The main purpose of this study is to investigate the safety and efficacy of the study drug solanezumab in participants with prodromal Alzheimer's disease (AD).

开始日期2016-06-01

申办/合作机构

Eli Lilly & Co.

NCT02614131

/ Terminated临床1期

Single-Dose and Multiple-Dose, Dose-Escalation Study With LY2599666 to Evaluate the Safety, Pharmacokinetics, and Tolerability in Healthy Subjects and Patients With Mild Cognitive Impairment Due to Alzheimer's Disease and Mild-to-Moderate Alzheimer's Disease

The main purpose of this study is to evaluate the safety and tolerability of the study drug known as LY2599666 in different groups of people - those who are healthy, those who have mild cognitive impairment due to Alzheimer's Disease (AD), and those with mild-to-moderate AD. The study will measure how much LY2599666 gets into the bloodstream and how long it takes the body to get rid of it. It will also evaluate how LY2599666 affects the body. The study has three parts. Part A will last about 2 months. Parts B and C will each last about 23 weeks. Participants may only enroll in one part.

开始日期2015-12-01

申办/合作机构

Eli Lilly & Co.

100 项与苏兰珠单抗相关的临床结果

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100 项与苏兰珠单抗相关的转化医学

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100 项与苏兰珠单抗相关的专利（医药）

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302

项与苏兰珠单抗相关的文献（医药）

2026-02-01·Neural Regeneration Research

Insights into the transcriptomic heterogeneity of brain endothelial cells in normal aging and Alzheimer’s disease

Article

作者: Hoi, Maggie Pui Man ; Lei, Chon Lok ; Yue, Qian ; Wan, Huaibin ; Zhang, Zaijun ; Li, Shang

Drug development for Alzheimer’s disease is extremely challenging, as demonstrated by the repeated failures of amyloid-β-targeted therapeutics and the controversies surrounding the amyloid-β cascade hypothesis. More recently, advances in the development of Lecanemab, an anti-amyloid-β monoclonal antibody, have shown positive results in reducing brain A burden and slowing cognitive decline in patients with early-stage Alzheimer’s disease in the Phase III clinical trial (Clarity Alzheimer’s disease). Despite these promising results, side effects such as amyloid-related imaging abnormalities (ARIA) may limit its usage. ARIA can manifest as ARIA-E (cerebral edema or effusions) and ARIA-H (microhemorrhages or superficial siderosis) and is thought to be caused by increased vascular permeability due to inflammatory responses, leading to leakages of blood products and protein-rich fluid into brain parenchyma. Endothelial dysfunction is an early pathological feature of Alzheimer’s disease, and the blood–brain barrier becomes increasingly leaky as the disease progresses. In addition, APOE4, the strongest genetic risk factor for Alzheimer’s disease, is associated with higher vascular amyloid burden, increased ARIA incidence, and accelerated blood–brain barrier disruptions. These interconnected vascular abnormalities highlight the importance of vascular contributions to the pathophysiology of Alzheimer’s disease. Here, we will closely examine recent research evaluating the heterogeneity of brain endothelial cells in the microvasculature of different brain regions and their relationships with Alzheimer’s disease progression.

2025-08-01·Japanese Journal of Radiology

Practical brain MRI guidelines for anti-Aβ antibody treatment in early symptomatic Alzheimer’s disease

Review

作者: Mori, Harushi ; Abe, Osamu ; Miki, Yukio ; Kakeda, Shingo ; Tokumaru, Aya M ; Kudo, Kohsuke ; Aoki, Shigeki

Abstract:

Purpose:

These guidelines aim to support magnetic resonance imaging (MRI) diagnosis in patients receiving anti-amyloid β (Aβ) antibody treatment without restricting treatment eligibility.

Materials and methods:

These guidelines were collaboratively established by Japan Radiological Society, The Japanese Society of Neuroradiology, and Japanese Society for Magnetic Resonance in Medicine by reviewing existing literature and the results of clinical trials.

Results:

Facility standards should comply with the “Optimal Use Promotion Guidelines” of Japan, and physicians should possess comprehensive knowledge of amyloid-related imaging abnormalities (ARIA) and expertise in brain MRI interpretation. The acquisition of knowledge regarding amyloid-related imaging abnormalities, brain MRI, anti-Aβ antibody introduction, and post-treatment diagnosis are also recommended.

Conclusion:

These guidelines facilitate the accurate diagnosis and effective management of ARIA; ensure the safe administration of anti-Aβ drugs; and provide a framework for MRI facilities, includes staffing requirements and the use of MRI management systems.

2025-06-24·NEUROLOGY

Changes in Daily Functioning in Association With Tau and Amyloid Among Unimpaired Older Adults With and Without Elevated Amyloid

Article

作者: Amariglio, Rebecca ; Rentz, Dorene M. ; Sperling, Reisa Anne ; Donohue, Michael C. ; Marshall, Gad A. ; Langford, Oliver ; Liu, Andy ; Dubbelman, Mark A. ; Aisen, Paul S. ; Raman, Rema

BACKGROUND AND OBJECTIVES:

Everyday functioning declines gradually over time in Alzheimer disease (AD), with the earliest changes potentially occurring at the preclinical stage. We investigated how changes in everyday functioning relate to (changes in) amyloid and tau in a large sample of cognitively unimpaired older adults, most of whom had elevated amyloid levels at the start of the study.

