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更新于：2025-07-14

Cemdisiran

更新于：2025-07-14

概要

概要

基本信息

药物类型

siRNA

别名

AD-62643、ALN-62643、ALN-CC5

靶点

作用方式

抑制剂

作用机制

C5抑制剂(补体C5抑制剂)

治疗领域

肿瘤免疫系统疾病神经系统疾病+ [6]

在研适应症

年龄相关性黄斑变性地图样萎缩阵发性睡眠性血红蛋白尿症+ [4]

非在研适应症

非典型溶血性尿毒症综合征

原研机构

Alnylam Pharmaceuticals, Inc.

在研机构

Regeneron Pharmaceuticals, Inc.

Curia, Inc

再鼎医药（上海）有限公司

+ [1]

非在研机构

Curiato, Inc.

权益机构

Regeneron Pharmaceuticals, Inc.

Alnylam Pharmaceuticals, Inc.

最高研发阶段临床3期

首次获批日期-

最高研发阶段(中国)临床3期

特殊审评孤儿药 (美国)、孤儿药 (欧盟)

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结构/序列

使用我们的RNA技术数据为新药研发加速。

或

查看完整样例数据

Sequence Code 32355856

来源: *****

Sequence Code 1103240105

来源: *****

关联

项与 Cemdisiran 相关的临床试验

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.

NCT06479863

/ Recruiting早期临床1期IIT

Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Sporadic Inclusion Body Myositis

To evaluate the efficacy of Pozelimab/Cemdisiran combination therapy in patients with sIBM

开始日期2024-08-08

申办/合作机构

Regeneron Pharmaceuticals, Inc.

NCT05131204

/ Terminated临床3期

A Randomized, Open-Label, Eculizumab and Ravulizumab Controlled Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Are Currently Treated With Eculizumab or Ravulizumab

The primary objective of the study is:
To evaluate the effect of pozelimab and cemdisiran combination therapy on hemolysis, as assessed by lactate dehydrogenase (LDH), after 36 weeks of treatment, in patients with PNH who switch from eculizumab or ravulizumab therapy versus patients who continue their eculizumab or ravulizumab therapy
The secondary objectives of the study are to:
* Evaluate the effect of pozelimab and cemdisiran combination treatment versus anti-C5 standard-of-care treatment (eculizumab or ravulizumab) on the following:
* Transfusion requirements and transfusion parameters
* Measures of hemolysis: LDH control, breakthrough hemolysis, and inhibition of CH50
* Hemoglobin levels
* Fatigue as assessed by Clinical Outcome Assessments (COAs)
* Health-related quality of life (HRQoL) as assessed by COAs
* Safety and tolerability
* To assess the concentrations of total pozelimab and either total eculizumab or total ravulizumab in serum and total cemdisiran and total C5 protein in plasma
* To assess the immunogenicity of pozelimab and cemdisiran

开始日期2022-10-06

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）

2024-05-01·International journal of laboratory hematology

Complement inhibition in paroxysmal nocturnal hemoglobinuria: From biology to therapy

Review

作者: Fattizzo, Bruno ; Versino, Francesco

Abstract:

Complement inhibitors are the mainstay of paroxysmal nocturnal hemoglobinuria (PNH) treatment. The anti‐C5 monoclonal antibody eculizumab was the first treatment to improve hemolysis, thrombotic risk, and survival in PNH although at the price of a life‐long intravenous fortnightly drug. Additionally, suboptimal response may occur in up to 2/3 of patients with persistent anemia due to incomplete control of intravascular hemolysis, development of upstream C3‐mediated extravascular hemolysis (EVH), or concomitant bone marrow failure. Ravulizumab, a longer half‐life anti‐C5 developed from eculizumab, administered every 8 weeks, improved patient convenience, and reduced pharmacokinetic breakthrough hemolysis (BTH) by establishing more stable anti‐C5 concentrations. More recently, several other anti‐C5 compounds (crovalimab, pozelimab, tesidolumab, cemdisiran, zilucoplan, and coversin) are on study in clinical trials. Upstream inhibition of complement cascade was also explored with the anti‐C3 pegcetacoplan, and with the alternative pathway inhibitors iptacopan (anti‐factor B) and danicopan (anti‐factor D). These drugs efficiently target EVH and are able to improve anemia and transfusion need in suboptimal responders to anti‐C5. The route and schedule of administration (twice weekly subcutaneously for pegcetacoplan and twice or thrice oral daily dosing for iptacopan and danicopan, respectively) are very convenient but pose novel issues regarding adherence. Additionally, both anti‐C5 and upstream inhibitors do not resolve the unmet need of pharmacodynamic BTH events due to complement amplifying conditions such as infections, traumas, and surgery. In this review, we will recapitulate PNH physiopathology, clinical presentation, and diagnosis and describe available and developing drugs that will lead to a precision medicine approach for this rare though heterogenous disease.

2024-04-01·Clinical journal of the American Society of Nephrology : CJASN

Phase 2 Trial of Cemdisiran in Adult Patients with IgA Nephropathy: A Randomized Controlled Trial

Article

作者: Bhan, Ishir ; Wang, Dazhe ; Villanueva, Russell ; Fernström, Anders ; Badri, Prajakta ; Barbour, Sean J. ; Borodovsky, Anna ; Cattran, Daniel ; Sperati, C. John ; Liew, Adrian ; Wu, Ming-Ju ; Yureneva, Elena ; Barratt, Jonathan ; Yeo, See Cheng

Background:

IgA nephropathy is the most common primary GN. Clinical features of IgA nephropathy include proteinuria, which is the strongest known surrogate of progression to kidney failure. Complement pathway activation is a critical driver of inflammation and tissue injury in IgA nephropathy. Cemdisiran is an investigational RNA interference therapeutic that suppresses hepatic production of complement component 5 (C5), thereby potentially reducing proteinuria in IgA nephropathy. We evaluated the efficacy and safety of cemdisiran in adult patients with IgA nephropathy at high risk of kidney disease progression.

Methods:

In this phase 2, 36-week, double-blind study, adult patients with IgA nephropathy and urine protein ≥1 g/24 hours were randomized (2:1) to subcutaneous cemdisiran 600 mg or placebo every 4 weeks in combination with the standard of care. The primary end point was percentage change from baseline at week 32 in urine protein-to-creatinine ratio (UPCR) measured by 24-hour urine collection. Additional end points included change from baseline in UPCR measured by spot urine, serum C5 level, and safety assessments.

