A Single Arm Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria With Inadequate Control of Intravascular Hemolysis on Currently Available C5 Inhibitor Therapy

This study is researching a treatment combination with two experimental drugs called pozelimab and cemdisiran referred to as "study drugs". Researchers are looking for a better way to treat Paroxysmal Nocturnal Hemoglobinuria (PNH).
The aim of the study is to see how well the pozelimab and cemdisiran combination works to lower hemolysis in participants whose PNH has been not well controlled even after taking other complement component 5 (C5) inhibitors, eculizumab/eculizumab biosimilar, ravulizumab or crovalimab.
The study is looking at several other research questions, including:
* What side effects may happen from taking the study drugs?
* How much of the study drugs are in the blood at different times?
* Whether the body makes antibodies against the study drug (which could make the study drugs not work as well or could lead to side effects)

开始日期2026-05-30

申办/合作机构

Regeneron Pharmaceuticals, Inc.

KCT0010985

/ Not yet recruiting临床3期

A SINGLE ARM STUDY TO EVALUATE THE EFFICACY AND SAFETY OF POZELIMAB AND CEMDISIRAN COMBINATION THERAPY IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA WITH INADEQUATE CONTROL OF INTRAVASCULAR HEMOLYSIS ON CURRENTLY AVAILABLE C5 INHIBITOR THERAPY

开始日期2025-12-01

申办/合作机构-

NCT06541704

/ Recruiting临床3期

A Multicenter, Randomized, Double-Masked, Placebo-Controlled Phase 3 Study of the Efficacy, Safety, and Tolerability of Subcutaneously Administered Pozelimab in Combination With Cemdisiran or Cemdisiran Alone in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration

This study is researching experimental (study) drugs called pozelimab and cemdisiran. The study is focused on participants who have Geographic Atrophy (GA) caused by Age-related Macular Degeneration (AMD). Geographic atrophy is a medical term that refers to later-stage cases of AMD which is an eye condition affecting central vision (what one sees straight ahead).
The purpose of this study is to evaluate the progression rate of Geographic Atrophy in eyes of patients treated with cemdisiran alone or in combination with pozelimab compared to those treated with placebo.
The study is looking at several other research questions, including:
* What side effects may happen from taking the study drug(s)
* How much study drug(s) are in the blood at different times
* Whether the body makes antibodies against the study drug(s) (which could make the study drug(s) less effective or could lead to side effects)

开始日期2024-10-30

申办/合作机构

Regeneron Pharmaceuticals, Inc.

100 项与 Cemdisiran 相关的临床结果

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100 项与 Cemdisiran 相关的转化医学

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100 项与 Cemdisiran 相关的专利（医药）

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项与 Cemdisiran 相关的文献（医药）

2026-04-01·LANCET

Efficacy and safety of cemdisiran siRNA in myasthenia gravis (NIMBLE): a double-blind, randomised, placebo-controlled, phase 3 trial

Article

BACKGROUND:

Autoantibody-mediated complement activation drives pathology in acetylcholine receptor (AChR) antibody-positive generalised myasthenia gravis. Newer targeted therapies lower overall antibody concentrations or inhibit complement activity. We aimed to evaluate an siRNA (cemdisiran) targeting complement component 5 (C5) as monotherapy and in combination with a C5 antibody (pozelimab) in generalised myasthenia gravis.

METHODS:

NIMBLE is a randomised, double-blind, placebo-controlled, phase 3 trial conducted at 86 centres in 13 countries. We enrolled patients aged 18 years or older with a diagnosis of generalised myasthenia gravis, positive serology for anti-AChR or anti-LRP4 antibodies, and a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or greater. Patients were randomly allocated to receive cemdisiran monotherapy (600 mg every 12 weeks; cemdisiran group), pozelimab monotherapy (200 mg every 4 weeks; pozelimab group), combined cemdisiran (200 mg every 4 weeks) and pozelimab (200 mg every 4 weeks; combination group), or placebo, all administered subcutaneously, during a 24-week double-blind treatment period. The primary endpoint was change from baseline in MG-ADL scores at week 24, assessed in the modified intention-to-treat (mITT) primary analysis set (the first 245 randomly allocated patients who received any dose of study treatment and had at least one post-baseline assessment). A prespecified hierarchal statistical testing strategy was used; multiplicity was controlled for comparisons of cemdisiran versus placebo and combination versus placebo (pozelimab was not statistically tested against placebo and was used only to assess the contribution of components to the combination treatment). Safety was mainly assessed by recording of treatment-emergent adverse events in all patients who received any dose of study treatment. This study is registered with ClinicalTrials.gov (NCT05070858); the current status is active, not recruiting.