METHODS:

This prospective study included participants from a 240-week randomized controlled trial of an anti-amyloid drug, solanezumab, and individuals who screen-failed because of a negative amyloid PET scan. A subset (n = 434) underwent repeated tau PET scans. Participants and their study partners completed the Alzheimer's Disease Cooperative Study Activities of Daily Living Prevention Instrument multiple times during the double-blind phase of the trial. Using generalized least-squares models, fit by restricted maximum likelihood, we analyzed how changes in everyday functioning related to amyloid and tau PET. We also correlated changes in amyloid and tau PET with changes in everyday functioning.

RESULTS:

A total of 1,707 participants (71.5 ± 4.7 years, 60% female) showed a marginal decline in everyday functioning. Among individuals with elevated amyloid, those with the highest levels of neocortical and medial temporal tau showed the largest decline in everyday functioning, as reported by the participants and their study partners. Increases in neocortical and medial temporal tau correlated moderately (correlation coefficient ranging from -0.2 to -0.5) with a decline in ADCS ADL-PI scores. Functional changes were not evident with amyloid alone. At the item level, participants and their study partners were most likely to report increased difficulty at the last visit with completing complex activities and selecting and paying for items when shopping.

DISCUSSION:

Higher tau levels are associated with the fastest decline in everyday functioning in the presence of elevated amyloid, and those accumulating more tau show a faster decline in everyday functioning. These findings demonstrate the utility of including sensitive measures of everyday functioning in clinical practice and clinical trials at the stage of preclinical AD.

TRIAL REGISTRATION INFORMATION:

The A4 study, ClinicalTrials.gov ID: NCT02008357; and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration, ClinicalTrials.gov ID: NCT02488720.