Results:

Thirty-one patients were randomized (cemdisiran, N=22; placebo, N=9). Cemdisiran-treated patients had a placebo-adjusted geometric mean change in 24-hour UPCR of –37.4% (cemdisiran-adjusted geometric mean ratio to baseline [SEM], 0.69 [0.10]) at week 32. Spot UPCR was consistent with 24-hour UPCR placebo-adjusted change of –45.8% (cemdisiran-adjusted geometric mean ratio to baseline [SEM], 0.73 [0.11]). Mean (SD) change in serum C5 level from baseline at week 32 was –98.7% (1.2) with cemdisiran and 25.2% (57.7) with placebo. Over 36 weeks, most adverse events were mild or moderate and transient; the most common adverse event after cemdisiran treatment was injection-site reaction (41%).

Conclusions:

These findings indicate that treatment with cemdisiran resulted in a reduction of proteinuria at week 32 and was well tolerated.

2023-12-04·Clinical kidney journal

Targeting complement in IgA nephropathy

Review

作者: Gutiérrez, Eduardo ; Caravaca-Fontán, Fernando ; Sevillano, Ángel M ; Praga, Manuel

ABSTRACT:

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Recent years have witnessed significant improvements in the understanding of the pathogenesis of IgAN and particularly, the pathogenic role of complement activation. The alternative complement pathway is the major complement cascade activator in IgAN, and glomerular C3 deposition has been shown to correlate with disease progression. In addition, several studies have provided insight into the pathogenic role of factor H–related proteins -1 and -5 in IgAN, as independent players in complement dysregulation. The lectin pathway has also been shown to be associated with the severity of IgAN. Glomerular deposition of C4d has been associated with increased histologic disease activity, faster decline in estimated glomerular filtration rate and higher risk of kidney failure. On the other hand, although overlooked in the Oxford classification, numerous studies have shown that the coexistence of thrombotic microangiopathy in IgAN is a significant indicator of a poorer prognosis. All the breakthroughs in the understanding of the contributing role of complement in IgAN have paved the way for the development of new complement-targeted therapies in this disease. Several ongoing trials are evaluating the efficacy of new agents against factor B (iptacopan, Ionis-FB-LRX), C3 (pegcetacoplan), factor D (vemircopan, pelecopan), C5 (ravulizumab, cemdisiran) and C5a receptor 1 (avacopan). In this study, we provide a comprehensive review of the role of complement in IgAN, including the emerging mechanisms of complement activation and the promising potential of complement inhibitors as a viable treatment option for IgAN.

