A Double-Blind, Placebo-Controlled, Double-Dummy Study of Donanemab and RG6289 in PSEN1 E280A Mutation Carriers, and in Non-Randomized, Placebo-Treated Non-Carriers From the Same Kindred, to Evaluate the Efficacy and Safety of Donanemab, RG6289, or the Combination of Donanemab and RG6289, in the Treatment of Autosomal-Dominant Alzheimer's Disease

The study will be conducted in 2 blinded parts (Part 1 and Part 2). In Part 1, study participants who are mutation carriers will receive active donanemab and non-mutation carriers will receive placebo-donanemab for up to 18 months (76 weeks), with a minimum treatment period of 9 months. Amyloid PET scans will be conducted at screening, 9, and 18 months in Part 1. Participants who are at or below 11 CL at screening or reach complete amyloid plaque clearance as measured by florbetapir F18 PET (defined as ≤11 CL) at 9 months will initiate Part 2. Participants who are ≤11 CL at screening may delay their entry into Part 2 for up to 6 months at the discretion of the Investigator. All remaining participants will start Part 2 after completing 18 months (76 weeks) in Part 1 independent of amyloid results. Non-carriers will receive placebo in both Parts 1 and 2.
In Part 2, study participants who are mutation carriers will be randomized 1:1:1:1 in a full factorial design to receive either RG6289 + placebo-donanemab (RG6289 alone group), donanemab + placebo-RG6289 (donanemab alone group), the combination of RG6289 and donanemab (combination group), or placebo-RG6289 and placebo-donanemab (placebo group). All non-carriers will be assigned to the placebo group. CDR-GS at the end of Part 1 and the amyloid level using the last completed amyloid PET scan in Part 1 will be used for stratification. All study participants will participate in a double-dummy design for the duration of Part 2 receiving both an intravenous (IV) infusion at the required interval for the donanemab or matching placebo as well as a daily oral treatment of RG6289 or matching placebo.
An exploratory outcome of Part 1 is a comparison of the amyloid clearance between this ADAD cohort and historical controls using propensity score matching. The primary outcome in Part 2 is change from the start of Part 2 through the end of Part 2 in brain amyloid load in PSEN1 E280A mutation carriers as measured by amyloid PET imaging. Other endpoints will include fluid and imaging biomarkers and measures of cognition and functioning. The maximum study duration for any individual participant will be 3 years, not including the screening or follow-up periods

开始日期2026-01-15

申办/合作机构

Banner Health

[+2]

NCT06911944

/ Not yet recruiting临床4期IIT

A Randomized, Double-Blind, Placebo-Controlled, Phase 4 Dose-Escalation Study Evaluating the Safety, Tolerability, and Efficacy of Donanemab in Adults With Down Syndrome

The goal of this clinical trial is to learn if donanemab can reduce levels of amyloid in the brain, and if donanemab is safe and well-tolerated in participants with Down syndrome.
The main questions it aims to answer are: Does donanemab reduce amyloid in the brain? Is donanemab safe and well-tolerated in people with Down syndrome? Researchers will compare donanemab to a placebo (a look-alike substance that contains no drug) to see if donanemab works to reduce levels of amyloid in the brain.
Participants in the study will be 35-50 years old and will be in the study for 12 months. Participants will then stay in the study for an additional 12 months in an long-term extension where all participants will receive donanemab. Participants who had a reduction in amyloid (measured by amyloid brain scan) by the end of the first 12 months will receive placebo for the long-term extension, while participants who did not have an amyloid reduction will receive study donanemab for the long-term extension. Everyone (participants and study staff) will remain blinded to treatment for the duration of the study.
Participants will:
* Have intravenous (IV) infusions of donanemab (or placebo) every 4 weeks
* Visit the clinic once every other month for checkups and tests. These tests will include brain scans (magnetic resonance imaging [MRI] and positron emission tomography [PET] ), blood draws and memory tests.
* Have a study partner who who can provide information about the participant and can join participant for some of the study visits.

开始日期2025-12-01

申办/合作机构

University of Southern California

[+3]

NCT06566170

/ RecruitingN/A

Long-Term Real-World Comparative Effectiveness of Donanemab Plus Usual Care Versus Usual Care Alone in US Patients With Early Symptomatic Alzheimer's Disease (TRAILBLAZER-REAL US)

The main purpose of this study is to evaluate the long-term effectiveness of donanemab plus usual care versus usual care alone in participants with early symptomatic AD. The study will employ a prospective, observational cohort design with participant management resembling real-world practice to the greatest extent possible via prospective assessments and linkage to historical and prospective electronic health records. The study will last about 273 weeks and may include up to 28 visits.

开始日期2024-10-07

申办/合作机构

Eli Lilly & Co.

100 项与多奈单抗相关的临床结果

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100 项与多奈单抗相关的转化医学

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100 项与多奈单抗相关的专利（医药）

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243

项与多奈单抗相关的文献（医药）

2026-02-01·Neural Regeneration Research

Recent advances in immunotherapy targeting amyloid-beta and tauopathies in Alzheimer’s disease

Article

作者: Guo, Wanshu ; Sha, Sha ; Ren, Lina ; Qu, Le ; Li, Ying ; Cao, Yunpeng ; Wang, Yan ; Xing, Xiaona

Alzheimer’s disease, a devastating neurodegenerative disorder, is characterized by progressive cognitive decline, primarily due to amyloid-beta protein deposition and tau protein phosphorylation. Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer’s disease. Conventional drugs, such as donepezil, can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline. Currently, active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer’s disease and other transgenic animal models, attracting considerable attention. However, the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab. This review first discusses the advancements in the pathogenesis of Alzheimer’s disease and active and passive immunotherapies targeting amyloid-beta and tau proteins. Furthermore, it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects. Although some antibodies have shown promise in patients with mild Alzheimer’s disease, substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer’s disease.