172

项与苏兰珠单抗相关的新闻（医药）

2025-08-06

·汇聚南药

阿尔茨海默症重大突破！癫痫药涌现新机制

作者｜小麦 2025 年 7 月 27–31 日，第 18 届阿尔茨海默病协会国际会议（AAIC 2025）在加拿大多伦多召开，带来了阿尔兹海默症领域重大进展，如Lecanemab的四年长期数据首亮相， Donanemab的TRAILBLAZER-ALZ 2三期研究长期扩展（LTE）阶段结果显示早期用药获益更大，Trontinemab 快速深度清除斑块以及血液生物标志物指南首发等。癫痫病“新机制”药物研发呈现多点开花、快速推进的火热态势，包括KCNQ/Kv7 钾通道激动剂Azetukalner走向Ⅲ期， KCC2/NKCC1 氯离子转运体调节剂OV350从实验室到临床，5-HT2C受体超级激动剂Bexicaserin儿童发育性癫痫脑病（DEE）专研，神经活性类固醇Ganaxolone老靶点新剂型等等。 01 阿尔兹海默症发病机制阿尔茨海默病（AD）是一种起病隐匿的进行性发展的神经退行性疾病，对大脑造成损害，占所有痴呆症病例的60 - 70%，随着老年化的加剧，AD患者越来越多。 AD的发病具体机制至今仍未完全破译，目前的研究主要集中在以下几个方面： a. β-淀粉样蛋白（Aβ）级联假说；2. Tau蛋白异常磷酸化；3. 神经炎症等。Aβ传说是目前最经典的AD发病机制学说。淀粉样前体蛋白（APP）经过β-分泌酶（BACE1）和γ-分泌酶的异常切割，产生Aβ40和Aβ42两种主要的淀粉样蛋白。Aβ42更容易聚集形成寡聚体和淀粉样斑块，这些斑块沉积在大脑皮层和海马体等区域，干扰神经元的正常功能，导致神经毒性（图1）[1]。图1. Aβ蛋白的生成 AD巨大的市场吸引前仆后继，但是AD药物研发成本高、失败率也高，如诺华/安进的BACE1抑制剂umibecestat（CNP520）、罗氏的crenezumab、礼来的semagacestat、solanezumab以及lanabecestat、辉瑞与强生的bapineuzumab以及强生的atabecestat等都因没有达到临床终点而被终止。 2024年上半年，艾伯维的ABBV-916的中期分析结果显示，其疗效和安全性与已获批的Aβ单抗药物（如礼来的Donanemab和卫材/渤健的Lecanemab）相似，艾伯维因ABBV-916达不到差异化优势而终止其单药开发，AD的新药任重而道远。目前靶向Aβ治疗AD的单抗新药先后有Aducanumab、Lecanemab和Donanemab获批上市，然而Aducanumab上市后表现并不佳，它的临床试验结果存在争议，部分试验未能显示出明确的临床效益，由于疗效争议、高昂的价格以及医保覆盖有限，2024年1月渤健正式宣布决定停止所有用于治疗阿尔茨海默病的 aducanumab的开发和销售。 Lecanemab是由卫材与渤健联合研发的Aβ单抗，于2023年1月6日首次获 FDA 加速批准上市，随后于2023年7月6日获得完全批准，近期，卫材在2025年的阿尔茨海默病协会国际会议（AAIC）发布了Lecanemab的最新研究数据，包括： 1. 四年长期疗效数据：连续治疗4年后，69%的早期AD患者在CDR-SB评分上未恶化或有所改善，显示出疾病进展的显著延缓，相比自然病程，lecanemab治疗4年可延缓CDR-SB评分下降1.75分，相当于显著延长早期阶段持续时间。 b.皮下注射剂型（Subcutaneous, SC）进展：卫材已开发出自注射笔（autoinjector），皮下给药与静脉给药的疗效和生物标志物变化一致，有望成为长期居家治疗的新选择。 c.中期真实世界数据显示：84%接受lecanemab治疗的患者保持稳定或临床改善，安全性与III期研究一致。 2025年1月，美国FDA基于Clarity AD及其扩展研究的暴露-反应模型已批准lecanemab的“维持治疗”方案：在完成18个月每两周一次的初始治疗后，可转为每4周一次10 mg/kg静脉维持治疗[2]。 Donanemab是由礼来研发的一种靶向N端焦谷氨酸化Aβ的单克隆抗体，于2024年7月2日首次获得美国FDA批准上市，用于治疗出现早期症状的阿尔茨海默病成年人，近期的AAIC会议上，礼来公布了Donanemab的TRAILBLAZER-ALZ 2三期研究长期扩展（LTE）阶段的结果：接受Donanemab治疗的参与者在三年随访中持续表现出认知衰退减缓，且这一获益随时间推移不断扩大，与来自阿尔茨海默病神经影像学倡议（ADNI）的未治疗外部对照组相比差异显著[3]。研究还显示，即便推迟启动治疗，参与者仍可获益；但与推迟治疗者相比，更早开始使用Donanemab的参与者疾病进展至下一阶段的风险显著降低[3]。 AD的新药研发从未中断，目前在研的药物包括礼来的Remternetug、恒瑞医药的SHR-1707、罗氏的Trontinemab（RG6102）等（图2）。图2. 在研的阿尔兹海默症药物代表性药物 Remternetug Remternetug（LY3372993）是由礼来研发的新一代抗淀粉样蛋白（anti-amyloid）单克隆抗体，目前处于III期临床试验阶段，被视为阿尔茨海默病（AD）治疗从“对症治疗”迈向“早期干预甚至预防”的关键药物。早期的临床数据显示，经过 6 个月的治疗，41 名接受测试的人中有 75% 的大脑中的淀粉样蛋白被清除。而 Donanemab则用了18个月，清除了72% 的患者的淀粉样蛋白。 2020年7月，礼来开启Remternetug在AD患者中进行单独的1期研究。 30名临床诊断为AD或AD痴呆引起的轻度认知障碍的参与者在九个月内接受多次递增剂量的抗体或安慰剂。主要结果是严重不良事件的数量；次要结果包括药代动力学和脑淀粉样蛋白从基线到第25周的变化。2021年，礼来在该试验中增加了第二部分，额外招募了32名第一代日本血统的健康成年人接受单次抗体或安慰剂输注。在2021年和2022年，入组人数上调了两次，最终为224人，治疗期增加到61周，并且该研究增加了皮下给药。该试验在美国10个地点和3个日本地点进行，将持续到2024年11月。 2023年3月至4月在瑞典哥德堡举行的AD/PD会议上，礼来公布了Remternetug的中期1期研究结果：Remternetug能够快速且稳定地减少AD受试者的淀粉样斑块。在41名患有轻度认知障碍或轻度至中度阿尔茨海默病痴呆的受试者中，Remternetug显示出剂量依赖性的淀粉样蛋白降低效果，且安全性、耐受性良好[4]。目前，Remternetug正在开展多项临床试验，包括TRAILRUNNER-ALZ 2 Ⅲ期临床试验、TRAILRUNNER-ALZ 3Ⅲ期临床试验、Primary Prevention Trial预防性试验和国际多中心的Ⅲ期CTR20230785临床试验等。 2024 年 10 月，礼来启动了remternetug的一项在早期阿尔茨海默病患者中的TRAILRUNNER-ALZ 3 Ⅲ期试验，目的是测量与安慰剂相比，接受remternetug治疗的患者因阿尔茨海默病而出现或恶化记忆、思维或功能问题的时间差异。 TRAILRUNNER-ALZ 3 研究计划招募1,200名参与者进行为期18个月的皮下注射家庭治疗，然后进行盲法观察，以临床痴呆评分的主要终点为进展时间。次要结果包括CDR-SB以及一系列认知、行为和功能测试、血清抗体浓度和不良事件。参与者的血浆pTau217必须与淀粉样蛋白病理一致，并且没有或轻微的认知或功能障碍。