项与 Cemdisiran 相关的新闻（医药）

2025-07-13

·抗体圈

siRNA药物开发的三个“E”挑战

摘要：siRNA治疗方法已获得广泛关注，目前已有六种siRNA获准用于临床应用。尽管它们被研究用于治疗代谢、心血管、传染性和罕见遗传疾病，以及癌症和中枢神经系统（CNS）疾病，但依然存在几个药物可用性挑战。在这里，我们提供有关这些挑战的深入讨论，包括靶向积累和细胞摄取（‘进入’）、内溶酶体逃逸（‘逃逸’）以及体内药效表现（‘疗效’）——这三个‘E’挑战，同时也阐明siRNA药物开发。此外，我们提出几种有前景的策略，这些策略在促进siRNA治疗药物临床转化方面具有巨大潜力，包括探索多样的配体-siRNA结合物、扩大潜在疾病靶点，以及开掘新的修饰几何形状，以及开发组合疗法。文章亮点：1.理论上，siRNA能够靶向任何感兴趣的基因，潜在地解决那些对小分子和蛋白质而言‘无法药物化’的疾病靶标。2.目前，已有六种siRNA治疗药物获得临床使用批准，以及大约20种其他候选药物已进入临床研究的后期阶段。3.靶向累积和细胞摄取（进入）、内溶酶体逃逸（逃避）以及体内药理学性能（疗效）（三个‘E’挑战）是siRNA药物开发中最关键的瓶颈。4.配体缀合的siRNA是有前景的平台，已经在强健的肝外递送方面取得了突破。复杂且适当的化学修饰可能会在siRNA方式的稳定性和长期疗效方面带来惊人的突破。【NO.1】siRNA治疗的蓬勃发展从制药历史的角度来看，小分子药物作为最早开发和应用的治疗方式，享用了超过一个世纪的使用，而蛋白质和抗体相对较晚出现，并且研究了将近半个世纪。尽管核酸分子作为一种新型治疗方法的发展时间较短（20-30年），但它们已经引起了制药行业的显著全球关注，成为第三种最显著的治疗方式。核酸药物仍在快速探索和开发中，特别是在RNAi领域，其广泛而深远的治疗潜力日益显现。考虑到这一点，我们相信即将到来的时期将是核酸的一个关键时代，既扩大了治疗选择的范围，也为该领域提供了新可能性。与传统的小分子药物和抗体相比，siRNA（见词汇表）具有丰富的疾病靶点、高开发成功率、短开发时间、强大且持久的疗效，以及平台化模式的卓越特征。目前，六种siRNA药物（patisiran、givosiran、lumasiran、inclisiran、vutrisiran和Rivfloza）已成功商业化。尽管siRNA药物在临床实践中的应用前景广泛，但其开发面临关键挑战，包括靶向积累和细胞摄取（进入）、内溶酶体逃逸（逃逸）和体内药效（疗效）（三大“E”挑战）。在本文中，我们阐述了siRNA治疗的当前状态和未来前景，概括了该领域所遇到的关键挑战，并提出了一系列应对策略。通过提供广泛的见解和灵感，本文旨在为科学和制药界提供有价值的指导。【NO.2】siRNA疗法的最新研究和开发状态近年来，siRNA疗法在多个候选药物的前临床和临床研究开发中显示出了巨大的潜力。截至2023年8月，全球范围内有15种在临床二期或后期阶段的研究siRNA药物（表1），涵盖广泛的治疗领域，包括罕见疾病和遗传性疾病，并扩展到常见疾病。主要制药公司已扩大其研究重点，以涵盖代谢性疾病、心血管疾病、乙型肝炎和癌症等常见病。例如，ALN-AGT（NCT04936035i，NCT05103332ii，随机）目前正在开发中，用于治疗高血压，并已进入二期临床试验。Olpasiran（NCT05581303iii，随机）旨在治疗动脉粥样硬化斑块，正在进行三期研究。SLN360（NCT05537571iv，随机）是一种降脂siRNA，已进入二期研究。RBD1016（NCT05961098v，随机）是一种用于治疗乙型肝炎的N-乙酰半乳糖胺（GalNAc）结合siRNA，将在欧洲开始二期试验。STP705和STP707由两种siRNA组成，靶向转化生长因子β1（TGF-β1）和环氧合酶2（COX-2），并以肽纳米粒（PNPs）形式制备。STP705局部施用到病变组织中，以治疗原位鳞状细胞癌（isSCC）（NCT04844983vi，二期，随机）和基底细胞癌（BCC）（NCT04669808vii，二期，非随机），而STP707（NCT05037149viii，一期，非随机）则通过静脉注射到身体中，用于治疗几种实体瘤和纤维化肝病，例如原发性硬化性胆管炎（PSC）。表1.选定的商业化或晚期研究的siRNA疗法从产品管道的角度来看，siRNA疗法的一个显著突破在于其扩展到肝外疾病，包括小分子药物和抗体药物一直未能涉足的领域，如中枢神经系统疾病。ALN-APP（NCT05231785ix，第一阶段，随机）是一种经椎管内给药的siRNA，靶向淀粉样前体蛋白（APPs），用于治疗阿尔茨海默病（AD）和脑淀粉样血管病（CAA）。最近，ALN-APP的第一阶段研究在单药剂量递增试验中获得了积极的中期结果。ARO-SOD1（NCT05949294xi，第一阶段，随机）是一种针对中枢神经系统内超氧化物歧化酶1（SOD1）的研究性siRNA，可能用于治疗由SOD1突变引起的肌萎缩侧索硬化症（ALS），目前正在进行第一阶段研究。此外，临床开发的RNAi疗法正在向将siRNA递送到其他组织（如眼睛、肌肉、肺部和脂肪）迈进。Tivanisiran（SYL1001）（NCT03108664xii，NCT04819269xiii，随机）目前正在进行第三阶段临床研究，以治疗干眼症。ARO-DUX4（第一/第二阶段）用于治疗面肩肱肌营养不良（FSHD）已提交临床试验。ARO-MUC5AC（NCT05292950xv，第一阶段，随机）、ARO-RAGE（NCT05276570xvi，第一阶段，随机）和ARO-MMP7（NCT05537025xvii，第一/二a阶段，随机）目前正在研究用于治疗肺部疾病。值得注意的是，siRNA的给药频率已经实现了历史性的突破。siRNA的增强稳定性修饰使其能够在体内持久抑制基因和治疗效果，同时避免潜在的序列依赖性非特异性效果。例如，Leqvio在头三个月只需给药两次，随后每六个月治疗一次，以有效管理原发性高胆固醇血症或混合性脂质异常。目前，全球有超过100家公司从事siRNA领域，其中大约30家公司专注于siRNA药物开发。根据Informa Pharma Intelligence的生物追踪记录，目前大约有200种基于siRNA/RNAi的药物正在进行临床前和临床研究。