FINDINGS:

Between Jan 20, 2022 and July 18, 2025, 390 participants were screened and, as of the data cut-off presented in this report (July 8, 2025), 284 were randomly allocated to the cemdisiran group (79 [28%] patients), pozelimab group (50 [18%]), combination group (80 [28%]), and placebo group (75 [26%]). Of 277 patients who received any study treatment, 263 (95%) completed the double-blind treatment period. In the mITT primary analysis set, at week 24, the least-squares mean change from baseline in MG-ADL total score was -4·5 (SE 0·4) in the cemdisiran group (n=64), -4·0 (0·4) in the combination group (n=67), and -2·2 (0·5) in the placebo group (n=59). Placebo-adjusted least-squares mean differences in MG-ADL score at week 24 were -2·3 (SE 0·7; 95% CI -3·6 to -1·0; p=0·0005) in the cemdisiran group and -1·7 (0·7; -3·0 to -0·4; p=0·0086) in the combination group. The proportion of participants with at least one adverse event during the double-blind treatment period was 54 (69%) of 78 in the cemdisiran group, 65 (81%) of 80 in the combination group, 40 (82%) of 49 in the pozelimab group, and 54 (77%) of 70 in the placebo group. The most common adverse event in the cemdisiran group was upper respiratory tract infection (nine [12%] of 78 patients), which occurred at a similar incidence in the placebo group (eight [11%] of 70). No serious or meningococcal infections occurred in the cemdisiran group. Adverse events leading to treatment discontinuation occurred in two participants (3%) in the placebo group and one participant (2%) in the pozelimab group. No deaths occurred during the double-blind treatment period. Two deaths occurred after the double-blind treatment period, one of which was assessed as treatment-related by the investigator but not treatment-related by the sponsor.

INTERPRETATION:

Cemdisiran monotherapy and combination therapy were effective in the treatment of generalised myasthenia gravis, and were generally well tolerated. Subcutaneous dosing of cemdisiran, administered every 3 months, could provide a convenient treatment approach for generalised myasthenia gravis.

FUNDING:

Regeneron Pharmaceuticals.

2025-12-22·Cureus Journal of Medical Science

Emerging Therapies in IgA Nephropathy: From A Proliferation-Inducing Ligand (APRIL) and B-cell Activating Factor (BAFF) Inhibitors to Precision Medicine

Review

作者: Panta, Raju ; Sharma, Ishwor

IgA nephropathy (IgAN) is the most prevalent primary glomerular disease worldwide and a significant contributor to end-stage kidney disease (ESKD). Traditional management has centered on supportive care and non-specific immunosuppression, but recent advances in the understanding of pathogenic pathways have catalyzed the development of targeted therapies. This review synthesizes current evidence on evolving treatments, with a focus on A Proliferation-Inducing Ligand (APRIL) and B-cell Activating Factor (BAFF) (e.g., sibeprenlimab, atacicept, povetacicept, telitacicept), complement pathway modulators (e.g., iptacopan, cemdisiran, ravulizumab), and novel agents such as felzartamab and sparsentan. It also explores precision medicine strategies, including biomarker-guided therapy, individualized risk stratification, and combination regimens. Supported by high-quality recent clinical trial data and the latest kidney disease outcome guidelines, these innovations represent a paradigm shift toward personalized, disease-modifying treatment in IgAN, offering a new horizon for improved renal outcomes and long-term disease control.

2025-08-01·EJHaem

Safety, Efficacy, and Patient‐Reported Outcomes From a Phase 2 Randomized Trial of Pozelimab and Cemdisiran Combination in Patients With Paroxysmal Nocturnal Hemoglobinuria

Article

作者: Pavani, Rodrigo ; Wong, Raymond Siu Ming ; Perlee, Lorah ; Mohan, Kosalai ; Souttou, Amal ; Kelly, Richard J. ; Meagher, Karoline ; Hartford, Christopher ; Sherman, Steven ; Aurand, Lisa ; Rofail, Diana ; Jang, Jun‐Ho ; Nguyen, Quang

ABSTRACT:

Introduction:

Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra‐rare, life‐threatening disease associated with chronic intravascular hemolysis due to uncontrolled complement activation. PNH results in anemia with an increased risk of thrombosis, and often causes severe fatigue, and decreased physical function and health‐related quality of life (QoL). We investigated the efficacy, safety, and patient‐reported outcomes data of the combination of pozelimab (a fully human monoclonal antibody) and cemdisiran (an N‐acetylgalactosamine‐conjugated small interfering ribonucleic acid) from a Phase 2 trial (NCT04811716) in patients with PNH who transitioned from pozelimab monotherapy.

Methods:

In this randomized, open‐label, Phase 2 study, patients were randomized (1:1) to one of two treatment arms; both arms received subcutaneous cemdisiran 200 mg every 4 weeks (Q4W) plus subcutaneous pozelimab 400 mg either Q4W (Arm 1) or every 2 weeks (Arm 2).