该试验包括一项淀粉样蛋白和tau蛋白PET子研究，以及一项开放标签扩展，计划持续到 2030年（图3）[5]。图3. TRAILRUNNER-ALZ 3 研究计划 Remternetug具备“斑块清除更快、给药频率更低、干预时间更早”三大优势，有望在未来5年内成为首个获批用于“预防性治疗”阿尔茨海默病的药物。 SHR-1707 SHR-1707是由恒瑞医药开发的一种新型人源化抗Aβ IgG1单克隆抗体，能够特异性结合Aβ原纤维和单体，阻止Aβ斑块的形成，或促进小胶质细胞对Aβ的吞噬作用，用于治疗阿尔茨海默病（图4）。在体外药效学研究中，SHR-1707显示出比Lecanemab更强的效力。图4. 恒瑞神经类在研管线恒瑞分别在中国（CHN研究）和澳大利亚（AUS研究）分别开展了SHR-1707的两项随机、双盲、单次递增剂量的I期研究。 CHN研究包括两部分，在第一部分中，符合条件的健康年轻成年人（18-45岁）按8:2的比例依次随机分配到SHR-1707（五个剂量组：2、6、20、40和60 mg/kg）或安慰剂组；在第二部分中，老年受试者（55-80岁）按8:4的比例随机分配到SHR-1707（20 mg/kg）或安慰剂组。AUS研究采用了类似的设计，但仅纳入健康年轻成年人，并分为三个剂量组（2、20和60 mg/kg）（图5）。图5. SHR-1707的两项I期研究方案在CHN研究和AUS研究中，分别有62名（第1部分/第2部分，n = 50/12；年龄范围，18-42岁/55-63岁）和30名受试者（年龄范围，18-42岁）接受了SHR-1707或安慰剂治疗。在CHN研究中，所有与治疗相关的不良事件（TRAEs）均为轻度，在AUS研究中，TRAEs大多为轻度（SHR-1707组和安慰剂组各有1例中度事件）；SHR-1707组中最常见的TRAEs为味觉异常和疲劳（各占8.3%）。在两项研究中，SHR-1707的暴露量在2-60 mg/kg剂量范围内随剂量增加而略有超过剂量比例的上升；与安慰剂组相比，SHR-1707给药后血浆中Aβ42浓度呈剂量依赖性增加（图6）[6]。图6. SHR-1707的PK性质目前SHR-1707正在进行II期临床试验，旨在评估SHR-1707在轻度认知障碍（Mild Cognitive Impairment, MCI）或轻度阿尔茨海默病患者中的安全性、耐受性、药代动力学和药效学。该试验计划在中国的一个中心招募45名患者，分为5、10、20或40mg/kg的剂量组，每两周给药一次，持续六个月，随后进行为期一年的开放标签扩展。 Trontinemab Trontinemab 是由罗氏基于其专有的Brainshuttle技术，将β淀粉样蛋白结合单克隆抗体与转移受体（TfR1）穿梭模块相结合而得得一种双特异性2 +1淀粉样蛋白-β 抗体，专门设计用于增强进入大脑的通道，从而能够快速减少阿尔茨海默病患者的淀粉样蛋白。Trontinemab旨在有效运输穿过血脑屏障，以靶向聚集形式的β淀粉样蛋白并去除大脑中的淀粉样蛋白斑块（图7）。图7. Trontinemab结构与作用机制 2025年4月3日，罗氏在奥地利维也纳举行的AD/PD 2025阿尔茨海默病和帕金森病国际会议上公布了trontinemab的新数据。在1.8 或 3.6 mg/kg双盲期内，114名参与者对trontinemab的初步结果表明，通过淀粉样蛋白正电子发射断层扫描（PET）测量，大脑中的淀粉样蛋白斑块快速、深入、剂量依赖性减少。 28 周后，Trontinemab在3.6 mg/kg 剂量组中将 81% 的参与者（n=21/26）的淀粉样蛋白水平降低到24厘外阈值以下。阿尔茨海默病体液生物标志物的早期显著减少，包括脑脊液（CSF）和血浆中测量的总tau、磷酸化Tau（pTau）181、pTau217和神经颗粒蛋白（图8）[7]。图8. Trontinemab的临床疗效 2025年7月28日，罗氏在今年的AAIC会议上宣布Trontinemab正在进行的 Ib/IIa 期 Brainshuttle™ AD 研究的最新结果，再次验证 trontinemab 能够快速、显著地减少脑内淀粉样斑块以及针对早期有症状阿尔茨海默病的 III 期 FRONTIER 1 和 2 研究的设计方案，计划于年内启动。此外，罗氏今日还宣布，将在现有阿尔茨海默病开发项目中新增一项III 期试验，以评估 trontinemab在症状前阿尔茨海默病人群中的疗效。该试验将聚焦于认知衰退风险个体，旨在延迟或预防疾病进展至出现症状的临床阶段[8]。 02 癫痫病发病机制癫痫是一种以反复癫痫发作为表现的慢性脑部疾病。由脑部神经元异常放电引发，疾病的发作有反复性和短暂性特点。癫痫的发病机制复杂，涉及多种生物学过程和因素的相互作用，主要包括神经递质失衡、突触可塑性异常、离子通道功能障碍、炎症和免疫失调和氧化应激等（图9）[9]。图9. 癫痫病的发病机制目前的抗癫痫药物通过恢复兴奋性和抑制性神经递质的平衡来缓解症状，通过作用于产生动作电位的离子通道或调节突触传递的受体来减少神经元放电，但是，约30%的癫痫患者无法控制癫痫发作，急需新颖机制的抗癫痫药物，Ganaxolone是由Marinus Pharmaceuticals研发的一款GABA受体别构调节剂，于2022年3月被美国FDA批准上市，在两岁以上的患者中，用于治疗与细胞周期蛋白依赖性激酶样5（CDKL5）缺乏症（CDD）相关的癫痫发作，临床在研的新机制药物有Longboard Pharmaceuticals的Bexicaserin（LP352）、Neurocrine Biosciences的NBI-355和Cassava Sciences的Simufilam等（图10）。图10. 部分在研的抗癫痫药物代表性药物 Bexicaserin（LP352） Bexicaserin（LP352）是由Longboard Pharmaceuticals公司研发的一种新型5-HT2C受体超级激动剂，2024年10月，灵北公司（Lundbeck）宣布以约25亿美元收购Longboard Pharmaceuticals，获得了bexicaserin这一潜在“best-in-class”疗法，主要用于治疗与发育性癫痫性脑病（DEEs）相关的癫痫发作。 2024年1月，Longboard公布了PACIFIC研究的积极顶线数据，PACIFIC研究是一项Ⅰb/Ⅱa期双盲、安慰剂对照的临床试验，旨在评估Bexicaserin在DEEs患者中的安全性、耐受性、药代动力学和疗效。 PACIFIC研究结果显示在75天的治疗期内，Bexicaserin组的癫痫发作频率中位数降低了53.3%，而安慰剂组的癫痫发作频率中位数降低了20.8%。在特定DEEs亚型中，Dravet综合征患者癫痫发作中位数减少72.1%；Lennox-Gastaut综合征患者，癫痫发作中位数减少48.1%；其他DEEs患者：癫痫发作中位数减少61.2%，显示bexicaserin在减少癫痫发作频率方面具有显著效果（图11）[10]。图11. Bexicaserin的PACIFIC试验结果 2024年7月1日，Longboard宣布美国FDA已批准其研究药物Bexicaserin的突破性疗法认证，用于治疗两岁或以上患者与发育性和癫痫性脑病(DEEs)相关的癫痫发作，包括Dravet综合征。 2024年11月12日，Longboard宣布已启动Bexicaserin其全球3期DEEp OCEAN研究，评估其研究药物贝昔卡色林用于治疗2岁及以上参与者与发育性和癫痫性脑病（DEE）相关的癫痫发作。 