A phase 1 evaluation of [18F]MK-6240 as a potential PET radioligand for imaging tau protein in the brain of cognitively normal elderly Japanese participants, Japanese patients with mild cognitive impairment and probable mild to moderate Alzheimer's disease

开始日期2019-10-07

申办/合作机构

Cerveau Technologies, Inc.初创企业

JPRN-jRCT2080224887 / Completed临床1期

开始日期2019-10-07

申办/合作机构

Cerveau Technologies, Inc.初创企业

JPRN-JapicCTI-194972 / Completed临床1期

开始日期2019-10-07

申办/合作机构

Cerveau Technologies, Inc.初创企业

100 项与 Cerveau Technologies, Inc. 相关的临床结果

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0 项与 Cerveau Technologies, Inc. 相关的专利（医药）

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项与 Cerveau Technologies, Inc. 相关的文献（医药）

2023-12-01·Alzheimer's & Dementia

Towards a standardized pipeline for tau PET analysis under a GAAIN/LONI and CPAD collaborative framework

作者: Toga, Arthur W. ; Weber, Christopher J. ; Pappas, Ioannis ; Leuzy, Antoine ; Romero, Klaus ; Karten, Yashmin ; Sivakumaran, Sudhir

AbstractBackgroundImaging tau burden in vivo using Positron Emission Tomography (PET) has tremendous potential for advancing our biological understanding of Alzheimer’s disease. Towards this direction, there is a need for post‐acquisition imaging data ‘harmonization’ tools and analysis methods that reduce variance across studies, sites, and scanners, while retaining the power to study complex disease related effects. The Global Alzheimer’s Association Interactive Network (GAAIN), the Laboratory of Neuro Imaging (LONI), and the Critical Path for Alzheimer’s Disease (CPAD) Consortium have undertaken a collaborative effort to provide a harmonized approach to the analysis of tau PET images.MethodThe GAAIN/LONI Pipeline is a software suite that allows the design and execution of neuroimaging workflows through flexible integration of different image preprocessing software and parallel processing via a computer grid. Each workflow has a distinct fingerprint that can be executed locally on different platforms or remotely via GAAIN, thus increasing interoperability and allowing the use of “harmonized” workflows across different datasets. Tau PET workflows were designed and deployed on the GAAIN/LONI Pipeline based on existing literature. In turn, these tau PET workflows were executed on CPAD tau PET to derive tau PET burden. Clinical validation was performed by quantifying tau PET burden on different clinical groups. Analytical validation was performed by correlating the LONI Pipeline results with independently developed pipelines.ResultWe first show feasibility results as the tau PET workflows are deployed and executed on CPAD data. For clinical validation, we tested whether derived metrics can distinguish between clinical groups. For analytical validation we tested correlations of results with existing methods that have been independently developed. These results provide a unified analysis model that can be utilized from GAAIN/LONI and CPAD to conduct harmonized analyses on multiple datasets. The full capabilities of this model will be explored in subsequent work.ConclusionThe proposed pipeline, which is going to be part of the publicly available GAAIN/LONI platform, should provide researchers with an optimized roadmap that describes how tau PET imaging data should be processed and analyzed for reliability and reproducibility in the context of drug development and regulatory decision making.

2023-12-01·Alzheimer's & Dementia

Harmonization of tau‐PET in Alzheimer’s disease: comparison of methods to derive CenTauR units for [18F]RO948, [18F]Flortaucipir, and [18F]MK‐6240

作者: Saad, Ziad S. ; Charil, Arnaud ; Kolb, Hartmuth C. ; Mathotaarachchi, Sulantha ; Jagust, William J. ; Rosa‐Neto, Pedro ; Collins, Jessica A. ; Rabinovici, Gil D. ; Tonietto, Matteo ; Iaccarino, Leonardo ; Johnson, Keith A. ; Baker, Suzanne L. ; Leuzy, Antoine ; Rowe, Christopher C ; Pascoal, Tharick A. ; Hostetler, Eric D. ; Klein, Gregory ; Bohorquez, Sandra Sanabria ; Dore, Vincent ; Lopresti, Brian J. ; Hutchison, R. Matthew ; Hansson, Oskar ; Villemagne, Victor L ; Mintun, Mark A. ; Raket, Lars Lau ; Pappas, Ioannis ; Carrillo, Maria C. ; Stephens, Andrew W. ; Karten, Yashmin ; Sivakumaran, Sudhir ; Haeberlein, Samantha Budd ; Pontecorvo, Michael J. ; Collins, Emily C. ; Higuchi, Makoto ; Ossenkoppele, Rik ; Irizarry, Michael C. ; Smith, Ruben