Results:

Twenty‐four patients were treated with combination dosing. During the 28‐week open‐label treatment period (OLTP), 20 patients (83.3%) maintained control of lactate dehydrogenase (≤ 1.5 × upper limit of normal) at all timepoints. The majority of patients (92%) did not require a blood transfusion. While most patients (66.7%) experienced treatment‐emergent adverse events, the majority of these events were mild to moderate in severity. No meningococcal infections, thrombotic events, or deaths were reported. The combination therapy maintained improvements in patient‐reported fatigue, physical functioning, and QoL throughout the OLTP.

Conclusion:

Combination treatment maintained adequate hemolysis control and was generally well tolerated. Administration of pozelimab Q2W did not improve disease control as compared to pozelimab Q4W.

Trial Registration:

ClinicalTrials.gov/NCT04811716

192

项与 Cemdisiran 相关的新闻（医药）

2026-06-05

·细胞基因治疗前沿

20亿美元！小核酸龙头押注AI，重塑RNAi药物发现

注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。 2026年6月3日，RNAi治疗领域开创者Alnylam Pharmaceuticals（NASDAQ: ALNY）宣布与硅谷AI初创公司Inceptive Nucleics达成战略合作，交易总价值高达20亿美元。根据协议，Alnylam将支付3000万美元预付款（含现金和Inceptive股权购买），Inceptive另有资格获得基于临床前、监管和商业销售里程碑的额外付款。受此消息提振，Alnylam股价当日收涨2.26%。图片来源：Alnylam公司官网 Transformer架构发明人的跨界一击 Inceptive成立于2021年，总部位于硅谷帕洛阿尔托，在柏林和苏黎世设有办事处。公司的灵魂人物是联合创始人兼CEO Jakob Uszkoreit——他是2017年里程碑论文《Attention is All You Need》的核心作者之一，即「Transformer八子」中的一员。Uszkoreit不仅是Transformer架构的主要贡献者，还是「Transformer」这个名字的提出者。正是这一架构奠定了ChatGPT等大语言模型的基础。Uszkoreit在Google Brain工作13年后于2021年离职创办Inceptive，将Transformer的底层逻辑迁移至RNA「生物语言」建模。联合创始人Rhiju Das是斯坦福大学医学院生物化学副教授，曾在大卫·贝克实验室从事博士后研究，专注于RNA分子的计算机建模和设计。 Inceptive的核心技术是「生命基础模型」（Foundation Models of Life）。与传统AI制药公司针对单一任务训练专用模型不同，Inceptive的模型具有跨模态泛化能力——可在siRNA、反义寡核苷酸、多肽、mRNA等多种序列类药物之间直接迁移使用，无需为每种分子类型重新训练。这种通用性源于模型对生物学底层规律的学习，而非对特定任务的拟合。在双方的前期探索性合作中，Inceptive模型在数周内即展现出卓越性能，能从相对较小的数据集中提取有意义的生物学洞见来表征siRNA分子。Inceptive还在布局体内CAR-T方向，凭借极少的CAR-T特异性训练数据，设计出符合行业领先基准的mRNA序列。 Inceptive已获得两轮融资：2021年2000万美元种子轮和2023年1亿美元A轮，后者由a16z Bio+Health和英伟达风险投资部门NVentures领投，S32和Obvious Ventures跟投。小核酸药物的绝对王者 Alnylam是RNAi治疗领域的开创者和领导者，2002年创立于马萨诸塞州剑桥市，基于诺贝尔奖获奖的RNAi科学，已成功开发出六款获批药物，覆盖70多个国家。这六款药物分别是：其中Amvuttra凭借皮下注射、每季度给药一次的便利性，以及2025年ATTR心肌病适应症的扩展，已成为全球小核酸药物销售冠军。 2026年第一季度，Alnylam实现营收11.7亿美元；每股收益1.99美元。产品净收入达10.36亿美元，同比增长121%，这是公司首次单季产品收入突破10亿美元。管线方面，Alnylam正在推进多个重磅潜力项目。 Zilebesiran是一款靶向血管紧张素原的siRNA降压药，2023年7月罗氏以28亿美元总交易额获得合作权益，目前ZENITH全球III期心血管结局试验已启动，计划入组约11000名患者，CDE已于2026年6月拟纳入突破性疗法。Cemdisiran正在III期开发中，用于阵发性睡眠性血红蛋白尿症和地图样萎缩。Elebsiran靶向丁型肝炎病毒正处于临床阶段。此外还有Mivelsiran、ALN-6400和ALN-HTT02等早期项目。Alnylam 2030战略的目标正是将这些管线潜力加速兑现，而与Inceptive的合作正是该战略的重要落子。图片来源：Alnylam公司官网关于AI加注RNAi RNAi药物设计面临的搜索空间几乎是天文数字级别：siRNA序列选择、化学修饰策略、递送方案的组合优化，远非人力穷举所能覆盖。Inceptive的AI模型试图从根本上改变这一范式：先预测，后验证。此次合作中，双方将共同建模靶标mRNA，探索序列空间和新颖化学修饰以增强药效，并预测在临床前模型中表现最优的治疗候选物，帮助Alnylam优先推进最有前景的分子，提升实验效率。 Uszkoreit对此评价道：「大多数药物设计仍在试错，测试成千上万个分子然后期望有东西管用。Inceptive建立在一个不同的前提上：生命遵循的规则如此复杂，只有AI才能学习它们。」 Alnylam CEO Yvonne Greenstreet则表示：「我们将以此前不可能的速度、创意和精度，加速创造变革性药物。」值得关注的是，AI制药正在成为2026年生物医药领域最活跃的交叉前沿。仅今年上半年，百时美施贵宝牵手Anthropic、Isomorphic Labs融资21亿美元、Incyte接连与Genesis和Edison Scientific达成合作，Alnylam与Inceptive的联手是这股浪潮中金额最大的RNAi专项合作。总结 20亿美元的AI合作能否为Alnylam打开估值修复的窗口，取决于一个更本质的问题：AI预测的siRNA候选物能否真正转化为更高的临床成功率？这个答案需要时间，但Alnylam已经用20年和六款获批药物证明——在RNAi领域，它有足够的耐心和能力将科学愿景变为商业现实。参考资料：公司官网扫码进群掌握CAR-T疗法、干细胞疗法、基因疗法、溶瘤病毒、核酸药物全方位信息