2025-11-01·JPAD-Journal of Prevention of Alzheimers Disease

Early Alzheimer’s disease (mild cognitive impairment or mild dementia): Prevalence, diagnostics, treatment options, and guidelines in Asia, Australasia, and Pacific nations countries

Review

作者: Shea, Yat Fung ; Park, Kee Hyung ; Tan, Lolita Stephanie ; Prusty, Vinay ; Hsu, Jung-Lung ; Panegyres, Peter K ; Eom, Young In ; Huang, Yao Hsien

Early diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD) with mild dementia is becoming increasingly important to enable patients to receive appropriate treatment with available amyloid-targeting therapies. Reviews of AD prevalence and diagnostic and treatment patterns typically focus on global or western populations, but the situation in Asia, Australasia, and Pacific Nations (AAPN) countries is less clear. We performed a narrative review of literature for AD in several AAPN countries, focusing on patients with MCI or mild dementia who may benefit from early treatment. Published information regarding AD incidence and prevalence and current practice in AAPN countries is limited and the nature of available information differs between countries. However, AAPN countries include some of the most rapidly aging populations and show the associated increasing trend of all-cause dementia prevalence observed globally. Although lecanemab and donanemab are now approved for AD with MCI and mild dementia in several AAPN countries, the most appropriate diagnostic pathway for patients with MCI and early AD is not established. Even though the AAPN region includes countries with routine access to advanced technologies, concerns have already been raised about the ability of healthcare systems in Australia, New Zealand, and Korea to respond to approvals of new AD therapies, including the need to ensure availability of biomarker testing and dementia specialists to allow patients to receive the early diagnosis required to enable appropriate treatment. Guidelines and national policies also need updating to differentiate between dementia subtypes and include amyloid-targeting therapies for eligible patients with early AD.

2025-11-01·EUROPEAN JOURNAL OF PHARMACOLOGY

Mapping the evolving landscape of lecanemab research in Alzheimer's Disease: A bibliometric analysis

Article

作者: Xu, Dingwen ; Shen, Jiaxing ; Ma, Ruijia ; Zhao, Xu ; Yang, Zhe

BACKGROUND:

Lecanemab, a monoclonal antibody that targets amyloid-beta aggregates, has emerged as a promising therapeutic for Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder characterized by cognitive decline and amyloid pathology. Research on the use of lecanemab in treating AD has increased; however, no relevant bibliometric analyses have been conducted. To address this gap, this study employed bibliometric methods to search for the relevant literature and analyze research trends investigating AD and lecanemab.

METHODS:

We performed a literature search of the Web of Science core database for studies investigating AD and lecanemab, published from database inception up to April 3rd, 2025. After rigorous screening, Excel, VOSviewer, and CiteSpace were used to perform a bibliometric analysis of publications, citations, and collaboration networks among countries, institutions, and authors, along with cluster and burst analyses of keywords. Coremine was used for text mining entries significantly related to AD and lecanemab.

RESULTS:

The number of studies published on AD and lecanemab has increased annually. The countries with the highest publication output were the United States, the United Kingdom, and China. The leading institutions that produced the most articles were Eisai Inc. (Bunkyo City, Tokyo, Japan), Uppsala University (Uppsala, Sweden), and Harvard Medical School (Boston, MA, USA). The top three authors were Lars Lannfelt, Shobha Dhadda, and Michio Kanekiyo. The most prolific journals included The Journal of Alzheimer's Disease, Alzheimer's and Dementia, and Ageing Research Reviews. The most cited article was "Lecanemab in Early Alzheimer's Disease," by Van Dyck et al., published in The New England Journal of Medicine in 2023, which has accrued 172 citations. The 10 most frequently occurring keywords were Alzheimer's disease, lecanemab, dementia, aducanumab, amyloid-beta, immunotherapy, tau, a-beta, mouse model, and donanemab. Text mining revealed that drugs, anatomical structures, chemical molecules, genes, diseases, and procedures were significantly associated with both AD and lecanemab.

CONCLUSION:

The bibliometric and text mining analysis revealed trends in research investigating the correlation between lecanemab and AD. It analyzed the cooperation among countries, regions, and authors, highlighting recent research hotspots. These data offer objective insights for scientific research and clinical practice on lecanemab and AD. These findings provide a roadmap for prioritizing clinical trials, optimizing drug development strategies, and addressing knowledge gaps in amyloid-targeted therapies.