AbstractBackgroundTau positron emission tomography (PET) is increasingly used in the clinical evaluation of patients and as an outcome measure in Alzheimer’s disease (AD) clinical trials. Due to differences in tracer properties, instrumentation, and methods of analysis, however, tau‐PET outcome data cannot currently be meaningfully compared or combined. Here, we tested i) the feasibility of adapting the Centiloid method—an approach originally developed to standardize amyloid PET—to harmonize tau‐PET quantification (CenTauRs); ii) the performance of a non‐linear mixed model‐based approach (Joint Propagation Model) that does not require the use of a reference tracer.MethodHead‐to‐head tau‐PET data (Table 1) was included from two cohorts ([18F]RO948 vs [18F]flortaucipir, n = 37 [BioFINDER‐2]; [18F]flortaucipir [Avid A05] vs [18F]MK‐6240, n = 15, University of Pittsburgh) in which each participant was scanned with two tau‐PET tracers. Standardized uptake value ratio (SUVR) values were calculated using the inferior cerebellar cortex as the reference region. Anchor point data (Table 1) was derived for each tracer using the following criteria: CenTauR‐0, cognitively unimpaired (CU), amyloid PET negative (<10 Centiloids); CenTauR‐100, amyloid PET positive (>50 Centiloids), typical (temporoparietal) AD pattern on tau‐PET visual read, age<65 andMMSE>20. Regions‐of‐interest (ROIs) included a universal tau‐PET ROI—based on the intersection of tracer specific ([18F]flortaucipir, [18F]MK‐6240, [18F]PI‐2620, [18F]PM‐PBB3, [18F]GTP1 and [18F]RO948) masks that had been derived by subtracting average of amyloid‐negative CU images from the average AD image—as well as four subregions delineated within this ROI (medial temporal, meta‐temporal, temporoparietal and frontal) (Figure 1A). An overview of the adapted Centiloid‐like approach and the joint propagation model is shown in Figure 1B.ResultHigh R2 values were observed between tracers across all ROIs: [18F]RO948 vs [18F]flortaucipir, average 0.965 [range 0.923 (frontal) to 0.986 (universal)]; [18F]MK‐6240 vs [18F]flortaucipir, average 0.985 [range, 0.923 (medial temporal) to 0.991 (frontal)]. The Centiloid‐like and joint propagation model approaches provided near identical CenTauR values (Figure 2).ConclusionPreliminary findings support the development of standardized scale for tau‐PET using both a Centiloid‐like or joint propagation model approach. Additional data and consideration of the advantages and disadvantages of each will be needed to recommend one approach over the other.

2023-12-01·Alzheimer's & Dementia

Harmonization of tau‐PET in Alzheimer’s disease: comparison of methods to derive CenTauR units for [¹⁸F]RO948, [¹⁸F]Flortaucipir, and [¹⁸F]MK‐6240

作者: Collins, Jessica A. ; Haeberlein, Samantha Budd ; Charil, Arnaud ; Rosa‐Neto, Pedro ; Sivakumaran, Sudhir ; Higuchi, Makoto ; Collins, Emily C. ; Mathotaarachchi, Sulantha ; Pontecorvo, Michael J. ; Carrillo, Maria C. ; Lopresti, Brian J. ; Bohorquez, Sandra Sanabria ; Leuzy, Antoine ; Pascoal, Tharick A. ; Karten, Yashmin ; Pappas, Ioannis ; Saad, Ziad S. ; Baker, Suzanne L. ; Rowe, Christopher C ; Jagust, William J. ; Klein, Gregory ; Raket, Lars Lau ; Stephens, Andrew W. ; Kolb, Hartmuth C. ; Mintun, Mark A. ; Hansson, Oskar ; Smith, Ruben ; Hutchison, R. Matthew ; Villemagne, Victor L ; Dore, Vincent ; Iaccarino, Leonardo ; Tonietto, Matteo ; Johnson, Keith A. ; Hostetler, Eric D. ; Rabinovici, Gil D. ; Irizarry, Michael C. ; Ossenkoppele, Rik