2026-05-27

·中国生物器材网

C3 siRNA补体系统介绍及相关药物研发新进展

2026年5月，圣因生物宣布其靶向补体C3的siRNA药物SGB-9768获NMPA临床试验批准，适应症拓展至补体介导的血液疾病，包括阵发性睡眠性血红蛋白尿症（PNH）和非典型溶血尿毒综合征（aHUS）。这标志着SGB-9768在补体疾病治疗领域的进一步突破——此前该药已获得补体介导的肾脏疾病（IgA肾病、C3肾小球病、免疫复合物介导的膜增生性肾小球肾炎）的临床试验批准，目前正开展Ⅱ期临床研究。作为国内首款靶向补体C3的siRNA在研药物，SGB-9768采用创新的GalNAc肝脏递送技术，通过RNAi机制精准抑制C3表达。Ⅰ期临床数据显示，单次皮下给药即可实现剂量依赖性、显著且持久的C3水平降低与补体通路活性抑制，同时展现出良好的安全性和耐受性，具备同类最优潜力。一、补体系统补体系统（complement system）是广泛存在于血清、组织液和细胞膜表面的一组蛋白质，包括30多种蛋白质，是一个具有精密调控机制的蛋白质反应系统。补体系统由三类成分构成：补体固有成分：包括经典激活途径的C1、C2、C4；旁路途径的B因子、D因子和P因子（备解素）；凝集素途径的甘露糖结合凝集素（MBL）；以及三条激活途径共同的C3、C5、C6、C7、C8和C9。补体调节蛋白：包括C1抑制物、I因子、H因子、衰变加速因子（DAF）、膜辅因子蛋白（MCP）等。补体受体：包括补体受体1~5（CR1~CR5）和过敏毒素受体（C3aR和C5aR）等。补体蛋白通常是共同发挥作用消灭病原体，并能向其他免疫系统成员发出开始进攻的信号。补体只有被激活后才具有生理活性，补体激活有三条途径，根据起始分子的不同，分为经典途径（免疫复合物启动）、凝集素途径（糖组分启动）和旁路途径。主要有以下三条激活途径：经典途径（Classical pathway，CP）：由抗原-抗体复合物激活，C1识别抗体结合抗原后启动级联反应。替代途径（Alternative Pathway，AP）：与经典途径依赖抗体激活的特性不同，旁路途径无需抗体参与即可激活，由C3、B、D、P因子直接参与，通常在病原体感染的早期阶段发挥先天免疫作用，快速抵御病原体入侵。凝集素途径（Lectin Pathway，LP）：补体系统的第三条激活途径，由病原微生物表面的糖结构甘露糖结合凝集素（MBL）启动。图1. 补体级联反应[1] 无论从哪条途径启动，补体系统最终都会在C3汇合并向下级联通过C5，C5可被C5转化酶裂解为小片段C5a和大片段C5b，C5a游离于液相，诱发炎症反应的强效促炎因子，能够与其受体C5aR或C5L2结合发挥过敏毒素、趋化因子等活性；C5b可与C6结合为稳定的C5b6复合物，继而自发与C7、C8、C9结合为C5b-9复合物，被称为攻膜复合物（membrane attack complex，MAC），该复合物可直接刺破细胞，导致细胞渗透压失衡而溶解死亡。二、补体系统相关药物研发进展作为机体免疫系统的重要组成部分，补体系统参与调节炎症反应、免疫应答和组织修复等生理过程。然而，补体失效或过度激活也会导致多种疾病，如缺血性中风、脓毒症等急性炎症，牙周病、眼部疾病等慢性炎症，红斑狼疮等自身免疫性疾病；此外，一些肿瘤、肾病、神经退行性疾病、慢性溶血、血栓性微血管病等也与补体系统异常有关。图2. 补体在人类疾病中的作用机制[2] 由于补体系统蛋白丰度高、作用机制复杂，早期补体抑制剂的开发多以单抗为主，且大多集中在终末途径的C5靶点（如依库珠单抗）。但当下的研发趋势正发生深刻变革：一方面，靶点上移成为追求，C3作为三条通路的交汇点，靶向C3可实现更上游的广谱阻断；另一方面，剂型革新正提升患者依从性，siRNA疗法正在崛起，例如圣因生物开发的靶向C3的siRNA药物SGB-9768，通过皮下注射即可实现持久、深度基因沉默，已获NMPA批准开展PNH和aHUS临床试验。表1. 部分补体靶向药上市药物三、补体系统人源化小鼠在药物靶点人源化模型研究领域（如南模生物），针对补体系统靶点开发了一系列人源化小鼠模型，模型信息详见下表，欢迎咨询。表2. 补体系统靶点人源化小鼠 hC3，目录号：NM-HU-233778 图3. hC3小鼠血清中mC3和hC3的蛋白表达（A），体重及生存曲线（B），肝脏及肾脏H&E染色（C）和血生化指标检测（D）。 ARO-C3在hC3小鼠体内的药效评估图4. ARO-C3在hC3小鼠体内的药效评估。结果表明，单次注射ARO-C3后，hC3小鼠血清中人补体C3（hC3）水平降低，存活率得到改善。 hC5(Plus)，目录号：NM-HU-241686 图5. ELISA法检测血清中人C5（A）和小鼠C5（B）的表达水平。 Cemdisiran(ALN-CC5)在hC5与hC5(Plus)小鼠中药效评价 Cemdisiran（ALN-CC5）是一种小干扰RNA（siRNA）药物，主要用于治疗由补体系统异常引起的疾病。其作用机制是通过靶向肝脏中的C5基因，抑制C5蛋白的合成，从而减少补体系统的激活，减轻炎症反应。图6. 使用ELISA检测Cemdisiran（ALN-CC5）治疗后hC5及hC5(Plus)小鼠血清中人C5表达水平。结果表明，Cemdisiran（ALN-CC5）可有效清除hC5和hC5(Plus)小鼠体内的人C5蛋白。 Reference： [1] Batista AF, Khan KA, Papavergi MT, Lemere CA. The Importance of Complement-Mediated Immune Signaling in Alzheimer's Disease Pathogenesis. Int J Mol Sci. 2024;25(2):817. Published 2024 Jan 9. doi:10.3390/ijms25020817 [2] Meuleman MS, Duval A, Fremeaux-Bacchi V, Roumenina LT, Chauvet S. Ex Vivo Test for Measuring Complement Attack on Endothelial Cells: From Research to Bedside. Front Immunol. 2022;13:860689. Published 2022 Apr 12. doi:10.3389/fimmu.2022.860689 关于我们上海南方模式生物科技股份有限公司（Shanghai Model Organisms Center, Inc.，简称"南模生物"），成立于2000年9月，是一家上交所科创板上市高科技生物公司（股票代码：688265），始终以编辑基因、解码生命为己任，专注于模式生物领域，打造了以基因修饰动物模型研发为核心，涵盖多物种模型构建、饲养繁育、表型分析、药物临床前评价等多个技术平台，致力于为全球高校、科研院所、制药企业等客户提供全方位、一体化的基因修饰动物模型产品解决方案。