1,162

项与多奈单抗相关的新闻（医药）

2025-10-28

·生物谷

70% 患者漏诊？别等“认不出家人” 再后悔！一文读懂阿尔兹海默病现状、科研竞速与千亿市场蓝图

本文将深入剖析全球与中国的AD疾病负担，盘点最前沿的研究进展，描绘产业发展图谱并解读关键政策，为您全面展现这场人类与遗忘之战的现状与未来。阿尔兹海默病（AD，Alzheimer‘s Disease,）这场悄然席卷全球的“记忆风暴”，已成为本世纪人类健康面临的最大挑战之一，其不仅仅剥夺了数百万患者的记忆与尊严，更为其家庭和社会带来了难以承受的照护与经济负担。在过去的二十余年里，针对阿尔兹海默病的新药研发屡战屡败，科学界一度被悲观情绪笼罩，然而随着近年来Aβ抗体药物的获批、血液生物标志物检测的突破及中国在相关政策上的强力引导，如今，我们正站在一个历史的转折点上。本文将深入剖析全球与中国的AD疾病负担，盘点最前沿的研究进展，描绘产业发展图谱并解读关键政策，为您全面展现这场人类与遗忘之战的现状与未来。图片来源：thebluediamondgallery.com （一）全球疾病负担根据国际阿尔茨海默病协会（ADI）《2023 年世界阿尔茨海默病报告》，全球目前有超过 5500 万痴呆症患者，其中约 60%-70% 为阿尔茨海默病患者。这一数字正随全球人口老龄化急剧攀升 ——2024 年最新流行病学数据预测，到 2050 年全球痴呆症患者总数将高达1.52 亿，AD 已不仅是单纯的健康问题，更演变为严峻的社会经济课题。从经济成本来看，ADI 报告估算 2023 年全球与痴呆症相关的社会总成本（含直接医疗费用、直接社会护理费用及非正式护理成本）已飙升至1.3 万亿美元；若不采取有效干预措施，2030 年这一数字将增至 1.7 万亿美元。更值得关注的是，疾病负担正快速向中低收入国家转移：这些国家医疗卫生系统准备不足、照护资源匮乏，未来将面临更严峻的挑战。（二）中国面临的严峻挑战作为全球人口最多、老龄化速度最快的国家之一，中国正承受着 AD 带来的巨大压力，且呈现出 “基数大、增速快、诊疗照护短板突出” 的特点： 1. 患者规模居全球首位：据 2023 年《Global Times》报道，中国 60 岁以上痴呆患者共 1507 万，其中 AD 患者约983 万，占全球 AD 患者总数的近五分之一，是全球 AD 患者数量最多的国家。 2. 增速与年轻化趋势：研究预测，到 2030 年中国 AD 患者将达 1600 万，2050 年将突破 4000 万，平均每年新增近百万患者；更需警惕的是，中国 AD 患者中21.3% 年龄低于 60 岁，显著高于国际 5%-10% 的比例，且女性患病率为男性的 1.8 倍，死亡人数也更高。 3. 诊疗与照护短板突出：与庞大患者基数形成鲜明对比的是，中国 AD 诊出率仅约 30%，意味着近 700 万患者尚未被确诊、游离于正规医疗系统之外。背后原因包括公众将早期症状误认为 “自然衰老”、病耻感较强，以及基层医疗机构认知障碍诊疗能力薄弱。照护端压力更甚：超过 90% 的患者由家庭成员（配偶、子女）居家照护，长期照护带来的精神压力、身体疲惫及经济支出，导致许多照护者自身陷入身心健康危机；而专业照护机构 “一床难求”、费用高昂，多数家庭难以负担。图片来源：openaccessgovernment.org 二、科研进展篇——打破Aβ僵局，迈向精准诊疗新时代（一）治疗领域：迟来二十年的“破冰” 2023年是阿尔兹海默病治疗史上具有里程碑意义的一年，经过数十年屡败屡战的探索，针对β淀粉样蛋白（Aβ）假说的靶向治疗终于取得了确凿的临床验证。首先是由渤健（Biogen）和卫材（Eisai）联合开发的仑卡奈单抗（Lecanemab）获得了FDA的完全批准，其大型III期临床试验（Clarity AD）结果显示，相较于安慰剂，仑卡奈单抗能在18个月内将早期AD患者的临床痴呆评分总和（CDR-SB）的下降速度延缓27%。紧接着，礼来（Eli Lilly）的多奈单抗（Donanemab）的III期临床试验（TRAILBLAZER-ALZ 2）结果同样令人振奋，其延缓认知功能下降的幅度达到35%，特别是在疾病早期阶段和低至中度 Tau 病理负担的患者中效果更为显著。这两款药物的核心意义在于，其首次明确证实了清除大脑中的Aβ斑块能够为患者带来具有临床意义的获益，实现了从“对症治疗”到“针对核心病理的疾病修饰治疗” 的关键跨越。当然，科学界也保持着审慎的乐观。