AbstractBackgroundTau positron emission tomography (PET) is increasingly used in the clinical evaluation of patients and as an outcome measure in Alzheimer’s disease (AD) clinical trials. Due to differences in tracer properties, instrumentation, and methods of analysis, however, tau‐PET outcome data cannot currently be meaningfully compared or combined. Here, we tested i) the feasibility of adapting the Centiloid method—an approach originally developed to standardize amyloid PET—to harmonize tau‐PET quantification (CenTauRs); ii) the performance of a non‐linear mixed model‐based approach (Joint Propagation Model) that does not require the use of a reference tracer.MethodsHead‐to‐head tau‐PET data (Table 1) was included from two cohorts ([18F]RO948 vs [18F]flortaucipir, n = 37 [BioFINDER‐2]; [18F]flortaucipir [Avid A05] vs [18F]MK‐6240, n = 15, University of Pittsburgh) in which each participant was scanned with two tau‐PET tracers. Standardized uptake value ratio (SUVR) values were calculated using the inferior cerebellar cortex as the reference region. Anchor point data (Table 1) was derived for each tracer using the following criteria: CenTauR‐0, cognitively unimpaired (CU), amyloid PET negative (<10 Centiloids); CenTauR‐100, amyloid PET positive (>50 Centiloids), typical (temporoparietal) AD pattern on tau‐PET visual read, age<65 andMMSE>20. Regions‐of‐interest (ROIs) included a universal tau‐PET ROI—based on the intersection of tracer specific ([18F]flortaucipir, [18F]MK‐6240, [18F]PI‐2620, [18F]PM‐PBB3, [18F]GTP1 and [18F]RO948) masks that had been derived by subtracting average of amyloid‐negative CU images from the average AD image—as well as four subregions delineated within this ROI (medial temporal, meta‐temporal, temporoparietal and frontal) (Figure 1A). An overview of the adapted Centiloid‐like approach and the joint propagation model is shown in Figure 1B.ResultsHigh R2 values were observed between tracers across all ROIs: [18F]RO948 vs [18F]flortaucipir, average 0.965 [range 0.923 (frontal) to 0.986 (universal)]; [18F]MK‐6240 vs [18F]flortaucipir, average 0.985 [range, 0.923 (medial temporal) to 0.991 (frontal)]. The Centiloid‐like and joint propagation model approaches provided near identical CenTauR values (Figure 2).ConclusionsPreliminary findings support the development of standardized scale for tau‐PET using both a Centiloid‐like or joint propagation model approach. Additional data and consideration of the advantages and disadvantages of each will be needed to recommend one approach over the other.