自2016年以来，共有14种siRNA和反义寡核苷酸（ASO）获得批准商业化。此外，寡核苷酸治疗领域在并购方面也见证了显著活动。近年来，在心血管和代谢疾病、神经系统疾病和乙型肝炎等领域有一些值得注意的许可协议。代表性的siRNA递送平台包括脂质纳米颗粒（LNP）、GalNAc-siRNA偶联物（GalAheadTM、PDoV-GalNAc等）、GEMINI、™TRiM™、PNP、RIBO-GalSTAR®和RIBO-OncoSTAR，而IKARIA™的建立是为了开发长效siRNA。【NO.3】siRNA临床研究的瓶颈尽管siRNA药物研究取得了重大进展，但仍存在一些需要克服的关键挑战。具体来说，三个“E”挑战（进入、逃逸、疗效）是限制siRNA临床翻译和应用的三个关键问题。图1.限制siRNA临床翻译和应用的三个“E”挑战3.1进入挑战：靶向积累和细胞摄取第一个挑战是在靶器官/组织中实现siRNA的高效富集并有效内化到靶细胞中（图1A）。由于它们的大尺寸和阴离子电荷，未修饰的裸siRNA显示出低生物利用度，半衰期短至几分钟。纳米载体封装的siRNA通常与血清蛋白结合，导致网状上皮系统（RES）摄取和吞噬清除。此外，siRNA可被血浆、组织和细胞质中存在的核酸酶或磷酸酶快速降解。全身清除后，siRNA必须穿过毛细血管的内皮才能进入组织，由于广泛的粘附和紧密连接，这尤其具有挑战性。尽管siRNA可能被动地积累在肝脏或肿瘤组织等多孔部位，但将这些治疗剂输送到优先吸收这些分子的器官以外的身体其他部位，以及血液-脑屏障（BBB）和血液-视网膜屏障等屏障的有效穿越，仍然面临巨大的挑战。3.2逃逸激发试验：内体和溶酶体逃逸第二个挑战是如何实现有效的内体和溶酶体逃逸。虽然siRNA可以通过内吞作用进入细胞，但只有不到1%的siRNA可以从内吞作用中逃逸，被动siRNA逃逸率低于0.01%。去唾液酸糖蛋白受体（ASGPR）是一个明显的例外，其肝细胞表达水平约为500000或更高，循环时间不到20分钟。足够的GalNAc-siRNA偶联物可以在肝细胞的细胞质中积累，以在治疗期间达到治疗水平。虽然这为未来基于RNAi的肝脏治疗靶向带来了希望，但siRNA逃逸对于其他类型的细胞来说仍然是一个未解决的问题。大多数表面受体的表达范围为10000–100000或更短，受体回收时间大约或超过90分钟（图1B）。由于细胞质和内体中siRNA的降解，观察到在任何给定时刻，只有极小的内吞GalNAc-siRNA偶联物存在于体内细胞质中。值得注意的是，虽然内体包埋的RNA治疗药物起到了作用，从而维持了较长的单剂量反应持续时间，但这一优势被很大一部分无法穿透细胞质的内吞RNA治疗药物所抵消。因此，虽然内体的释放确实是抑制RNA疗法在人类疾病治疗中更广泛应用的主要障碍，但值得注意的是，需要有一种平衡，以在一定程度上维持贮存效应，确保长时间的持续反应。迄今为止，试图使用改良的pH敏感性、离子穿透剂、氯喹样溶酶体试剂、成孔肽如蜂毒肽、十二烷基磷酸胆碱（DPC）和/或GalNAc偶联的蜂毒肽样肽（NAG-MLP）来增强内体逃逸，但尚未完全解决细胞毒性与内体逃逸增加之间的关系。3.3疗效挑战：体内药物性能第三个挑战是要求良好的体内稳定性、持久效果和安全性。使用病毒载体进行体内核酸递送有一些毒副作用和目前主要限于临床前研究。化学合成的载体系统，如阳离子脂质和大多数无机纳米颗粒，可在体内诱导细胞凋亡和炎症。给药系统还必须确保生产、质量控制和运输的便利性，以实现大规模临床应用。此外，目前RNA药物临床前研究中广泛使用的小鼠模型并不是毒性评价模型，因为从小鼠模型获得的RNA剂量反应关系不能直接应用于人类。非灵长类动物模型通常缺乏与人类的基因组序列的足够重叠来预测药效学效应，因此有必要扩大非人灵长类动物（NHP）模型的使用，或者作为潜在的选择，扩大与疾病相关的类器官的使用。未经修饰的寡核苷酸通常在体内不稳定，并且很容易被血液中的核酸酶降解。此外，外源寡核苷酸可能在体内显示免疫原性并引起免疫反应。随着技术的突破，化学修饰【例如，对硫代磷酸盐（PS）骨架、核糖和链末端的修饰】已被广泛用于增强siRNA的稳定性，减少/消除脱靶效应和免疫原性，从而提高siRNA的“功效”（图1C）。通过复杂的修饰，siRNA已成功实现99%的基因沉默并在体内持续存在，允许低剂量季度、半年甚至每年给药。化学修饰的进化史及其对siRNA功效的影响是一个令人着迷的研究领域，值得进一步全面探索。然而，尽管取得了这些可喜的成就，但仍存在一些挑战。例如，修饰诱导的稳定性和特异性增强可能会降低沉默活性或引起意想不到的不良反应（图1D）。此外，在临床前和临床研究中，都需要仔细评估siRNA的免疫原性和毒性（包括脱靶诱导毒性）。更重要的是，一系列专利家族对siRNA药物开发的知识产权格局做出了重大贡献。例如，WO2016028649概述了一种几何结构，该几何结构将siRNA的两条链的修饰划分为由核苷酸计数的特定范围定义的不同区域，从而提供每个区域的修饰单体的化学结构或物理化学性质。WO2013074974描述了一种dsRNA双链体，其基序由一条或两条链中三个连续核苷酸上的三个相同修饰组成，特别是在切割位点附近。此外，WO2018185241重点介绍了反义链5'端2位和14位核苷酸的修饰策略，以及正义链上的核苷酸，对应于反义链的11、13、11和13或11-13位。这些专利对siRNA药物开发构成了重大障碍，必然需要该领域的其他实体建立独特的技术。【NO.4】克服三个“E”挑战的有前途的策略为了应对这些挑战并推动siRNA疗法的发展，几种有前途的策略或方法值得探索。图2.克服三个“E”挑战的有前途的方法4.1开发新型化学修饰优化化学修饰是提高siRNA稳定性、特异性、安全性和生物利用度的重要方向。这包括开发新的化学修饰单体、修饰模式和RNAi触发结构（图2A-C）。传统的siRNA修饰主要涉及2′-O-甲基化（2′-OMe）、2′-氟脱氧核糖核苷酸（2′-F）和PS，而新型修饰单体和修饰模式的开发将进一步完善siRNA的药代动力学和安全性。例如，已经开发了新型单体，如乙二醇核酸（GNA）和5′-（E）-乙烯基膦酸盐[5′-（E）-VP]（图2B），新型修饰模式，如增强稳定化学（ESC）plus（ESC+）（图2A），以及新型RNAi触发结构，如小环状干扰RNA（sciRNA）、不对称siRNA和二价siRNA支架（图2C）。