这两种药物都存在需要密切关注的风险，即淀粉样蛋白相关影像学异常（ARIA），主要表现为脑水肿（ARIA-E）或微出血（ARIA-H）。尽管大多数情况下无症状且可管理，但这要求在使用过程中进行严格的患者筛选和用药后监测。目前，中国的研发力量也在快速跟进。除了此前条件获批上市的GV-971（甘露特钠胶囊）所引发的、关于其作用机制与临床价值的持续学术讨论外，众多本土生物技术公司和创新药企也布局了Aβ、Tau、神经炎症等热门靶点，一些药物已进入临床早期试验阶段，预示着未来中国在AD创新药领域可能占据一席之地。（二）诊断技术：血液检测开启“早筛革命” 如果说新药获批是治疗领域的“破冰”，那么血液生物标志物检测技术的突破，则是诊断领域的一场“革命”。过去，确诊阿尔兹海默病依赖于脑脊液检测（腰椎穿刺）或正电子发射断层成像（PET），这些方法要么有创，要么价格昂贵（单次PET扫描费用可达万元），且可及性低，难以用于大规模筛查。近年来，科学家们成功实现了通过普通血液样本，高精度检测与AD核心病理相关的生物标志物，比如磷酸化Tau蛋白（p-tau181, p-tau217等）和Aβ42/40比率。多项发表于《美国医学会杂志》（JAMA）、《柳叶刀神经病学》（The Lancet Neurology）等顶级期刊的研究表明，这些血液检测指标的准确度可与脑脊液检测相媲美，甚至能高度预测大脑中Aβ和Tau的沉积情况。这意味着，未来在社区医院或体检中心，通过一次简单的抽血，就有可能高效、无创、低成本地识别出处于AD早期甚至无症状期的潜在患者。这项技术的普及将彻底改变AD的诊疗路径，使“早发现、早诊断、早干预”成为可能，为疾病修饰药物的有效应用打开关键的时间窗口。（三）新兴探索方向：多通路并进的未来除了Aβ和Tau这两大经典通路，科学界对AD复杂机制的理解正在不断深化。 1、大脑-肠道-微生物轴：这一理论揭示了肠道菌群失衡可能通过免疫、代谢和神经炎症途径影响大脑健康，为AD防治提供了新的视角和潜在干预靶点。 2、神经炎症：小胶质细胞等大脑免疫细胞的功能失调被证实与AD进展密切相关，以TREM2为代表的新靶点成为药物研发的新热点。 3、人工智能：AI技术正被广泛应用于AD的早期筛查（如通过语言、行为模式分析）、医学影像（MRI、PET）的自动判读以及疾病进展预测模型的构建，助力精准医疗。图片来源：openaccessgovernment.org 三、产业篇——从诊断到照护，产业链条正在形成（一）治疗药物市场：百亿美元赛道的开启仑卡奈单抗和多奈单抗的成功催生了一个潜力巨大的治疗药物市场。有分析师预测，这两款药物的年销售峰值均有望突破100亿美元，其不仅为渤健/卫材和礼来带来了先发优势，也极大地提振了整个神经科学领域的研发信心。中国市场同样蕴含着巨大机遇。随着国家药监局（NMPA）对创新药审评审批的加速，以及国内患者对有效疗法日益增长的需求，国际药企正积极推动其AD新药在中国上市。与此同时，国内药企也在加速布局，一方面瞄准生物类似药的开发，另一方面则在积极寻找具有差异化优势的新靶点药物，力求在未来竞争激烈的市场中占据一席之地。（二）诊断市场崛起：IVD企业的下一个黄金赛道血液生物标志物检测技术的成熟为体外诊断（IVD）行业开辟了一个全新的、规模可达百亿级的蓝海市场；全球诊断巨头，比如罗氏（Roche）、雅培（Abbott）、奎斯特诊断（Quest Diagnostics）等均已投入重金开发相关的检测试剂盒和分析平台。在中国，包括深圳华大基因、北京热景生物、上海科华生物等在内的多家IVD上市公司和初创企业，也纷纷宣布在此领域取得技术进展，一旦相关产品获批上市并逐步被纳入医疗机构检测目录及医保支付范围，AD血液检测有望像如今的血糖、血脂检测一样普及，其市场潜力不可估量，这不仅是商业机会，更是提升我国AD整体诊疗水平的关键基础设施。（三）数字疗法与智能照护：“银发经济”的科技赋能在药物和诊断之外，一个以科技驱动的数字健康和智能照护产业正在迅速崛起。 1、数字疗法：基于手机或平板电脑的认知训练软件和游戏被用于轻度认知障碍（MCI）和早期AD患者的认知功能维护与康复，部分产品已获得监管机构的批准作为医疗器械。 2、智能可穿戴设备：具备GPS定位、心率监测、跌倒检测等功能的手表、手环能有效保障患者安全，减轻照护者防止患者走失的焦虑。 3、智能家居与机器人：通过环境传感器监测患者日常活动规律，在异常时报警；辅助机器人则可以帮助完成简单的物品递送、提醒服药等任务，从物理上减轻照护负担。这些技术与服务，共同构成了“银发经济”中极具活力的细分市场，为解决AD带来的照护难题提供了多元化的解决方案。