项与 Cerveau Technologies, Inc. 相关的新闻（医药）

2024-07-23

·先通医药

先通医药海外参股公司Meilleur及其Aβ-PET显像剂NAV-4694被收购

近日,先通医药海外参股公司Meilleur及其用于治疗阿尔茨海默病的新一代Aβ-PET显像剂NAV-4694被纳斯达克上市公司Lantheus收购。美国国家老龄化研究所和阿尔茨海默病协会（NIA-AA）工作组最新发布的修订版指南指出，阿尔茨海默病应使用基于蛋白质的生物标志物进行生物学定义，包括Aβ和Tau在内的生物标志物可用于诊断阿尔茨海默病并提供其严重程度的指标。1 NAV-4694目前正处于临床Ⅲ期开发阶段，已被广泛用于学术和行业的研究性治疗试验。NAV-4694与Lantheus的下一代18F 标记Tau-PET显像剂MK-6240（florquinitau）形成互补，扩大了Lantheus的阿尔茨海默病诊断产品组合。 MK-6240是一款18F标记的高亲和力Tau蛋白PET显像剂。该药物对Tau蛋白的探测显像对比度高，可无创、精准、定位、定量地呈现阿尔兹海默病患者脑部Tau蛋白沉积的病理变化。此前，Lantheus通过收购Cerveau公司获得了MK-6240的全球权益，而先通医药是Cerveau的股东之一。根据现有的再许可协议，先通医药保留了MK-6240在中国的权益。 Aβ-PET阳性显像能够提示存在AD病理改变，结合Tau-PET检测结果，对AD早期诊断、鉴别诊断、抗Aβ治疗后疗效评价、AD药物临床试验患者筛选具有显著价值。根据协议条款，Lantheus 将支付预付款及潜在的额外开发和商业里程碑付款。此外，Lantheus 还将为研究收入和商业销售支付特许权使用费。该协议以股票购买的形式签订，规定Meilleur将在交易完成后的规定时间内提供过渡和临床开发服务。先通医药CEO唐艳旻表示：“这是一次激动人心的收购，我们非常看好Aβ-PET和Tau-PE在阿尔茨海默病早期诊断，临床分期及治疗前后疗效评估等方面的应用潜力,它们的联合使用将为阿尔茨海默病的诊疗决策提供有力的证据。” 在中国,先通医药则通过Aβ-PET显像剂欧韦宁®氟[18F]贝他苯注射液与Tau-PET显像剂MK-6240的组合,助力阿尔茨海默病患者实现早诊早治。参考文献 1.Jack CR, et.al. Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup. Alzheimer’s Dement 2024;1-27. https://doi.org/10.1002/alz.13859 先通医药是中国创新放射性药物领域的领先企业，专注于放射性药物的研发创新及落地应用以改善患者的健康水平。先通医药于2014年正式开展新一代放射性药物的研发，总部位于北京，在上海设有研发中心，在江苏、广东、四川建设有现代化放射性药物智能生产基地；同时，在美国设有分支机构，并与十几家跨国药企达成战略合作。全球放射性药物主要应用于神经、心血管、肿瘤三大疾病领域，先通医药已实现全面布局，并拥有20+精准诊断和靶向治疗放射性药物研发管线。凭借自身的研发优势，先通医药获得了投资机构的青睐，2020年4月至今，已成功募资超20亿元人民币，未来不久将登陆主要资本市场，成为中国放射性药物领域的创新力量。内容来源于网络，如有侵权，请联系删除。

并购放射疗法

2024-07-15

·FierceBiotech

Lantheus acquires Alzheimer’s PET diagnostic developer Meilleur Technologies

Lantheus pitched Meilleur’s amyloid-targeting NAV-4694 as a complement to its PET agent MK-6240, which is aimed at Alzheimer’s tau tangles. Lantheus is expanding its holdings of PET imaging agents for Alzheimer’s disease, with the acquisition of Meilleur Technologies. The deal grants Lantheus exclusive worldwide rights to Meilleur’s radiopharmaceutical diagnostic that highlights beta amyloid plaques in the brain. The injectable agent—known as NAV-4694, or F18-flutafuranol—is currently in phase 3 development. The acquisition comes just days after the Centers for Medicare and Medicaid Services proposed a separate payment pathway for certain diagnostic radiopharmaceuticals and nuclear medicine imaging agents—instead of bundling them as part of the procedure, as it had in the past. The change was put forward in CMS’ proposal for payment systems among hospital outpatient services and ambulatory surgical centers, set for the 2025 calendar year. Lantheus’ stock price jumped nearly 60% on the news. The deal also follows the FDA’s approval earlier this month of Eli Lilly’s Kisunla (donanemab-abzt) treatment for Alzheimer’s, seen as a challenger to Biogen and Eisai’s Leqembi in a newly burgeoning area of anti-amyloid therapies. “This acquisition solidifies our commitment to neurology, specifically for Alzheimer’s disease management, and reinforces our radiopharmaceutical leadership,” Lantheus CEO Brian Markison said in a statement, which pitched Meilleur’s NAV-4694 as a complement to the company’s PET agent MK-6240, aimed at Alzheimer’s tau tangles. The companies estimate that nearly 12 million people are living with mild cognitive impairment or Alzheimer’s disease in the U.S. today, a number that may pass 20 million by 2050. “With the combination of MK-6240 and NAV-4694, we are poised to provide important insights for guiding the use and assessing the impact of novel disease-modifying Alzheimer’s treatments,” Markison said. Lantheus previously acquired MK-6240, an F18-labeled agent also known as florquinitau, in February 2023 through its buyout of Cerveau Technologies. While the exact financial terms of Lantheus’ deal with Meilleur were not disclosed, the companies said the stock purchase agreement includes an upfront payment as well as additional R&D and commercial milestones, plus royalties. Meilleur will also provide transitional clinical development services for a set time. “We are excited by the potential of NAV-4694 for earlier identification of Alzheimer’s patients, empowering clinicians to select suitable candidates for timely therapeutic interventions,” said Meilleur CEO Rick Hiatt. “With Lantheus’ expertise in radiopharmaceutical diagnostics and ability to scale operations, I am confident that Lantheus is the ideal company to bring this late-stage biomarker through pivotal trials and into commercialization to one day benefit patients at risk of Alzheimer’s disease.”