2025年1月39日，灵北制药宣布了Bexicaserin为期 12 个月的 1b/2a 期 PACIFIC 试验的开放标签扩展的积极结果：在为期12个月的开放标签扩展研究中，Bexicaserin治疗组的可计数运动性癫痫发作频率中位数降低了59.3%。从安慰剂组转为Bexicaserin治疗的患者，12个月时癫痫发作频率中位数降低了58.2%[11]。 Azetukalner Azetukalner（XEN1101）是由 Xenon Pharmaceuticals 开发的一款高选择性、强效 Kv7.2/Kv7.3 钾通道开放剂，用于局灶性癫痫、原发性全面强直-阵挛癫痫发作以及重度抑郁症的治疗（图12）。图12. Azetukalner的临床进展 2025年4月，Jacqueline 等人在Epilepsia Open 杂志上报道了azetukalner 在局灶性癫痫成人患者中的一项 IIb 期临床试验（X-TOLE）后进行的长期开放标签扩展研究的中期疗效与安全性分析结果。 285 名受试者完成了双盲期（DBP），其中 275 人（96.5%）进入开放标签扩展期（OLE），全部进入 OLE 的 275 名受试者中56.4%（155/275）和 44.4%（122/275）分别实现 ≥50% 发作减少（≥6 个月与 ≥12 个月连续无发作）；28.4%（78/275）和 19.6%（54/275）分别实现 ≥90% 发作减少；22.2%（61/275）和 14.9%（41/275）分别实现完全无发作（100% 减少）的 ≥6 个月与 ≥12 个月连续期。在OLE中已治疗≥24个月的165名受试者中34.5%（57/165）和 23.6%（39/165）分别实现 ≥6 个月与 ≥12 个月的完全无发作。大多数不良反应为轻度或中度，主要包括头晕、头痛和嗜睡，表明azetukalner耐受良好，无新增安全信号[12]。 Azetukalner 正在进行两项X-TOLE2 与 X-TOLE3 实验，它们是两项完全相同的 III 期、多中心、随机、双盲、安慰剂对照试验，采用 1:1:1 随机、18 周双盲、固定剂量 25 mg/15 mg vs 安慰剂设计，主要终点为局灶性发作频率降低，旨在评估 azetukalner 作为附加治疗在年满 18 岁、已确诊局灶性癫痫、且正在服用 1–3 种抗癫痫药物（ASM）的成人患者中的临床疗效、安全性和耐受性，计划 2025 年底读出关键数据并支持 2026 年上市申请[13]。小结阿尔茨海默症和癫痫病的治疗药物研究不断进展，CNS药物开发难度大，失败率高，但是也都取得了进步，相继有获批和新颖机制的CNS药物，为患者提供了新的希望。未来的研究需进一步探索药物的机制、优化治疗方案，并关注药物对认知功能的影响。主要参考文献 1.Zixuan Zhao et.al, Current Anti-Amyloid-β Therapy for Alzheimer’s Disease Treatment: From Clinical Research to Nanomedicine, International Journal of Nanomedicine 2023:18 7825–7845 2.Latest data presented at AAIC 2025 reinforces lecanemab’s clinical effect with consistent safety profile 3.Lilly's Kisunla (donanemab-azbt) showed growing benefit over three years in early symptomatic Alzheimer's disease 4.Remternetug | ALZFORUM 5.A Study of Remternetug (LY3372993) in Early Alzheimer's Disease (TRAILRUNNER-ALZ 3) 6.Yaru Yang et.al, Safety, tolerability, pharmacokinetics and pharmacodynamics of a single intravenous dose of SHR-1707 in healthy adult subjects: two randomized, double-blind, single-ascending-dose, phase 1 studies, Alzheimer's Research & Therapy (2024) 16:218 7.Roche presents novel therapeutic and diagnostic advancements in Alzheimer’s at AD/PD 2025 8.Roche presents new insights in Alzheimer’s disease research across its diagnostics and pharmaceutical portfolios at AAIC 9.Tafere Mulaw Belete, Recent Progress in the Development of New Antiepileptic Drugs with Novel Targets, Annals of Neurosciences 30(4) 262 –276, 2023 10.Longboard Pharmaceuticals Initiates Phase 3 DEEp OCEAN Study Evaluating Bexicaserin in Developmental and Epileptic Encephalopathies (DEEs) 11.Lundbeck announces positive results from 12-month Open-Label Extension (OLE) of the PACIFIC trial evaluating bexicaserin in participants with Developmental and Epileptic Encephalopathies 12.Jacqueline A. French et.al, Interim analysis of the long- term efficacy and safety of azetukalner in an ongoing open- label extension study following a phase 2b clinical trial (X- TOLE) in adults with focal epilepsy, Epilepsia Open. 2025;10:539–548. 13.Xenon Pharmaceuticals: Azetukalner (FOS) 喜欢我们文章的朋友点个“在看”和“赞”吧，不然微信推送规则改变，有可能每天都会错过我们哦~ 免责声明 “汇聚南药”公众号所转载文章来源于其他公众号平台，主要目的在于分享行业相关知识，传递当前最新资讯。图片、文章版权均属于原作者所有，如有侵权，请在留言栏及时告知，我们会在24小时内删除相关信息。信息来源：BiG生物创新社往期推荐本平台不对转载文章的观点负责，文章所包含内容的准确性、可靠性或完整性提供任何明示暗示的保证。