（四）专业照护服务产业：需求巨大但供给不足的痛点面对数千万的失智老人，专业照护服务的需求如饥似渴。专门为认知症老人设计的“记忆照护中心”、提供专业失智护理服务的养老机构，在一线城市已是“一床难求”。然而，这个行业面临着专业人才（如认知症照护师）极度短缺、运营成本高、收费标准与普通家庭支付能力存在差距等诸多挑战。如何建立可持续的商业模式，扩大优质供给，是摆在产业和社会面前的一道难题。图片来源：Journalist's Resource 四、政策篇——国家战略下的系统性应对（一）顶层设计中国政府对老龄化带来的 AD 挑战早有布局：“健康中国 2030” 规划纲要明确将 “维护老年健康、加强慢性病综合防控” 列为核心内容；2025 年 1 月，国家卫健委等 15 部门联合发布《应对老年期痴呆国家行动计划（2024-2030 年）》，首次以 “国家行动计划” 形式明确 AD 防治路径，包括将认知功能筛查纳入基本公共卫生服务、扩大长期照护保险试点、加强专业照护人才培养等，为全社会应对 AD 提供了清晰指引。（二）药物审评与医保政策国家药监局（NMPA）近年对 AD 创新药持开放态度：通过 “优先审评审批”“突破性治疗药物” 等通道，加速仑卡奈单抗、多奈单抗等药物在华上市，让中国患者同步享受全球科研成果。但创新药的 “可及性” 最终取决于支付端：年治疗费数十万元的药物，对基本医保基金和个人均构成压力。未来，国家医保目录动态调整、商业健康保险补充（如 “惠民保” 纳入 AD 治疗），将成为平衡 “创新激励” 与 “基金可持续性” 的关键。（三）公共卫生与长期照护保险：构建系统性防线推动将老年人认知功能筛查纳入国家基本公共卫生服务项目是实现早发现、早干预的核心举措，目前已在部分城市和地区开展试点，未来有望在全国范围内推广。更为深远的是长期照护保险制度的探索。自2016年起，我国已在数十个城市试点建立长期护理保险，旨在为失能（包括因AD导致的失智）人员的基本生活照料和医疗护理提供费用或服务保障，这项制度的完善与推广将从根本上有望解决AD患者及其家庭面临的照护费用难题，是应对AD社会负担的长期性、系统性解决方案。图片来源：calhealthreport.org 五、挑战与展望（一）核心挑战：横亘在前的多重障碍尽管前景光明，但前路依然布满荆棘。 1、可及性与支付难题：创新疗法的高成本是其普及的最大障碍，如何通过医保谈判、商保创新、企业患者援助计划等多方共付模式，让更多患者用得上、用得起，是亟待解决的现实问题。 2、诊疗体系不完善：基层医疗机构对AD的识别和规范管理能力不足，大医院与社区之间的双向转诊渠道不畅，导致患者就医体验差，诊疗连续性被打断。 3、社会认知与病耻感：公众对AD的科学认知仍需提高，“老糊涂不是病”的观念依然普遍，病耻感导致很多家庭不愿公开面对，延误了最佳干预时机。 4、照护资源短缺与质量不均：专业照护人员和机构数量远远跟不上需求，且服务质量参差不齐，缺乏统一的行业标准和有效监管。图片来源：tasnimnews.com 六、未来展望面对挑战，我们更应看到未来的方向和希望。（一）早诊早治成为共识：随着血液检测技术的普及，AD的诊疗关口将大幅前移，预防性干预和早期治疗将成为主流。（二）联合治疗是趋势：如同治疗艾滋病和癌症一样，未来AD的治疗很可能是针对Aβ、Tau、神经炎症等多靶点的“鸡尾酒”式联合疗法，以实现最佳疗效。（三）中国市场的独特性与机遇：中国庞大的患者基数和快速发展的数字化生态（如移动支付、远程医疗、人工智能），为开发具有中国特色的、可负担的早筛模式、数字疗法和社区-居家照护解决方案提供了独特土壤。（四）全社会的共同行动：战胜AD，绝非仅靠医药界所能完成。它需要政府、产业界、医疗机构、科研机构、社区以及每一个家庭的通力协作。从公众教育、早期筛查、规范诊疗到专业照护和社会支持，我们需要共同构建一个理解、尊重和支持认知障碍患者的“痴呆友好型社会”。七、小结阿尔茨海默病的战役依然艰巨，但希望的曙光已清晰可见：科研上，Aβ 抗体药物与血液检测技术的突破，为患者带来了 “对因治疗” 与 “早期发现” 的可能；产业上，涵盖医药、诊断、数字健康、专业照护的生态正在加速成型；政策上，中国的 “国家行动计划” 为防治提供了系统性保障。这场与 “遗忘” 的赛跑，关乎数千万人的福祉，任何单一力量都难以取胜。唯有坚持 “协同创新、系统应对”，才能为人类赢得更多主动权，让每一位老人都能 “有尊严地记忆”。（生物谷Bioon.com）