并购临床3期诊断试剂

2024-05-27

·同写意

阿尔兹海默病走出“技术沉没周期”

本次大会以“创新工艺，成就医药产业未来”为主题，设1场主旨会议与3场平行分会，汇聚50余位来自抗体、ADC、GLP-1与多肽领域的专业讲者，聚焦下游工艺，进阶分离纯化新技术方法，共话医药产业未来！1906年，美国发明家德·福雷斯特发明了电子三极管，奠定了现代电子学的基石。然而，在人类突破电子学瓶颈后，却在医药领域遇到了新的“瓶颈”。在同年11月举行的第37届精神病学家会议上，一位名叫阿洛伊斯·阿尔茨海默的医生，向世界报告了一种全新的精神疾病。在对一例具有进行性痴呆表现的51岁女性遗体进行解剖后，他惊人的发现患者脑内遍布着大量深色淀粉样斑块。四年后，这种疾病被命名为阿尔茨海默病（简称AD）。此后100多年的时间中，无数学者、药企在阿尔茨海默病药物研发中投入大量的时间与金钱，然而换来的却只有一个又一个的失败案例。根据美国药物生产与研发协会发布的研究报告，仅2000-2017年间，全球累计在阿尔茨海默病药物上的研发投入就超过6000亿美元，失败的临床药物超过300种，失败率高达99.6%，占所有药物研发失败率首位。攻克阿尔茨海默病，不仅拥有极大的财富价值，甚至已经成为当今世界医药人迫切想要实现的梦想之一。1AD陷入“技术沉没周期”人们对于AD的探索，犹如盲人摸象，一直没有找到准确的方向。认知下降，是AD的典型特征，但它同时也是自然衰老的特征之一，两者之间的最大区别在于AD会加速认知下降的速度。即使如此，但这种认知下降也是一种极为漫长的过程，很可能长达二十年时间，如此长的时间跨度造成了人类攻克AD的道路举步维艰。图：衰老与阿尔兹海默病，来源：西部证券尽管人类已经与AD奋战百年，但却始终没有准确找到它的发病机制，一切仍旧是个谜团。为了接近真相，科学家提出了多种假说来进行验证，如Aβ级联假说、Tau蛋白异常磷酸化假说、胆碱能假说。但可惜的是，至今为止并没有哪一种假说得到了业界的公认，这才是为何人类在AD领域毫无收获的本质原因。01Aβ级联假说淀粉样斑块是AD的主要病理特征之一，它是由Aβ沉积形成，自然也就被认为是人类攻破AD的突破口之一。Aβ级联假说成为目前最主流的AD药物研发路径。这种假说认为，在正常生理条件下，Aβ的生成与清除处于一个动态平衡的过程，但在病理情况下，Aβ生成增多或者清除减少，导致平衡被打破。Aβ过度沉积在脑内从而引起了一系列的病理过程，这些病理过程反过来又使Aβ增多，形成了级联式的放大效应。图：Aβ级联假说示意图基于此，有科学家提出选择性结合和消除Aβ淀粉样蛋白聚集体的方式，以此来寻求扭转AD中的神经退行性过程。02Tau蛋白异常磷酸化假说AD患者的病理特征并非只有淀粉样斑块，神经元纤维缠结也是主要病理特征之一，它是由神经原纤维异常聚集而形成的，其主要成分是高度磷酸化的Tau蛋白。图：Tau蛋白过度磷酸化假说示意图，来源：中国银河证券当Tau蛋白发生高度磷酸化时，可以从微管中解离出来，失去对微管的稳定作用，导致物质运输受损、神经纤维退化，从而引起AD症状。03胆碱能假说胆碱能假说是最早的一种关于AD致病机理的学说。乙酰胆碱与人的认知和记忆密切相关，而AD患者脑内的胆碱能神经元出现严重缺失的情况，中枢胆碱能神经递质不足，从而导致定向力障碍、记忆减退、行为和个性改变等。目前已经上市的AD药物，大多数根据胆碱能假说研发的，但显然它们并没有完全解决人类在AD上的问题。