临床结果AACR会议加速审批上市批准临床3期

2025-08-04

·EINPresswire

Biomed Industries Presents Four Breakthrough Studies on Alzheimer’s, Rett Syndrome, and Obesity Therapies at AAIC 2025

Biomed Industries, Inc. Presents Four Pivotal Studies at AAIC 2025 Highlighting Breakthrough Therapies for Alzheimer’s, Rett Syndrome, and Obesity NA-831 is the only drug to date that has halted Alzheimer’s disease progression. Combining it with existing drugs like Donanemab could optimize therapeutic efficacy and reduce serious side effects.” — Dr. Lloyd L. Tran, CEO of Biomed SAN JOSE, CA, UNITED STATES, August 4, 2025 / EINPresswire.com / -- Biomed Industries, Inc., a leading biopharmaceutical innovator developing transformative therapies for neurological and metabolic diseases, today announced the presentation of four major scientific papers at the Alzheimer’s Association International Conference (AAIC), held July 27–31, 2025, in Toronto, Canada. The presentations featured Biomed’s next-generation oral therapies for Alzheimer’s disease, Rett syndrome, and obesity, with a focus on novel combination strategies designed to enhance safety, efficacy, and accessibility. Featured AAIC 2025 Presentations: 1. The End of the Amyloid Era? Evidence for a Paradigm Shift in the Quest to Treat Alzheimer’s Disease 2. A Phase 3 Clinical Protocol of NA-831 Combined with Donanemab in Early Alzheimer’s Disease: A Placebo-Controlled, Double-Blind Study 3. Associations Between Alzheimer’s Disease and Rett Syndrome: Clinical Trials of NA-831 and NA-921 4. Neuro-Metabolic Link Between Alzheimer’s Disease and Obesity: Clinical Evaluation of NA-831 and NA-931 1. PRESENTATION: The End of the Amyloid Era? A Paradigm Shift in Alzheimer’s Research For over three decades, the “amyloid hypothesis” has dominated Alzheimer’s disease (AD) research, asserting that amyloid-β accumulation is a primary driver of neurodegeneration. Biomed’s comprehensive analysis of Phase 3 trial data from seven anti-amyloid drugs — including aducanumab, lecanemab, donanemab, gantenerumab, bapineuzumab, crenezumab, and solanezumab — challenges this paradigm. Across all trials, both treatment and placebo groups exhibited similar cognitive decline, as measured by CDR-SB and ADAS-Cog. The average differences between treatment and placebo arms were minor and not clinically significant (CDR-SB: -0.25; ADAS-Cog: -0.79). Slope comparisons further revealed near-identical rates of decline between groups. “Our analysis of Phase 3 clinical trial data for seven anti-amyloid drugs, including FDA-approved Aducanumab, Lecanemab, and Donanemab, indicates that none could halt disease progression in a clinically meaningful way — and all carried serious safety concerns,” said Dr. Zung Tran, VP of Biostatistics and AI at Biomed. 2. PRESENTATION: Phase 3 Clinical Protocol of NA-831 Combined with Donanemab NA-831, Biomed’s lead oral candidate, is a first-in-class therapy that promotes neuroprotection, neurogenesis, and memory enhancement. Phase 2 trials demonstrated its disease-modifying potential with a favorable safety profile compared to traditional anti-amyloid drugs. In this upcoming Phase 3 study, NA-831 will be evaluated in combination with Donanemab, a recently FDA-approved monoclonal antibody, to explore synergistic effects. The goal is to lower Donanemab dosing, thereby reducing risks such as cerebral edema and microbleeds, while enhancing cognitive outcomes. “NA-831 is the only drug to date that has halted disease progression in Phase 2 trials,” said Dr. Lloyd Tran, CEO of Biomed Industries. “Combining it with existing drugs like Donanemab could optimize therapeutic efficacy and reduce serious side effects.” 3. PRESENTATION: Alzheimer’s and Rett Syndrome: Shared Mechanisms and Dual Therapeutic Potential Biomed also presented findings on NA-921, a structural analog of NA-831 developed for Rett syndrome, a rare X-linked neurodevelopmental disorder. NA-921 modulates MeCP2 expression, targeting the disorder’s core epigenetic dysfunction. A double-blind, placebo-controlled Phase 2/3 trial (ClinicalTrials.gov ID: NCT06849973) demonstrated promising results: Clinical Global Impression–Improvement (CGI-I) at week 12: NA-921: 3.60 | Placebo: 3.83 | P = 0.0020 | Effect size = 0.42 NA-921 was well tolerated, with a significantly improved safety profile compared to trofinetide: - Diarrhea: Trofinetide 82%, NA-921 24%, Placebo 19% - Vomiting: Trofinetide 29%, NA-921 9%, Placebo 11% - Fever: Trofinetide 9%, NA-921 5%, Placebo 4% These findings underscore a possible biological link between Alzheimer’s disease and Rett syndrome, opening new cross-indication opportunities for NA-831 and NA-921. 4. PRESENTATION: Neuro-Metabolic Connections: NA-831 and NA-931 in Alzheimer’s and Obesity Biomed’s data also revealed compelling evidence of a neuro-metabolic bridge between Alzheimer’s disease, diabetes, and obesity. In addition to NA-831’s CNS benefits, Biomed is advancing NA-931, an oral quadruple receptor agonist (IGF-1, GLP-1, GIP, and glucagon) designed to treat obesity. In a 13-week Multiple Ascending Dose (MAD) study: - Mean body weight reduction: Up to 13.8% at 150 mg daily, 12.4% greater than placebo - ≥12% weight loss achieved by 72% of NA-931-treated patients vs. 2% in placebo group NA-931 demonstrated a strong safety profile, with mild and transient GI-related adverse events, and no observed muscle loss. “Our pipeline shows how targeting interconnected pathways across the CNS and metabolic systems can unlock significant clinical potential,” said Michael Willis, VP of Business Development. “With six active programs across Alzheimer’s, ALS, Rett syndrome, stroke, obesity, and MASH, we are building a diversified platform to accelerate innovation and value creation.” ABOUT BIOMED INDUSTRIES, INC. Biomed Industries, Inc. is a pioneering biopharmaceutical company committed to developing novel therapeutics that address unmet medical needs. Its innovative research platform has produced treatments for conditions including Alzheimer’s disease, ALS, Traumatic Brain Injury, Major Depressive Disorder, Diabetes, Obesity, MASH, Stroke, and rare diseases such as Huntington Disease and Rett Syndrome. (Website: https://www.biomedind.com ) Michael Willis Biomed Industries, Inc. email us here Visit us on social media: LinkedIn X Biomed introduction video Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