2026-05-27

·南模生物SMOC

C3 siRNA再拓适应症！从药物到模型，补体赛道火热升级进行时

2026年5月，圣因生物宣布其靶向补体C3的siRNA药物SGB-9768获NMPA临床试验批准，适应症拓展至补体介导的血液疾病，包括阵发性睡眠性血红蛋白尿症（PNH）和非典型溶血尿毒综合征（aHUS）。这标志着SGB-9768在补体疾病治疗领域的进一步突破——此前该药已获得补体介导的肾脏疾病（IgA肾病、C3肾小球病、免疫复合物介导的膜增生性肾小球肾炎）的临床试验批准，目前正开展Ⅱ期临床研究。作为国内首款靶向补体C3的siRNA在研药物，SGB-9768采用创新的GalNAc肝脏递送技术，通过RNAi机制精准抑制C3表达。Ⅰ期临床数据显示，单次皮下给药即可实现剂量依赖性、显著且持久的C3水平降低与补体通路活性抑制，同时展现出良好的安全性和耐受性，具备同类最优潜力。补体系统补体系统（complement system）是广泛存在于血清、组织液和细胞膜表面的一组蛋白质，包括30多种蛋白质，是一个具有精密调控机制的蛋白质反应系统。补体系统由三类成分构成：补体固有成分：包括经典激活途径的C1、C2、C4；旁路途径的B因子、D因子和P因子（备解素）；凝集素途径的甘露糖结合凝集素（MBL）；以及三条激活途径共同的C3、C5、C6、C7、C8和C9。补体调节蛋白：包括C1抑制物、I因子、H因子、衰变加速因子（DAF）、膜辅因子蛋白（MCP）等。补体受体：包括补体受体1~5（CR1~CR5）和过敏毒素受体（C3aR和C5aR）等。补体蛋白通常是共同发挥作用消灭病原体，并能向其他免疫系统成员发出开始进攻的信号。补体只有被激活后才具有生理活性，补体激活有三条途径，根据起始分子的不同，分为经典途径（免疫复合物启动）、凝集素途径（糖组分启动）和旁路途径。主要有以下三条激活途径：经典途径（Classical pathway，CP）：由抗原-抗体复合物激活，C1识别抗体结合抗原后启动级联反应。替代途径（Alternative Pathway，AP）：与经典途径依赖抗体激活的特性不同，旁路途径无需抗体参与即可激活，由C3、B、D、P因子直接参与，通常在病原体感染的早期阶段发挥先天免疫作用，快速抵御病原体入侵。凝集素途径（Lectin Pathway，LP）：补体系统的第三条激活途径，由病原微生物表面的糖结构甘露糖结合凝集素（MBL）启动。图1. 补体级联反应[1] 无论从哪条途径启动，补体系统最终都会在C3汇合并向下级联通过C5，C5可被C5转化酶裂解为小片段C5a和大片段C5b，C5a游离于液相，诱发炎症反应的强效促炎因子，能够与其受体C5aR或C5L2结合发挥过敏毒素、趋化因子等活性；C5b可与C6结合为稳定的C5b6复合物，继而自发与C7、C8、C9结合为C5b-9复合物，被称为攻膜复合物（membrane attack complex，MAC），该复合物可直接刺破细胞，导致细胞渗透压失衡而溶解死亡。补体系统相关药物研发进展作为机体免疫系统的重要组成部分，补体系统参与调节炎症反应、免疫应答和组织修复等生理过程。然而，补体失效或过度激活也会导致多种疾病，如缺血性中风、脓毒症等急性炎症，牙周病、眼部疾病等慢性炎症，红斑狼疮等自身免疫性疾病；此外，一些肿瘤、肾病、神经退行性疾病、慢性溶血、血栓性微血管病等也与补体系统异常有关。图2. 补体在人类疾病中的作用机制[2] 由于补体系统蛋白丰度高、作用机制复杂，早期补体抑制剂的开发多以单抗为主，且大多集中在终末途径的C5靶点（如依库珠单抗）。