致病因素成谜、病程进展周期长、临床指标差异大、诊断难度大，AD新药研发陷入长时间的“技术沉没周期”。2药企“研发黑洞”回溯药企AD研发历程，堪称一部人类药物研发失败史。2012年，强生/辉瑞的单抗药物Bapineuzumab的III期临床试验失败；2014年，罗氏宣告Gantenerumab的III期临床试验失败；2016年，礼来宣告III期临床药物Solanezumab没有达到主要临床终点；2017年，默沙东宣布停止开发BACE抑制剂药物Verubecestat；2018年，强生宣布其终止了BACE抑制剂剂Atabecestat II/III期临床试验……无数药企投入巨额资金却都折戟沉沙，不能不让人生出绝望的挫败感。在2021年之前，FDA仅批准过6种治疗AD的药物，包括：他克林（Tacrine）、多奈哌齐（Donepezil）、卡巴拉汀（Revastigmine）、加兰他敏（Galantamine）、美金刚（Menantine）以及美金刚/多奈哌齐复方制剂。图：获批上市的部分AD药物，来源：天风证券其中，前四种都是基于胆碱能假说而开发的乙酰胆碱酶（AchE）抑制剂；美金刚为N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，但这些药物都只能改善患者的症状，不能减轻AD的病理变化，也不能逆转或减缓疾病进程。同时，目前已获批的AchE抑制剂都有不同程度的副作用。1993年获批的他克林，会损伤线粒体，抑制DNA合成蛋白质，诱导细胞凋亡，导致严重的不良反应，临床表现主要是肝毒性和胃肠道反应，最终无奈退市；多奈哌齐是我国使用最多的AD药物，其严重不良反应表现包括神经紊乱（如躁狂症、攻击性行为和暴力行为等）。2019年，绿谷制药的甘露特钠胶囊在国内获批上市，用于治疗轻度至中度AD，改善患者的认知功能，是我国第一款治疗AD的原创新药。其作用机制是重塑肠道菌群，抑制肠道细菌氨基酸型神经炎症，从而抑制AD。然而，该药自上市以来就一直争议不断，主要疑问指向其Ⅲ期临床试验周期过短、效果评估依据不充分、药物作用机理阐释不明、疗效曲线突变诡异等方面。因此，即使进入医保后价格大幅下降，销售额也远没有想象中的理想。随着全球人口老龄化的加剧，AD患者数量持续升高，据World Alzheimer Report数据显示，2015年AD患者人数为4680万，预计2030年增长至7470万，到2050年时，这个数字将会达到1.3亿。“无药可治”的困境让AD成为全球暗藏机遇最大的药物品类，也有望成为继心血管疾病、脑血管疾病和癌症之后，全球第四大药物市场。3百炼终成钢传统疗法迟迟无法满足AD用药需求的情况下，人类终于在2021年取得了新的突破。2021年6月，FDA批准渤健的Aduhelm上市，这是第一款基于Aβ级联假说的药物，也是第一款治疗AD本身的药物。Aduhelm选择性识别Aβ构象表位的免疫球蛋白G1（IgG1）单克隆抗体，与患者脑组织中的Aβ沉积结合，激活免疫系统，清除大脑中的沉积蛋白，从而影响AD发病进程。基于临床数据，渤健向世人证明，Aduhelm可以显著使患者的淀粉样斑块减少，这也是它之所以能够获得FDA批准的原因。但这种淀粉斑块到底是不是阿尔兹海默症的诱发因素，依然存在争议，而Aduhelm并未向市场证明这一点，同时Aduhelm还存在明显的副作用，这也是它最终商业化失败的原因。