临床结果临床2期临床3期

2025-07-08

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JAMA子刊：受教育程度高竟成AD负面因素？队列研究发现，在存在显著淀粉样蛋白沉积的情况下，受教育程度高与tau蛋白积累更快有关

*仅供医学专业人士阅读参考在阿尔茨海默病（AD）的研究中，认知储备被认为是影响个体认知衰退进程的重要因素。其中，受教育程度（EA）作为认知储备的一个常用替代指标，近年来受到越来越多关注。已有研究表明，较高的教育水平通常与更佳的认知功能、更大的灰质体积、更高效的大脑网络功能以及更强的大脑内在连接性有关。不难得出结论，教育，似乎是面对AD的一个有利的因素。但今日发表在《JAMA·神经病学》上的一篇论文，却给出了反直觉的答案。来自深圳湾实验室神经疾病研究所的科研团队分析了3个独立队列、887名受试者样本，惊讶地发现，在β淀粉样蛋白（Aβ）阴性个体中，高教育程度与更缓慢的tau积累相关，表现出正面的作用；但在Aβ阳性人群中，高教育程度反而与更快的tau积累、更强的Aβ负荷、内嗅区tau水平以及血浆p-tau217浓度相关的tau积累有关，变成了一种负面因素。值得注意的是，Aβ靶向治疗可显著减轻Aβ阳性、高教育程度患者中p-tau217相关的tau积累，提示治疗可能在此类人群中具有更明显的益处。研究中采纳的三个队列研究分别是北美地区的阿尔茨海默病神经影像学计划（ADNI）、无症状阿尔茨海默病抗淀粉样蛋白治疗研究（A4），以及中国华南地区的大湾区健康老龄化脑研究（GHABS）。三个研究都有参与者的Aβ/tau蛋白PET数据。参与者按照受教育程度分为高低两组，在三个队列中选择的年限不同。在Aβ阴性组中，ADNI 17年、LEARN（即A4的阴性对照组） 16年、GHABS 14年；Aβ阳性组中，ADNI 16年、A4安慰剂组16年、A4 solanezumab治疗组16年、GHABS 11年。在Aβ阴性组中，教育水平高与多个脑区（包括颞叶、前额叶、顶叶和枕叶）tau蛋白积累更慢有关。但在Aβ阳性组中，教育水平高与特定区域tau积累加快相关，并观察到皮层tau蛋白扩散加快，提示tau蛋白可能更容易沿脑网络连接路径传播。这一加速扩散的模式主要集中在认知受损人群中，高教育水平个体还表现出更强的Aβ、内嗅皮质tau和血浆p-tau217相关的tau积累，以及未来更高的tau负荷风险。这些发现强调了在AD病理背景下，高认知储备个体可能存在更高的tau传播易感性。值得注意的是，研究者观察到，在A4队列中，虽然安慰剂组与治疗组在Aβ负荷、颞叶tau沉积或基线血浆p-tau217水平上无显著差异，但治疗组显示出血浆p-tau217升高速度和tau积累速度的显著下降。研究者认为，抗Aβ治疗可能对延缓特定人群的tau传播有一定益处。研究者指出，尽管高教育水平通常被视为认知保护因素，但在Aβ负荷存在时，可能因更强的脑连接性而加速tau传播。Aβ靶向治疗则可部分缓解该风险，特别是在高教育水平个体中。参考资料：[1]Cai Y, Fang L, Yang J, et al. Higher Educational Attainment and Accelerated Tau Accumulation in Alzheimer Disease. JAMA Neurol. Published online July 07, 2025. doi:10.1001/jamaneurol.2025.1801本文作者丨代丝雨

临床结果

100 项与苏兰珠单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10058	苏兰珠单抗	-	DB11756