此外，现在可以使用算法实现siRNA的设计和修饰。例如，Alnylam已经开发了几代siRNA设计，包括部分修饰的标准模板化学（STC）、ESC、高级ESC、ESC+和IKARIA™。几种ESC+偶联物目前正处于临床流程中。在专利方面，新型单体、图案和结构的发展可以为新来者提供绕过现有知识产权的空间。此外，业务合作期间的开放许可协议可以为其他公司提供使用siRNA技术的机会，促进其普及和商业化。4.2建立独特的递送系统虽然LNP、聚合物、无机纳米颗粒和外泌体等各种纳米材料已被开发为siRNA载体，但它们的负载能力、稳定性、安全性和有效性仍然存在局限性。未来的基础研究应侧重于优化这些载体的物理化学性质，并使用独特的靶向配体或化学部分特异性结合患病细胞的表面标志物/受体。siRNA可以与配体共价连接以形成配体-siRNA偶联物，这可以降低循环中的清除率并增强靶向积累和细胞摄取，从而调节其药代动力学和药效学特征。这些配体包括小分子、脂质[如胆固醇、2′-O-十六烷基（C16）、各种脂肪酸]、肽（如RGD衍生物、H2009.1、A20FMDV2、胱氨酸结肽）、适配体、抗体、蛋白质（如centyrin）、糖类（如GalNAc）和非编码RNA（ncRNA）（图2D）。与纳米颗粒相比，配体偶联物通常体积小，易于大规模合成，并具有明显的药代动力学特性。与脂肪酸等脂质部分结合可以改变肝外组织中的积累，从而能够在包括CNS、心脏、肺和肌肉在内的多种组织中进行基因调控。抗体和细胞表面受体之间的特异性相互作用可能能够递送到其他技术无法到达的特定组织和/或细胞亚群。单剂量的TfR1抗体（αTfR1）与siRNA偶联，在小鼠和猴子中产生超过75%的mRNA减少，骨骼肌和心脏（横纹）肌的沉默最严重，而其他主要器官的沉默活动最少或没有。siRNA治疗药物还可以与阳离子肽部分（如细胞穿透肽和Endo-Porter）连接，有效穿透组织屏障和细胞膜。此外，siRNA和内体逃逸增强佐剂的组合可能是将配体偶联的siRNA递送至非肝组织的可行策略。4.3扩大疾病目标siRNA技术主要用于目标蛋白质编码基因。然而，最近的研究表明，ncRNA，如长ncRNA（lncRNA），在各种疾病中起着重要作用（图2E）。因此，开发能够有效调节ncRNA表达的新型RNA靶向技术可能为疾病治疗提供更广泛的机会。此外，探索编码和ncRNA之间的相互作用，例如竞争性内源性RNA（ceRNA）网络，可能会为疾病机制提供新的见解，并实现更有效的治疗干预。除了在mRNA水平调节基因表达外，siRNA技术还可以靶向表观遗传修饰，例如DNA甲基化或组蛋白修饰，这些修饰在疾病的发展和发展中起着至关重要的作用。通过调节表观遗传标记，有可能重编程基因表达模式并逆转疾病表型。4.4探索联合疗法利用双靶向方法或将siRNA与其他治疗药物（如化疗药物、抗体或免疫调节剂）联合使用，有望增强疗效、克服耐药性和减少脱靶效应。这些策略可能为治疗以前无法治愈的疾病创造新的机会。例如，正在实施一种涉及VIR-2218（GalNAc-siRNA偶联物，也称为ALNHBV02）和聚乙二醇-干扰素α(PEG-IFN-α)的联合治疗，旨在实现乙型肝炎的功能性治愈。siRNAJNJ-73763989（JNJ-3989）加核苷（t）类似物（NA）用于评估有/没有衣壳组装调节剂JNJ-56136379（JNJ-6379）的慢性乙型肝炎患者的治疗效果。此外，pozelimab（补体C5靶向抗体）和cemdisiran（一种GalNAc-siRNA偶联物）正在联合用于治疗重症肌无力和阵发性睡眠性血红蛋白尿症（PNH）。此外，正在进行Empaveli（一种环肽）和siRNA组合的临床前研究，这可能会降低Empaveli的治疗频率和/或提高治疗效果。【NO.5】总结和未来展望我们正在见证RNA药物治疗新时代的到来。RNA疗法基于一个强大且多功能的平台，该平台在解决未满足的临床需求方面具有几乎无限的潜力。因此，RNA疗法注定会改变许多疾病的护理标准。随着第六种siRNA药物Rivfloza的获批，未来几年肯定会有更多的siRNA疗法出现。在成功建立用于肝细胞递送的最先进的GalNAc-siRNA偶联物后，肝外递送技术的探索将成为该领域的下一个前沿领域（参见临床医生专区）。与肝脏相比，将RNAi分子递送到靶向非肝脏疾病的挑战要大得多。配体-siRNA偶联物必须以足够的速率在靶细胞中积累以实现沉默。此外，避免同时进行肾脏和网状内皮清除、增强外渗和组织渗透、增加货物内化受体低表达细胞类型的摄取、改善内体逃逸以及支持强效和安全治疗效果等几个因素需要进行珠子处理以实现令人满意的沉默。为了将siRNA的适用性扩大到肝脏组织之外，至关重要的是：（i）识别或确定可以促进有效内化的独特受体;（ii）提出具体的筛选或勘探策略;（iii）设计并鉴定用于稳健递送和持续基因沉默的新型配体;（iv）选择与特定疾病有关的遗传或临床可行的靶基因。如果在临床条件下肝外递送变得可行且稳健，则狩猎RNAi疗法的领域可能会显着扩大。此外，在siRNA的开发中，与化学制造和控制（CMC）以及药物注册政策相关的问题会显著影响新药营销。siRNA的CMC面临多重挑战，包括单体供应、质量控制、能力建设、杂质表征和分离纯化。在药品注册政策方面，目前还缺乏统一的国际标准。建议通过加强科学研究、提高透明度以及修订法规和政策来确保临床试验的安全性和有效性。此外，目前siRNA的主要扩展方向是在慢性疾病领域，如高胆固醇血症、高甘油三酯血症、高血压、高脂蛋白胆固醇（a）[Lp（a）]心血管疾病、非酒精性脂肪性肝炎（NASH）和乙型肝炎。未来siRNA药物开发的突破性方向包括递送至CNS、眼睛、肌肉、肺和脂肪组织和肿瘤。这为siRNA治疗留下了相当大的市场空间。尽管存在挑战（参见悬而未决的问题），但siRNA代表了一种有前途的方式，有可能彻底改变各种疾病的治疗。为了应对与高效和安全递送、内体逃逸、体内功效相关的挑战，其他方面则需要跨多个领域的持续创新和合作。可以肯定的是，经过不懈的努力，这些挑战将继续被规避，并最终迎来进一步的重大突破。识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！请注明：姓名+研究方向！本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