不过，Aduhelm的失败并没有让渤健放弃AD药物研发，基于Aduhelm的失败经验，渤健在两年之后带着另一款产品Leqembi重新回到大众视野，让人们再次看到了攻克AD的曙光。2023年1月，FDA宣布完全批准由卫材和渤健联合开发的AD新药仑卡奈单抗（Leqembi），用于治疗早期AD患者的上市，成为全球首个能延缓AD进程的药物。2024年1月，该药在中国获批。III期临床研究结果表明，与安慰剂相比，Leqembi治疗组患者CDR-SB（量化痴呆症状的各种严重程度）下降减少了27%。在意向治疗（ITT）人群的分析中评分差异值为-0.451（p=0.00005）。在安全性方面，Leqembi显著降低了脑肿胀的发生率，接受Leqembi治疗的患者中仅有13%出现脑肿胀。由于其良好的安全性数据，上市后未被添加“黑框警告”。图：Leqembi达到了临床主要终点，来源：卫材公告Leqembi的成功获批初步验证了Aβ假说的有效性，是AD领域药物开发的标志性事件，被认为是AD治疗的新开端。在Leqembi上市的半年之后，礼来也实现了AD领域的突破，披露了AD新药Donanemab的最新完整3期临床数据。与安慰剂相比，接受Donanemab治疗的受试者进展到疾病下一阶段的风险降低了39%；52%的受试者在1年内达到了淀粉样蛋白斑块清除的要求，72% 的受试者在18个月内完成。从临床研究数据来看，Donanemab的疗效更优于Leqembi，礼来也就此提交了上市申请。不过，这并没有帮助Donanemab顺利上市，FDA在今年3月份最终决定推迟Donanemab药物的上市批准，并将组织外部专家会议讨论该药物的安全性和有效性。4AD研发终现曙光Leqembi的成功，打开了AD治疗领域新世界的大门，已然成为AD药物研发新路径。接下来，各大药企或将沿着这一路径开始进行疗效和安全性的比拼。除了Leqembi和Donanemab之外，在AD治疗领域，有127种潜在药物正在进行共164项临床试验。其中，处于III期临床阶段的试验共48项，涵盖32款药物；处于II期临床阶段的试验共90项，涵盖81款药物；处于I期临床阶段的试验共26项，涵盖25款药物。基于Aβ假说的疗法是其中资金和研究投入最多的类型，进入临床开发的产品还有礼来的Remternetug、Annovis Bio的buntanetap、勃林格殷格翰的iclepertin、阿斯利康/ Cerveau Technologies等。图：AD在研药物进展情况除靶向Aβ路径外，还有其他很多研发路线也在不断取得进展，包括在糖尿病和减肥领域大放异彩的GLP-1药物司美格鲁肽，针对AD适应症的开发正处于III期临床阶段。对于AD而言，越早发现，越早治疗，就越容易延缓病程。然而，目前尚没有针对AD的早筛产品上市。基于这一背景，不少药企选择跳过早期诊断环节，直接研发AD疫苗，希望通过自身免疫的方式清除Aβ淀粉样蛋白或Tau 蛋白，为治疗阿尔茨海默病开辟了另一条道路。这其中，AC Immune和强生共同研发的AD的疫苗ACI-24.060于2023年6月获得FDA授予的突破性疗法资格认定，目前正在进行II期临床试验。AD领域又燃起星星之火，有望点燃AD赛道长期被抑制的火焰，随着越来越多的资本入局，人类或将开始在AD赛道全力奔跑。更多优质内容，欢迎关注↓↓↓

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