、開發、生產和銷售lecanemab治療AD的全球權利。2015年5月,雙方簽訂了有關抗體lecanemab備份的開發和商業化協議。《自然通訊》2021年6月發表:Aβ受體專門識別纖維末端和神經毒性寡聚體所顯示的分子特徵。 DOI:10.1038/s41467-021-23507-z;《國際分子科學》2020年2月發表:Amyloid-β原纖維是阿爾茨海默病治療的重要靶點。DOI:10.3390/ijms21030952。 PMID:32023927;PMCID:PMC7037706。
Eisai在阿爾茨海默病治療上與BioArctic長期合作自2005年以來合作。Eisai已在2007年12月與BioArctic簽訂了協議,獲得了研究、開發、生產和銷售lecanemab治療AD的全球權利。2015年5月,雙方簽訂了有關抗體lecanemab備份的開發和商業化協議。
References
參考文獻
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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:
van Dyck, H., et al. Lecanemab in Early Alzheimer's Disease. New England Journal of Medicine. 2023;388:9-21. .
阿密因L,賀錦麗DA。Aβ受體專門識別纖維末端和神經毒性寡聚體。《自然通訊》Patent:2021年6月;12: 3451. DOI: 10.1038/s41467-021-23507-z。
小野幸雄、辻美蘭。Amyloid-β原纖維是阿爾茨海默病治療的重要靶點。《國際分子科學》 2020 年 2 月;21(3):952。 doi:10.3390/ijms21030952。 PMID: 32023927;PMCID: PMC7037706。
Eisai在臨床阿爾茨海默病試驗(CTAD)會議上展示了lecanemab第三階段確認性Clarity AD研究的全部結果。請參閱:
van Dyck H.,等。初期階段的阿爾茨海默病lecanemab。新英格蘭醫學雜誌。2023年;388:9-21。
SOURCE Eisai Inc.
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