siRNA临床研究

2025-06-17

·医药观澜

寻找“治愈”曙光：7款新药已获批上市，下一代重症肌无力疗法有望迎来新突破

编者按：刚刚过去的“全球重症肌无力关爱日”再次提醒大家关注这一罕见疾病。重症肌无力（MG）是一种罕见的神经肌肉-自身免疫性疾病，会导致患者虚弱和可能危及生命的肌无力。目前该疾病尚无治愈方法。随着研究进展和产业持续投入，近十年来多款针对重症肌无力的创新药获监管机构批准上市，极大改善了患者的生活。与此同时，全球更多MG新药管线已进入临床阶段，涵盖抗体疗法、siRNA药物、小分子、CAR-T疗法等多种类型，有望在不远的未来迎来新突破。作为全球医药及生命科学行业创新的赋能者，药明康德也持续通过一体化、端到端的CRDMO平台，为全球合作伙伴提供赋能，助力重症肌无力等罕见肌肉疾病新药的开发，为患者带来更多突破性的治疗方案。回顾2025年上半年，重症肌无力疾病领域新药再次迎来多项新进展。5月，强生公司（Johnson & Johnson）宣布，美国FDA已批准其抗体疗法Imaavy（nipocalimab）上市，用于治疗抗AChR、抗MuSK抗体阳性的全身性重症肌无力（gMG）成人与12岁以上儿童患者。这是FDA批准的首个用于治疗该类患者群体的新生儿Fc受体（FcRn）阻断剂。这款疗法还被Evaluate列为今年有望上市的10大潜在重磅疗法之一。同月，翰森制药宣布其伊奈利珠单抗（inebilizumab）的新适应症上市申请获得中国NMPA受理，用于治疗全身性重症肌无力成人患者。这是一款靶向CD19 B细胞消耗性抗体，由翰森制药和安进（Amgen）共同开发。该药物的全球关键性3期试验MINT的结果于今年4月发表于《新英格兰医学杂志》。同样是5月，荣昌生物的BLyS/APRIL双靶点融合蛋白创新药物泰它西普在中国获批新适应症，用于治疗全身性重症肌无力成人患者。该产品可同时靶向B细胞激活因子（又称BLyS）和增殖诱导配体（APRIL），针对致病性抗体产生的源头——B细胞及浆细胞。此外，在CAR-T疗法领域，Cartesian Therapeutics于今年4月公布其在研mRNA细胞疗法Descartes-08用于治疗gMG的2b期研究的12个月数据。该研究早前已经取得积极结果，80%的可评估患者维持了临床显著应答达1年。Descartes-08是一款靶向BCMA的在研CAR-T细胞疗法，目前已启动3期临床研究，是MG领域目前研发进度较快的CAR-T细胞疗法，有望成为MG治疗领域首个细胞疗法。从这些进展可以看到，在重症肌无力治疗药物研发领域，2025年正在迎来多元化的新突破。图片来源：123RF过去十年间，至少7款重症肌无力新药获批上市重症肌无力是一种慢性的罕见自身免疫疾病，目前尚无治愈方法。该病的致病机制涉及患者体内的免疫球蛋白G（IgG）抗体，这些抗体会破坏神经与肌肉之间的突触传递，导致肌肉疲劳无力，进而导致极度疲劳和面部表情、言语、吞咽和活动困难，严重时甚至危及生命。大约85%的重症肌无力患者属于全身性重症肌无力（gMG）。根据2021年文献数据，gMG的患病率和发病率在全球范围内正在增加，全球患病率估计为每10万人中有2~36例。过去十年间，全球至少有7款重症肌无力新药获批上市，包括FcRn拮抗剂、补体抑制剂和B细胞耗竭剂等，为MG患者带来了更多治疗选择。C5补体抑制剂包括抗体和大环肽类药物，比如阿斯利康的ravulizumab（瑞利珠单抗）、eculizumab（依库珠单抗），以及优时比公司的大环肽类C5补体抑制剂zilucoplan（泽勒普肽）等，这类药物能够减少补体激活介导的神经肌肉接头损伤；FcRn抑制剂类药物以抗体为主，比如开头提到的强生公司的nipocalimab（尼卡利单抗），以及优时比公司的rozanolixizumab（罗泽利昔珠单抗）、Argenx和再鼎医药共同开发的efgartigimod（艾加莫德）等，它们可降低循环IgG抗体水平，从而减少致病抗体的循环，改善MG症状；B细胞耗竭剂类的代表药物为荣昌生物研发的BLyS/APRIL双靶点融合蛋白泰它西普，针对致病性抗体产生的源头——B细胞及浆细胞，减少致病性自身抗体的产生，发挥治疗作用。寻找“治愈”曙光，下一代重症肌无力疗法有望迎来新突破梳理公开资料可知，除了已获批的新药，全球范围内还有数十款新药正在临床阶段探索用于重症肌无力治疗的潜力，未来有望在多个方向取得新突破。在重症肌无力临床管线中，抗体类药物数量较多，包含单抗、双抗，以及一些抗体融合蛋白等，靶点涉及C5、FcRn、CD19/CD20等。例如阿斯利康在研的第三代C5补体抑制剂抗体gefurulimab已经进入3期临床阶段，其分子量小，具更好的渗透性，有望开发成为一款每周一次、由患者自行给药的皮下注射疗法。再如开头提到的抗CD19单抗伊奈利珠单抗，其翰森制药提交的针对重症肌无力的上市申请已获得中国NMPA受理，安进在两个月前也宣布了该产品治疗gMG成年患者的疗效与安全性的最新临床数据：每年两次给药的情况下，其在乙酰胆碱受体自身抗体阳性（AChR+）gMG患者中具有持久的疗效。CAR-T疗法也在临床研究中展现出“治愈”重症肌无力的潜力。CAR-T疗法近年来在自身免疫性疾病领域进展迅速，其可以使患者实现长期无药物缓解，被认为有望对重症肌无力的治疗产生潜在变革作用。在重症肌无力临床管线中，包括了十多款CAR-T疗法。这些在研管线以靶向B细胞或浆细胞为主，主要包括BCMA和CD19。在MG临床研发管线中，也有多款小分子药物。例如诺华在研的补体B因子口服抑制剂iptacopan（伊普可泮）和BTK抑制剂remibrutinib（瑞米布替尼），目前均已进入重症肌无力治疗研究3期临床阶段。再如NMD Pharma在研的氯离子通道（ClC-1）抑制剂NMD670正处于重症肌无力2b期临床阶段，该产品作用机制是针对骨骼肌的非免疫调节。多肽和核酸药物研发管线也有新突破。泽勒普肽（zilucoplan）作为首个获FDA批准用于治疗重症肌无力的每日一次经皮下给药的新型大环肽类C5补体抑制剂，是肽类药物在这一治疗领域的重要突破。除此之外，siRNA疗法cemdisiran联合抗体疗法pozelimab治疗重症肌无力的临床研究已处于3期阶段。前者由Alnylam公司和再生元（Regeneron）联合开发，作为一种靶向C5补体的RNAi疗法，cemdisiran在进入细胞后通过与靶标mRNA结合，从而使mRNA降解，避免功能性蛋白产生。Pozelimab是再生元开发的新一代C5补体抑制剂，此前已获FDA批准用于CD55缺陷型蛋白丢失性肠病。再生元正在开发这一C5抑制剂“抗体+siRNA”组合疗法以治疗包括重症肌无力在内的补体介导的疾病。其中，cemdisiran可以减少C5的产生，pozelimab可以阻断剩余C5的功能，二者共同抑制终端补体活性，有望在较低剂量下达到完全、持续的C5抑制，减少给药频率，并且皮下给药方便临床应用。值得一提的是，cemdisiran使用的GalNAc递送技术，是当下核酸疗法尤其是siRNA递送到肝细胞的主要策略。迄今FDA批准的7款siRNA疗法中，6款均使用了这项技术。也得益于此类递送技术的持续革新，纵览全球，siRNA疗法研发蓬勃发展，在研管线已超过350款。在这一产业新兴的趋势下，围绕GalNAc等复杂分子，药明康德旗下专注于寡核苷酸和多肽及相关化学偶联药物的WuXi TIDES平台已打造了涵盖定制合成、工艺开发及生产的一站式服务平台，更好地满足全球合作伙伴的寡核苷酸及各类化学偶联物的研发需求。公开信息显示，在定制化GalNAc方面，WuXi TIDES团队已经生产过涵盖不同类型、总数超过100款的GalNAc化合物，覆盖不同类型的GalNAc分子；通过优化GalNAc树脂负载工艺，将固相合成的收率提高50%。同时，借助流动化学平台，加速高纯度GalNAc的规模化生产。在疾病的征程上，科学与技术探索的步伐从未停歇。作为创新的赋能者、客户信赖的合作伙伴以及全球健康产业的贡献者，药明康德也将持续以独特的CRDMO业务模式，助力全球合作伙伴开发包括重症肌无力在内的更多疾病领域的创新疗法，持续造福病患！参考资料：[1]Binks, S.N.M., Morse, I.M., Ashraghi, M. et al. Myasthenia gravis in 2025: five new things and four hopes for the future. J Neurol 272, 226 (2025). https://doi-org.libproxy1.nus.edu.sg/10.1007/s00415-025-12922-7[2]Dresser L., Wlodarski, R., Rezania, K., & Soliven, B. (2021). Myasthenia Gravis: Epidemiology, Pathophysiology and Clinical Manifestations. J Clin Med, 10(11):2235.[3]Bubuioc, A. M., Kudebayeva, A., Turuspekova, S., Lisnic, V., & Leone, M. A. (2021). The epidemiology of myasthenia gravis. Journal of Medicine and Life, 14(1):7-16.版权说明：本文欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权或其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