2025-10-27

·FiercePharma

Are We Nearing a Tipping Point in Alzheimer’s Disease?

None Alfred W. Sandrock, Jr., M.D., Ph.D.Chief Executive Officer of Voyager TherapeuticsAs the annual Clinical Trials on Alzheimer’s Disease (CTAD) conference approaches, new data on emerging targets such as tau and advanced delivery methods are converging.Researchers in the field of Alzheimer’s Disease (AD) are not known for optimism. We had decades with precious little to be optimistic about; decades in which one seemingly promising drug after another failed.Recently, the momentum in AD has begun to shift. We now have two FDA-approved drugs, lecanemab (Leqembi) and donanemab (Kisunla), shown to slow disease progression and cognitive and functional decline in some patients. Both drugs are anti-amyloid antibodies, and critics note that they are only about 30% effective. I would remind those critics that early drugs for multiple sclerosis were also only about 30% effective, while today’s MS drugs hit 60-70%; you have to start somewhere. In AD and neurodegenerative diseases in general, what has been particularly exciting is the speed at which human genetics and advances in brain imaging are helping us understand the molecular underpinnings of the disease – enabling us to know not only what to target, but how to reach it and how to measure the impact. Case in point is the explosion of interest around tau.The Emergence of Tau: the bullet causing neurodegeneration in ADWhile amyloid dominated AD research for decades, tau is emerging as the next critical target. Recent data have shown that the spread of pathological forms of tau protein in the brain is more closely correlated with the progression of dementia than amyloid. Increasing deposits of amyloid seem to cause tau to spread, and that spread of tau causes neurodegeneration. I often think of amyloid as the trigger, but tau as the bullet.Some of the most encouraging data on targeting tau to-date have come from Biogen’s BIIB080, an antisense oligonucleotide that, in an early clinical trial, robustly lowered tau burden as shown by tau PET imaging and resulted in favorable trends on cognition and function. Then at CTAD 2024, UCB made tau history by establishing with bepranemab that an antibody can inhibit the spread of pathological tau in the brain and slow cognitive decline – though the trial ultimately missed its primary endpoint on functional improvement.Large Phase II trials on Biogen’s BIIB080 and Johnson & Johnson’s anti-tau antibody posdinemab are expected next year. But in the interim, data on several other tau targeting programs are slated for presentation at CTAD this December, including Novartis’s NIO752, UCB’s bepranemab, Bristol Myers Squibb’s BMS-986446, Adel’s ADEL-Y01, and Voyager’s own VY7523. The Voyager team will continue to learn from the field as we complete our clinical trial of our anti-tau antibody VY7523, for which we expect tau PET imaging data next year, and prepare to move our tau silencing gene therapy VY1706 into the clinic next year.Brain-Targeted Delivery: The Key to Unlock AD Treatments?As exciting as the approved anti-amyloid and emerging anti-tau antibodies are, the hard truth remains that antibodies don’t get into the brain particularly well: on average only about 0.1% to 0.5% of the antibody gets into the brain. Fortunately, antibodies are so potent that this miniscule amount is enough to make a therapeutic difference – but no one can call it efficient.Delivery to the brain has long been the white whale of neurology drug development: the blood-brain barrier keeps out most large molecule drugs. Improving delivery could increase efficacy through improved brain targeting, enhance safety by reducing peripheral exposure, and potentially lower costs by reducing required doses.At Voyager we, and companies across the industry, are prioritizing delivery platforms to unlock the therapeutic potential of multiple modalities in neurological diseases. Voyager’s TRACER™ AAV capsids are designed to enable gene therapies for neurological diseases by providing high brain penetration following intravenous dosing. We are using this delivery approach for VY1706, our tau silencing gene therapy, as well as for an APOE gene therapy program for AD and multiple other neurology programs.Another emerging area of interest in brain-targeted delivery is “shuttles,” which leverage receptors on the blood-brain barrier to carry large molecules across it. At CTAD, Roche will share data on trontinemab, a shuttled anti-amyloid antibody. Unshuttled, the antibody (gantenerumab) worked in fewer than 30% of patients and had about a 30% rate of a dangerous side effect, ARIA-E. Trontinemab, which uses a transferrin receptor shuttle to target the antibody to the brain, has shown effectiveness in 91% of patients and reduced ARIA-E to below 5%. Recently Voyager unveiled initial data with our Voyager NeuroShuttle™, which builds on first-generation transferrin receptor shuttles by leveraging a different receptor, ALPL, which has been integral in our gene therapy work. Initial preclinical data showed a distinct pharmacokinetic profile, with brain uptake sustained for greater than 3 weeks post-dose, versus less than one week for transferrin shuttles.More Voyager NeuroShuttle data are on the way – though not in time for CTAD 2025. Even so, the data emerging across the industry on tau-targeted therapies, biomarkers, and next-generation delivery platforms give me optimism – a rare gift for an AD researcher.