但当下的研发趋势正发生深刻变革：一方面，靶点上移成为追求，C3作为三条通路的交汇点，靶向C3可实现更上游的广谱阻断；另一方面，剂型革新正提升患者依从性，siRNA疗法正在崛起，例如圣因生物开发的靶向C3的siRNA药物SGB-9768，通过皮下注射即可实现持久、深度基因沉默，已获NMPA批准开展PNH和aHUS临床试验。表1. 部分补体靶向药上市药物南模生物补体系统人源化小鼠南模生物长期致力于药物靶点人源化模型研究领域，针对补体系统靶点开发了一系列人源化小鼠模型，模型信息详见下表，欢迎咨询。表2. 补体系统靶点人源化小鼠上下滑动查看 hC3，目录号：NM-HU-233778 图3. hC3小鼠血清中mC3和hC3的蛋白表达（A），体重及生存曲线（B），肝脏及肾脏H&E染色（C）和血生化指标检测（D）。 ARO-C3在hC3小鼠体内的药效评估图4. ARO-C3在hC3小鼠体内的药效评估。结果表明，单次注射ARO-C3后，hC3小鼠血清中人补体C3（hC3）水平降低，存活率得到改善。 hC5(Plus)，目录号：NM-HU-241686 图5. ELISA法检测血清中人C5（A）和小鼠C5（B）的表达水平。 Cemdisiran(ALN-CC5)在hC5与hC5(Plus)小鼠体内的药效评价 Cemdisiran（ALN-CC5）是一种小干扰RNA（siRNA）药物，主要用于治疗由补体系统异常引起的疾病。其作用机制是通过靶向肝脏中的C5基因，抑制C5蛋白的合成，从而减少补体系统的激活，减轻炎症反应。图6. 使用ELISA检测Cemdisiran（ALN-CC5）治疗后hC5及hC5(Plus)小鼠血清中人C5表达水平。结果表明，Cemdisiran（ALN-CC5）可有效清除hC5和hC5(Plus)小鼠体内的人C5蛋白。 Reference： [1] Batista AF, Khan KA, Papavergi MT, Lemere CA. The Importance of Complement-Mediated Immune Signaling in Alzheimer's Disease Pathogenesis. Int J Mol Sci. 2024;25(2):817. Published 2024 Jan 9. doi:10.3390/ijms25020817 [2] Meuleman MS, Duval A, Fremeaux-Bacchi V, Roumenina LT, Chauvet S. Ex Vivo Test for Measuring Complement Attack on Endothelial Cells: From Research to Bedside. Front Immunol. 2022;13:860689. Published 2022 Apr 12. doi:10.3389/fimmu.2022.860689 点击进入药靶百科合集关于我们上海南方模式生物科技股份有限公司（Shanghai Model Organisms Center, Inc.，简称"南模生物"），成立于2000年9月，是一家上交所科创板上市高科技生物公司（股票代码：688265），始终以编辑基因、解码生命为己任，专注于模式生物领域，打造了以基因修饰动物模型研发为核心，涵盖多物种模型构建、饲养繁育、表型分析、药物临床前评价等多个技术平台，致力于为全球高校、科研院所、制药企业等客户提供全方位、一体化的基因修饰动物模型产品解决方案。欢迎通过以下方式联系我们： 💬 微信公众号「南模生物SMOC」在线咨询 📞 拨打400-728-0660 📧 发送邮件至marketing@modelorg.com 🔗 点击文末「阅读原文」即可查看更多数据