细胞疗法上市批准免疫疗法临床3期信使RNA

2025-03-18

·PRNewswire

EMPAVELI's Market Success Underscores Growing Demand for Complement Inhibitor Therapies | DelveInsight

EMPAVELI's unique mechanism of targeting C3 broadens its applicability beyond PNH, including other complement-driven diseases like geographic atrophy and immune complex-mediated diseases. With a high unmet need in these areas and limited competition, EMPAVELI's market is poised for steady growth. LAS VEGAS, March 18, 2025 /PRNewswire/ -- DelveInsight's " EMPAVELI Market Size, Forecast, and Market Insight Report" highlights the details around EMPAVELI, a complement inhibitor indicated to treat adult patients with PNH. The report provides product descriptions, patent details, and competitor products (marketed and emerging therapies) of EMPAVELI. The report also highlights the historical and forecasted sales from 2020 to 2034 segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]. Apellis Pharmaceutical's EMPAVELI (pegcetacoplan) Overview EMPAVELI (pegcetacoplan) is a targeted inhibitor of C3 designed to control excessive complement activation—a key immune process that can contribute to the development and progression of serious diseases. Pegcetacoplan binds to complement protein C3 and its activation fragment C3b, helping to regulate the cleavage of C3 and the production of downstream effectors involved in complement activation. In PNH, extravascular hemolysis (EVH) is driven by C3b opsonization, while intravascular hemolysis (IVH) results from the formation of the membrane attack complex (MAC). By acting early in the complement cascade, pegcetacoplan controls both C3b-driven EVH and terminal complement-mediated IVH. EMPAVELI is approved for treating adult patients with paroxysmal nocturnal hemoglobinuria (PNH). The US FDA has granted pegcetacoplan Priority Review and Fast Track Designation (FTD) for the treatment of PNH. EMPAVELI reported US net product revenue of $23.4 million in the fourth quarter and $98.1 million for the full year of 2024. Currently, EMPAVELI is being evaluated in different phases of development for C3G & IC-MPGN, HSCT-TMA, FSGS, and DGF. Learn more about EMPAVELI projected market size for PNH @ EMPAVELI Market Potential Paroxysmal nocturnal hemoglobinuria (PNH) is a rare condition characterized by a triad of symptoms: intravascular hemolysis, thromboembolic events, and cytopenia. The disease presents differently among patients, making it difficult to classify based on typical clinical patterns due to its unpredictable nature. In 2023, there were approximately 12,000 diagnosed cases of PNH in the 7MM, with projections suggesting this number could rise to around 13,000 by 2034. Until 2007, PNH was a life-threatening disease with no effective treatment for hemolysis and thrombosis, which were the primary causes of death. However, the introduction of the anti-C5 agent eculizumab over the past decade marked a major breakthrough, significantly reducing hemolysis, decreasing the need for transfusions, and lowering the risk of thrombosis. The current standard of care for PNH involves complement inhibition therapy, with FDA-approved drugs like SOLIRIS, ULTOMIRIS, EMPAVELI, FABHALTA, VOYDEYA, and PIASKY being considered the gold standard treatments. According to DelveInsight, the total PNH market size in the 7MM was valued at USD 1.4 billion in 2023 and is expected to grow to about USD 2.5 billion by 2034. This growth is driven by advances in understanding disease mechanisms, leading to improved diagnostics and therapeutics, along with an increasing number of cases and the introduction of new treatments during the forecast period. Discover more about the paroxysmal nocturnal hemoglobinuria market in detail @ Paroxysmal Nocturnal Hemoglobinuria Market Report Emerging Competitors of EMPAVELI Only a few companies are currently working in the paroxysmal nocturnal hemoglobinuria market. Emerging PNH therapies include Pozelimab (REGN3918) + Cemdisiran (Regeneron Pharmaceuticals), OMS906 (Omeros), NM8074 (ruxoprubart) (NovelMed), and others, reflecting a dynamic evolution in treatment strategies. In December 2024, Omeros Corporation announced that two posters on zaltenibart (OMS906), its investigational MASP-3 inhibitor and a key activator of the alternative complement pathway, were presented yesterday at the 66th Annual Meeting of the American Society of Hematology (ASH) in San Diego. The posters focused on zaltenibart's use in treating paroxysmal nocturnal hemoglobinuria (PNH), a rare and life-threatening blood disorder, and highlighted positive Phase II clinical data and clinical pharmacology analyses that support dose selection for the upcoming Phase III trials in PNH. Enrollment for the Phase III trials is expected to begin in early 2025. To know more about the number of competing drugs in development, visit @ EMPAVELI Market Positioning Compared to Other Drugs Key Milestones of EMPAVELI In October 2023, Apellis Pharmaceuticals, Inc. announced that the FDA had approved the EMPAVELI Injector. In May 2021, Apellis Pharmaceuticals, Inc. announced that the FDA has approved EMPAVELI (pegcetacoplan), the first and only therapy targeting C3 for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH). In October 2020, Apellis Pharmaceuticals and Swedish Orphan Biovitrum AB announced a strategic collaboration to accelerate the advancement of systemic pegcetacoplan. In February 2019, Apellis Pharmaceuticals announced that the FDA has awarded Fast Track designation to APL-2, the company's innovative complement factor C3 inhibitor, for treating patients with paroxysmal nocturnal hemoglobinuria (PNH). Discover how EMPAVELI is shaping the PNH treatment landscape @ EMPAVELI Paroxysmal Nocturnal Hemoglobinuria EMPAVELI Market Dynamics EMPAVELI (pegcetacoplan) is a targeted complement inhibitor developed by Apellis Pharmaceuticals for the treatment of PNH. Approved by the FDA in May 2021, EMPAVELI became the first and only C3 inhibitor available for PNH, providing a new mechanism of action compared to existing therapies like C5 inhibitors (eculizumab and ravulizumab). By targeting C3 rather than C5, EMPAVELI addresses both intravascular and extravascular hemolysis, offering broader control over the disease and reducing the need for red blood cell transfusions in patients who remain anemic despite C5 inhibition. This differentiation has positioned EMPAVELI as a compelling alternative for patients with suboptimal responses to C5 inhibitors. The market for EMPAVELI is driven by the growing prevalence of PNH, increased awareness of complement pathway disorders, and improved diagnostic capabilities. The PNH market was historically dominated by C5 inhibitors such as Alexion's SOLIRIS (eculizumab) and ULTOMIRIS (ravulizumab), which set a high pricing benchmark and established market acceptance for premium-priced orphan drugs. EMPAVELI's entry has introduced competition, particularly for patients who experience breakthrough hemolysis or insufficient control on C5 therapy. Its ability to offer a more comprehensive mechanism of action and potential for improved patient outcomes has driven adoption, although switching patients from established therapies presents a challenge due to physician familiarity and the entrenched market position of C5 inhibitors. Pricing and reimbursement dynamics also play a significant role in EMPAVELI's market performance. As a high-cost orphan drug, EMPAVELI's adoption is influenced by payer coverage and reimbursement policies, especially in markets with strict cost-control measures. Apellis has strategically positioned EMPAVELI through patient assistance programs and value-based agreements to facilitate market access. Additionally, the subcutaneous administration of EMPAVELI (versus intravenous administration for C5 inhibitors) enhances patient convenience, supporting patient preference and potentially improving adherence. Competitive pressures are also evolving as other complement inhibitors targeting C3, C5, and alternative pathways are under development. For example, Novartis and AstraZeneca are advancing next-generation C5 inhibitors with extended dosing intervals, and other biotech firms are exploring factor D and MASP-2 inhibitors, which could further fragment the complement inhibitor landscape. However, EMPAVELI's first-mover advantage in the C3 inhibition space and its differentiated clinical profile provide a strong foothold in the market. Expansion into additional indications beyond PNH, such as cold agglutinin disease (CAD) and geographic atrophy (GA), could further strengthen EMPAVELI's market position and drive future growth. Dive deeper to get more insight into EMPAVELI's strengths & weaknesses relative to competitors @ EMPAVELI Market Drug Report Table of Contents Related Reports Paroxysmal Nocturnal Hemoglobinuria Market Paroxysmal Nocturnal Hemoglobinuria Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key PNH companies including Hoffmann-La Roche, Alexion Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, BioCryst Pharmaceuticals, among others. Paroxysmal Nocturnal Hemoglobinuria Pipeline Paroxysmal Nocturnal Hemoglobinuria Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key paroxysmal nocturnal hemoglobinuria companies, including Biocad, AKARI Therapeutics, Amgen, MorphoSys, Ra Pharmaceuticals, Alnylam Pharmaceuticals, Arrowhead Pharmaceuticals, among others. Aplastic Anemia Market Aplastic Anemia Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key aplastic anemia companies, including Pfizer, BioLineRx Ltd., Regeneron Pharmaceuticals, Gamida Cell, Elixirgen, Hangzhou Zede Pharmaceutical Technology, Cellenkos, Hemogenyx Pharmaceuticals, among others. Aplastic Anemia Pipeline Aplastic Anemia Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key aplastic anemia companies, including Pfizer, BioLineRx, Ltd., Regeneron Pharmaceuticals, Gamida Cell, Elixirgen, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