基因疗法寡核苷酸临床2期

2025-10-27

·新浪医药

120亿美元！诺华收购RNA疗法新锐

2025年10月26日，诺华正式官宣，将以120亿美元现金收购美国RNA疗法创新企业Avidity Biosciences。此次交易聚焦晚期神经科学管线强化，推进诺华xRNA战略布局，有望在2030年前催生多款新药上市，抢占数十亿美元规模的罕见病治疗市场。 Avidity Biosciences总部位于美国圣地亚哥，其核心竞争力在于独创的抗体-寡核苷酸偶联物（AOCs™）技术平台。该平台创新性地将单克隆抗体的组织特异性与寡核苷酸的精准作用机制相结合，成功解决了传统RNA疗法难以靶向抵达肌肉组织的技术瓶颈，为神经肌肉疾病治疗提供了全新解决方案。交易关键细节全解析估值与对价：Avidity普通股股东每股将获得72美元现金，较10月24日收盘价溢价46%。交易完全稀释估值约120亿美元，预计交割时企业价值约110亿美元。业务拆分安排：交割前，Avidity将把早期精准心脏病学项目拆分至新公司SpinCo。股东每持有10股Avidity股票，可获配1股SpinCo股票，或按比例获取SpinCo资产/股权出售的现金收益。交割条件与时间：交易需满足SpinCo拆分完成、监管机构批准及Avidity股东同意等惯例条件，预计2026年上半年正式交割。交割前，两家公司将保持独立运营。业绩影响：收购完成后，诺华2024-2029年预期销售额复合年增长率（CAGR）将从5%提升至6%，长期有望维持中个位数增长态势。核心管线价值此次收购的核心价值在于Avidity旗下三款处于晚期阶段的疾病修饰疗法，均针对目前无有效治疗手段的罕见神经肌肉遗传病： 1. 1型强直性肌营养不良（DM1）：一种预后极差的进行性疾病，患者缺乏针对性的疾病修饰治疗方案。 2. 面肩肱型肌营养不良（FSHD）：遗传性肌肉疾病，会导致患者肌肉功能持续衰退，最终引发进行性残疾。 3. 杜氏肌营养不良（DMD）：发病年龄早、病情进展迅速，以肌肉进行性损伤为主要特征，严重缩短患者预期寿命。这些候选药物借助AOC平台实现肌肉组织靶向递送，能够直接纠正疾病潜在遗传机制，有望帮助患者恢复肌肉功能并减缓疾病进展。目前，相关药物正推进HARBOR™、FORTITUDE™及EXPLORE44等关键临床试验，距离上市落地迈出重要步伐。近年来，礼来、艾伯维、BMS等大药企纷纷通过合作研发等方式，明确向外界展示了“布局晚期神经科学管线”的战略重点。 AbbVie（艾伯维）2023 年底以 87 亿美元收购 Cerevel，拿下处于 Ⅲ 期的下一代抗精神病药 emraclidine（精神分裂症）和帕金森病 D1/D5 激动剂 tavapadon（Ⅲ 期成功），补强其中枢神经晚期管线。 Eli Lilly（礼来）在 AD 领域拥有已上市单抗 Kisunla，并持续投入帕金森病、疼痛、偏头痛等 Ⅲ 期项目；公司内部已专设 “Lilly Neuroscience” 事业部，系统推进中枢神经晚期管线。 Bristol Myers Squibb（BMS）2023 年底以 140 亿美元收购 Karuna，获得毒蕈碱类抗精神病药 KarXT（精神分裂症 NDA 已获 FDA 受理，另有多项 Ⅲ 期/注册临床进行中）和情绪障碍药物 KAR-2618，快速切入晚期神经精神领域来源:一度医药等加入读者交流群： —精彩回顾— 我国启动全球最大规模尿液HPV筛查研究针对红斑狼疮！阿斯利康首创生物制剂 III 期成功恒瑞乙肝「突破性疗法」来袭 ADC之后，ABC来了全球首例！中国医生体内CAR-T成功治疗狼疮商务合作：杨小雨 15210041717

并购临床3期寡核苷酸信使RNA

100 项与多奈单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11500	多奈单抗	-	-

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
阿尔茨海默病引起的痴呆症	英国	Eli Lilly & Co.	2024-10-23
阿尔茨海默病引起的痴呆症	英国	Eli Lilly Nederland BV	2024-10-23
轻度认知障碍	英国	Eli Lilly Nederland BV	2024-10-23
轻度认知障碍	英国	Eli Lilly & Co.	2024-10-23
阿尔茨海默症	美国	Eli Lilly & Co.	2024-07-02

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
精神障碍	申请上市	加拿大	Eli Lilly Canada, Inc.	-
神经认知障碍	临床3期	中国	Eli Lilly & Co.	2022-10-10
神经认知障碍	临床3期	阿根廷	Eli Lilly & Co.	2022-10-10
神经认知障碍	临床3期	澳大利亚	Eli Lilly & Co.	2022-10-10
神经认知障碍	临床3期	波兰	Eli Lilly & Co.	2022-10-10
神经认知障碍	临床3期	韩国	Eli Lilly & Co.	2022-10-10
神经认知障碍	临床3期	西班牙	Eli Lilly & Co.	2022-10-10
神经认知障碍	临床3期	中国台湾	Eli Lilly & Co.	2022-10-10
神经认知障碍	临床3期	英国	Eli Lilly & Co.	2022-10-10
认知功能障碍	临床2期	美国	Eli Lilly & Co.	2020-11-23