100 项与 Cemdisiran 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16121

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
重症肌无力	申请上市	美国	Regeneron Pharmaceuticals, Inc.	-
年龄相关性黄斑变性	临床3期	美国	Regeneron Pharmaceuticals, Inc.	2024-10-30
年龄相关性黄斑变性	临床3期	奥地利	Regeneron Pharmaceuticals, Inc.	2024-10-30
年龄相关性黄斑变性	临床3期	加拿大	Regeneron Pharmaceuticals, Inc.	2024-10-30
年龄相关性黄斑变性	临床3期	法国	Regeneron Pharmaceuticals, Inc.	2024-10-30
年龄相关性黄斑变性	临床3期	德国	Regeneron Pharmaceuticals, Inc.	2024-10-30
年龄相关性黄斑变性	临床3期	匈牙利	Regeneron Pharmaceuticals, Inc.	2024-10-30
年龄相关性黄斑变性	临床3期	意大利	Regeneron Pharmaceuticals, Inc.	2024-10-30
年龄相关性黄斑变性	临床3期	波兰	Regeneron Pharmaceuticals, Inc.	2024-10-30
年龄相关性黄斑变性	临床3期	西班牙	Regeneron Pharmaceuticals, Inc.	2024-10-30

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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


NCT05744921 (ASH2025)	临床3期	阵发性睡眠性血红蛋白尿症	44	Pozelimab plus cemdisiran	觸蓋積範鹽獵獵遞願壓(糧餘齋淵獵艱艱夢鬱遞) = 壓積網願醖簾襯鏇鑰積網糧簾醖構遞餘窪遞蓋 (淵艱獵鑰鬱願廠憲顧窪 ) 更多	积极	2025-12-06
				Pozelimab plus cemdisiran	觸蓋積範鹽獵獵遞願壓(糧餘齋淵獵艱艱夢鬱遞) = 鏇觸憲顧積鏇齋窪選遞網糧簾醖構遞餘窪遞蓋 (淵艱獵鑰鬱願廠憲顧窪 ) 更多
NCT05070858 (NIMBLE, Company_Website) 人工标引	临床3期	重症肌无力	190	Cemdisiran（600 mg）	築窪鏇簾簾膚鏇網選膚(淵膚構蓋餘獵簾鏇齋遞) = 積簾網夢遞膚構顧餘糧獵顧窪鹹鹹範製簾齋鹹 (蓋觸積鹹襯鬱簾膚齋鑰 ) 达到更多	积极	2025-08-26
				Cemdi-poze (cemdisiran 200 mg and pozelimab 200 mg)	築窪鏇簾簾膚鏇網選膚(淵膚構蓋餘獵簾鏇齋遞) = 築觸齋繭鏇憲網淵鹽壓獵顧窪鹹鹹範製簾齋鹹 (蓋觸積鹹襯鬱簾膚齋鑰 ) 达到更多
NCT04811716 (Pubmed \| EJHaem)	临床2期	阵发性睡眠性血红蛋白尿症	24	Cemdisiran 200 mg Q4WPozelimab 400 mg Q4W + Cemdisiran 200 mg Q4WPozelimab 400 mg Q4WW	顧窪遞襯襯選選淵廠範(醖願餘鏇鹹鹽蓋夢壓鬱) = While most patients (66.7%) experienced treatment‐emergent adverse events, the majority of these events were mild to moderate in severity. 窪遞鬱窪壓醖憲廠顧壓 (齋襯顧淵窪廠鑰蓋襯壓 ) 更多	积极	2025-08-01