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
遗忘	临床3期	美国	Eli Lilly & Co.	2014-02-28
遗忘	临床3期	日本	Eli Lilly & Co.	2014-02-28
遗忘	临床3期	澳大利亚	Eli Lilly & Co.	2014-02-28
遗忘	临床3期	加拿大	Eli Lilly & Co.	2014-02-28
认知障碍	临床3期	美国	Eli Lilly & Co.	2014-02-28
认知障碍	临床3期	日本	Eli Lilly & Co.	2014-02-28
认知障碍	临床3期	澳大利亚	Eli Lilly & Co.	2014-02-28
认知障碍	临床3期	加拿大	Eli Lilly & Co.	2014-02-28
阿尔茨海默症	临床3期	美国	Eli Lilly & Co.	2009-05-01
阿尔茨海默症	临床3期	日本	Eli Lilly & Co.	2009-05-01

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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


NCT04623242 (Pubmed)	临床2/3期	阿尔茨海默症	-	Solanezumab	艱艱觸鏇積衊窪簾製遞(簾觸淵淵鬱蓋鹹壓齋糧) = 憲積壓淵膚構窪獵鑰糧鹽鏇蓋鏇鹽簾醖餘醖築 (構鹽積齋獵顧範遞蓋鏇, 0.43)	-	2024-04-29
NCT02008357 (A4, Pubmed \| N Engl J Med)	临床3期	阿尔茨海默症	1,169	Solanezumab	選鑰膚憲鑰獵顧醖積遞(築積憲鏇艱壓壓製蓋鬱) = 願餘衊壓艱餘鏇壓膚淵憲製鹽遞蓋淵憲衊艱範 (鬱繭艱鹹網醖繭衊鹹淵 )	不佳	2023-09-21
				Placebo	選鑰膚憲鑰獵顧醖積遞(築積憲鏇艱壓壓製蓋鬱) = 願醖膚鬱糧鹽鹽窪蓋餘憲製鹽遞蓋淵憲衊艱範 (鬱繭艱鹹網醖繭衊鹹淵 )
NCT02760602 (ExpeditionPRO, CTgov)	临床3期	阿尔茨海默症	26	Solanezumab (Solanezumab)	襯獵製獵蓋醖鬱夢廠鏇(廠鹹範網顧壓憲製壓壓) = 衊製壓選艱蓋鬱鏇窪範襯鬱餘醖淵顧艱選鹽鹹 (範鹹遞齋襯鏇鑰夢窪艱, 壓餘製鹽夢鬱齋繭餘廠 ~ 築齋窪膚膚積窪夢簾廠) 更多	-	2018-07-24
				Placebo (Placebo)	襯獵製獵蓋醖鬱夢廠鏇(廠鹹範網顧壓憲製壓壓) = 鏇衊築願膚襯簾鏇襯構襯鬱餘醖淵顧艱選鹽鹹 (範鹹遞齋襯鏇鑰夢窪艱, 蓋簾鑰夢願鏇醖壓顧鹹 ~ 顧衊獵襯鹹鹹獵構鬱製) 更多
NCT01127633 (EXPEDITION EXT, CTgov)	临床3期	阿尔茨海默症	1,457	Placebo (Placebo)	衊繭廠齋鏇蓋鑰鏇簾鹽 = 築選艱顧觸築構鑰餘製夢觸鬱遞選願獵壓選簾 (選願糧鑰積衊膚範繭膚, 憲糧艱廠製積廠窪簾選 ~ 網餘繭遞範範獵淵淵築) 更多	-	2018-05-03
				Solanezumab (Solanezumab)	衊繭廠齋鏇蓋鑰鏇簾鹽 = 顧襯遞糧鑰夢遞遞壓範夢觸鬱遞選願獵壓選簾 (選願糧鑰積衊膚範繭膚, 鹽襯鬱獵壓簾觸廠膚醖 ~ 鑰鏇製築繭鹹淵鬱窪憲) 更多
NCT01900665 (EXPEDITION3 \| EXPEDITION 3, CTgov)	临床3期	阿尔茨海默症	2,129	Solanezumab (Solanezumab)	憲糧膚鏇壓鏇夢獵衊齋(選餘簾鏇築憲鹹憲簾鏇) = 選範夢選齋壓觸選觸鏇襯襯廠餘壓艱遞積築憲 (夢製簾鏇鹽繭製鏇積衊, 0.355) 更多	-	2018-03-14
				Placebo (Placebo)	憲糧膚鏇壓鏇夢獵衊齋(選餘簾鏇築憲鹹憲簾鏇) = 鏇製獵製遞窪鑰遞鹽構襯襯廠餘壓艱遞積築憲 (夢製簾鏇鹽繭製鏇積衊, 0.356) 更多
NCT01900665 (EXPEDITION3, Pubmed \| Br Dent J \| N Engl J Med) 人工标引	临床3期	阿尔茨海默症 \| 痴呆	2,129	Solanezumab	鬱鏇膚構顧艱構襯窪壓(鑰鹽築壓廠衊鏇築壓廠) = 蓋衊築鹹構淵窪選廠積艱艱窪願選鑰餘夢襯鏇 (窪願製築襯齋蓋廠選構 ) 更多	不佳	2018-01-25
				Placebo	鬱鏇膚構顧艱構襯窪壓(鑰鹽築壓廠衊鏇築壓廠) = 夢觸鹹鬱壓壓鹽築鬱選艱艱窪願選鑰餘夢襯鏇 (窪願製築襯齋蓋廠選構 ) 更多
NCT00904683 \| NCT01900665 \| NCT00905372 (EXPEDITION3, AAIC2017)	临床3期	阿尔茨海默症 amyloid pathology	-	Solanezumab	鏇鹽網艱餘獵鏇鏇獵範(鏇繭夢願齋膚衊獵願壓) = 獵製夢築壓廠選製獵蓋鹹願觸齋壓窪鏇顧獵膚 (衊壓衊憲窪蓋齋範鹹觸 ) 更多	-	2017-07-01