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04437511 (TRAILBLAZER-ALZ 2, PRNewswire) 人工标引	临床3期	阿尔茨海默症	-	Kisunla	窪醖鬱餘繭壓餘獵糧蓋(簾築壓廠膚鬱廠鬱鹹鬱): Difference = -0.6 更多	积极	2025-07-30
				Neuroimaging Initiative (untreated external cohort)
NCT04437511 \| NCT03367403 (TRAILBLAZER-ALZ and ALZ 2, Pubmed \| JAMA Neurol)	N/A	阿尔茨海默症 APOE ε4 allele number \| amyloid levels	3,030	Donanemab	顧獵鏇觸餘襯憲淵鏇構(構襯遞願積蓋構簾蓋醖) = 餘顧襯鏇齋膚構夢衊構齋鹽鬱鹹廠築壓鬱醖築 (衊襯網襯鹹鹽繭艱構簾 ) 更多	积极	2025-05-01
				Placebo	顧獵鏇觸餘襯憲淵鏇構(構襯遞願積蓋構簾蓋醖) = 鬱網蓋鑰齋憲糧醖繭網齋鹽鬱鹹廠築壓鬱醖築 (衊襯網襯鹹鹽繭艱構簾 ) 更多
NCT05108922 (TRAILBLAZER-ALZ 4, Pubmed \| Alzheimers Dement)	临床3期	阿尔茨海默症 amyloid plaque clearance	148	Donanemab	鹽構憲窪繭構齋鏇顧膚(憲簾艱餘獵鬱窪積鑰夢) = 構窪蓋獵鹽蓋鏇壓積鬱餘獵積網積艱鑰齋構製 (襯鏇獵構鹹網齋遞積製 ) 更多	积极	2025-05-01
				Aducanumab	鹽構憲窪繭構齋鏇顧膚(憲簾艱餘獵鬱窪積鑰夢) = 築蓋獵鹽衊遞範衊鑰淵餘獵積網積艱鑰齋構製 (襯鏇獵構鹹網齋遞積製 ) 更多
NCT05738486 (TRAILBLAZER-ALZ 6, Company_Website 1 \| Company_Website 2) 人工标引	临床3期	阿尔茨海默症	843	received two vials (700 mg) of donanemab for the first three infusions, then four vials (1400 mg) thereafterdonanemab for the first three infusions, then four vials (1400 mg) thereafter (Standard Dosing Regimen)	糧積獵淵糧憲壓鬱構鬱(遞製積築憲顧鬱窪鏇鹽) = 獵餘積鹽顧鏇壓築積淵膚觸餘顧築遞獵蓋淵蓋 (願繭簾觸簾艱遞衊鏇遞 ) 更多	积极	2024-10-29
				received 1 vial (350 mg) of donanemab for the first infusion, two vials (700 mg) for the second infusion, three vials (1,050 mg) for the third infusion,donanemab for the first infusion, two vials (700 mg) for the second infusion, three vials (1,050 mg) for the third infusion, and four vials (1400 mg) per infusion thereafter (Modified Titration)	糧積獵淵糧憲壓鬱構鬱(遞製積築憲顧鬱窪鏇鹽) = 網鬱觸範壓獵遞簾膚獵膚觸餘顧築遞獵蓋淵蓋 (願繭簾觸簾艱遞衊鏇遞 ) 更多
NCT01837641 (CTgov)	临床1期	阿尔茨海默症 \| 认知功能障碍 \| 轻度认知障碍	63	Placebo (Placebo IV)	鏇艱鹹憲餘積壓鹹餘顧 = 鏇願構鏇觸齋夢艱醖鹹積艱夢簾夢遞鏇蓋製夢 (夢積範糧構獵壓範觸築, 繭網鑰網齋簾獵艱構膚 ~ 蓋簾蓋艱膚蓋醖構齋鏇) 更多	-	2024-10-04
				LY3002813 (0.1 mg/kg / 0.3 mg/kg LY3002813 IV)	鏇艱鹹憲餘積壓鹹餘顧 = 鬱選夢鏇網鹽鹽壓選醖積艱夢簾夢遞鏇蓋製夢 (夢積範糧構獵壓範觸築, 齋壓鑰網築網醖鹹艱鏇 ~ 蓋繭鬱蓋遞觸壓糧範鹹) 更多
NCT05567159 (CTgov)	临床1期	-	42	Donanemab	艱簾鑰膚選衊積蓋觸範(蓋醖餘鹹簾製蓋夢齋淵) = 窪壓艱餘蓋願鹽鑰獵製糧鹹窪繭糧構鹹觸艱淵 (鬱壓廠襯廠願窪鏇餘網, 23) 更多	-	2024-10-04
NCT05533411 (CTgov)	临床1期	-	36	Placebo (Placebo)	鏇壓鏇憲糧淵製顧窪願 = 夢蓋廠鹽獵壓衊壓築壓範夢夢膚遞鹽淵遞廠築 (蓋壓製鬱壓憲壓膚鬱獵, 壓蓋憲願遞夢簾壓膚鏇 ~ 願積鑰鹹製衊壓製選蓋) 更多	-	2024-10-04
				Donanemab (700 mg Donanemab)	鏇壓鏇憲糧淵製顧窪願 = 壓選壓構襯遞餘製齋壓範夢夢膚遞鹽淵遞廠築 (蓋壓製鬱壓憲壓膚鬱獵, 觸餘範糧構衊築願醖顧 ~ 醖繭鹹襯遞鬱艱窪鹹憲) 更多
NCT04437511 (FDA_CDER) 人工标引	临床3期	阿尔茨海默症	1,736	KISUNLA	獵淵襯醖鑰糧淵淵襯選(壓廠鏇鹽糧餘廠獵艱齋): Difference = 2.92, P-Value = <0.0001 更多	积极	2024-07-02
				Placebo
NCT04437511 \| NCT03367403 (TRAILBLAZER-ALZ \| TRAILBLAZER-ALZ2, AAN2024)	临床2/3期	number of microhemorrhages \| cortical superficial siderosis \| mean arterial pressure ... 更多	2,031	Donanemab	襯鏇糧襯夢遞築顧觸膚(餘願積顧願繭憲願繭糧) = 網衊衊構糧願獵壓繭鏇鑰廠窪膚蓋艱鑰艱鹽網 (積獵鬱齋蓋鹹鬱繭窪襯 )	积极	2024-04-09
NCT05108922 (TRAILBLAZER-ALZ 4, CTgov)	临床3期	阿尔茨海默症 \| 轻度认知障碍	148	Aducanumab (Aducanumab)	選築獵憲蓋鹹選壓蓋願 = 夢選壓網鏇網齋鏇繭繭夢糧觸糧壓網餘餘鏇憲 (廠壓窪淵網糧築窪衊淵, 鏇簾網鬱膚糧觸願網範 ~ 壓願顧糧鏇遞遞淵選鹹) 更多	-	2023-11-02
				Donanemab (Donanemab)	選築獵憲蓋鹹選壓蓋願 = 獵繭艱選衊獵壓膚膚鑰夢糧觸糧壓網餘餘鏇憲 (廠壓窪淵網糧築窪衊淵, 構遞鏇積窪網積蓋窪艱 ~ 繭蓋夢餘夢願淵餘製選) 更多