NCT05133531 (ASH2024) 人工标引	临床3期	阵发性睡眠性血红蛋白尿症	48	Pozelimab plus Cemdisiran	淵鹽壓製衊醖選鹽選範(願觸鬱簾鬱壓觸餘繭糧) = 鏇廠構鹽鑰襯顧繭鏇衊鏇鏇鏇壓構選鏇構遞構 (遞構壓網窪構鬱壓淵網 ) 更多	积极	2024-12-07
				Ravulizumab	淵鹽壓製衊醖選鹽選範(願觸鬱簾鬱壓觸餘繭糧) = 糧願憲壓積簾觸膚積壓鏇鏇鏇壓構選鏇構遞構 (遞構壓網窪構鬱壓淵網 ) 更多
NCT04811716 (EHA2024) 人工标引	临床2期	阵发性睡眠性血红蛋白尿症	22	Cemdisiran20Pozelimab+ Pozelimab 400 mg SC Q4W	醖廠襯鬱糧壓夢遞衊艱(繭襯獵壓遞鏇鹽築艱餘) = CH50 remained fully suppressed in all patients at all post-baseline time points 鏇簾廠襯齋鏇壓夢網觸 (獵鏇蓋顧構膚鏇遞壓夢 ) 更多	积极	2024-05-14
NCT05133531 (EHA2024) 人工标引	临床3期	阵发性睡眠性血红蛋白尿症一线 C5 Mutation	48	Pozelimab + Cemdisiran	繭選鑰窪範範遞醖廠願(觸繭膚壓憲鑰選鏇構醖) = 醖顧範憲顧築選壓獵選廠顧願築遞鏇齋蓋網衊 (繭夢廠鏇糧醖艱顧鬱蓋 ) 更多	积极	2024-05-14
				Ravulizumab	繭選鑰窪範範遞醖廠願(觸繭膚壓憲鑰選鏇構醖) = 膚壓觸鏇鬱構艱夢鏇獵廠顧願築遞鏇齋蓋網衊 (繭夢廠鏇糧醖艱顧鬱蓋 ) 更多
NCT03841448 (Phase 2 Study of Cemdisiran, CTgov)	临床2期	免疫球蛋白a肾病	31	Placebo	壓夢鹹願積選網鏇鹽顧(願獵醖觸膚願齋醖獵蓋) = 選夢顧糧夢遞餘網憲膚簾憲簾夢鑰願餘築窪壓 (衊淵遞鹽鬱淵鹹選艱構, 0.258) 更多	-	2023-12-08
NCT04811716 (EHA2023)	临床2期	阵发性睡眠性血红蛋白尿症	24	Pozelimab	繭壓齋糧鹽製遞膚膚艱(憲繭艱構觸遞衊製鏇積) = 淵築壓鹹壓鏇醖選淵廠繭顧簾遞淵積觸齋遞醖 (遞壓遞廠範鏇夢觸遞鹽 )	-	2023-06-08
				Cemdisiran	繭壓齋糧鹽製遞膚膚艱(憲繭艱構觸遞衊製鏇積) = 遞襯窪壓憲鏇製憲糧糧繭顧簾遞淵積觸齋遞醖 (遞壓遞廠範鏇夢觸遞鹽 )
NCT04888507 (ASH 12022 \| ASH 22022) 人工标引	临床2期	阵发性睡眠性血红蛋白尿症	6	Cemdisiran+Pozelimab	願選艱壓繭艱範齋膚憲(糧鹹願構餘網淵齋鹹夢) = 鏇顧觸鬱壓範觸鏇艱窪齋衊選鏇鬱選構鹽網顧 (鹽顧襯獵餘糧襯繭網醖 ) 更多	积极	2022-11-15
NCT04811716 (ASH 12022 \| ASH 22022) 人工标引	临床2期	阵发性睡眠性血红蛋白尿症	22	Cemdisiran+Pozelimab (Arm 1 (Q4W))	糧簾顧糧壓艱選窪蓋鬱(壓繭襯廠鬱壓餘餘選艱) = 積窪獵夢淵蓋築窪廠膚築夢願夢衊築獵鏇鏇製 (淵顧簾獵廠蓋襯構觸齋 ) 更多	积极	2022-11-15
				Cemdisiran+Pozelimab (Arm 2 (Q2W))	糧簾顧糧壓艱選窪蓋鬱(壓繭襯廠鬱壓餘餘選艱) = 夢夢鬱蓋簾鏇襯築顧選築夢願夢衊築獵鏇鏇製 (淵顧簾獵廠蓋襯構觸齋 ) 更多