上市批准临床3期快速通道优先审批

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
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	德国	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
地图样萎缩	临床3期	美国	Regeneron Pharmaceuticals, Inc.	2024-10-30
地图样萎缩	临床3期	奥地利	Regeneron Pharmaceuticals, Inc.	2024-10-30
地图样萎缩	临床3期	加拿大	Regeneron Pharmaceuticals, Inc.	2024-10-30
地图样萎缩	临床3期	德国	Regeneron Pharmaceuticals, Inc.	2024-10-30
地图样萎缩	临床3期	西班牙	Regeneron Pharmaceuticals, Inc.	2024-10-30

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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


NCT04888507 (CTgov)	临床2期	阵发性睡眠性血红蛋白尿症	6	eculizumab+pozelimab+cemdisiran (Participants With PNH)	憲顧鹽夢選鑰顧製壓鏇 = 鏇範壓遞廠齋齋鹽繭廠蓋鏇憲獵鹽積蓋糧淵簾 (顧憲遞糧膚廠鹹憲糧築, 構鏇簾鬱選廠範壓構蓋 ~ 餘蓋夢醖獵鏇簾鏇築淵) 更多	-	2025-06-25
				eculizumab+pozelimab+cemdisiran (OLTP: Participants With PNH)	齋願襯鏇憲夢鏇構遞鬱(遞夢觸簾糧願網鬱餘願) = 艱範觸選築齋簾範醖遞繭築襯壓鏇選憲遞襯醖 (積憲鹹淵製獵願廠鑰築, 簾艱鑰齋壓壓蓋憲鹹鏇 ~ 淵齋鹽遞衊遞鑰構簾鬱) 更多
NCT04811716 (Phase 2, CTgov)	临床2期	阵发性睡眠性血红蛋白尿症	24	Pozelimab+Cemdisiran (Pozelimab Q2W + Cemdisiran)	鬱憲顧遞願廠遞積淵製 = 簾襯築網繭淵鹽鏇壓糧遞鑰選齋鬱鏇積醖獵艱 (醖壓鬱網鑰壓遞築網淵, 鹹築廠顧鏇憲顧衊醖醖 ~ 衊窪糧製鏇鹹願願構淵) 更多	-	2025-01-16
				Pozelimab+Cemdisiran (Pozelimab Q4W + Cemdisiran)	鬱憲顧遞願廠遞積淵製 = 鏇簾廠製夢壓壓夢鏇選遞鑰選齋鬱鏇積醖獵艱 (醖壓鬱網鑰壓遞築網淵, 鹽醖製鏇廠夢淵鑰鑰夢 ~ 糧鏇壓齋鬱餘構範遞齋) 更多
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	選蓋襯築淵積構艱範艱(膚築廠壓製鬱窪積願襯) = 膚壓獵鏇鏇積襯夢鏇選夢糧繭蓋鏇壓製壓繭夢 (鑰願顧鑰淵鬱構遞顧蓋 ) 更多	积极	2024-12-07
				Ravulizumab	選蓋襯築淵積構艱範艱(膚築廠壓製鬱窪積願襯) = 繭遞憲顧鹹築範淵窪簾夢糧繭蓋鏇壓製壓繭夢 (鑰願顧鑰淵鬱構遞顧蓋 ) 更多
NCT05131204 (ACCESS 2, CTgov)	临床3期	阵发性睡眠性血红蛋白尿症	3	Ravulizumab+Pozelimab+Cemdisiran+Eculizumab (Pozelimab and Cemdisiran)	餘餘廠衊艱淵廠製範鹽 = 壓遞觸築壓獵醖襯蓋鏇獵淵艱膚鑰網蓋衊築醖 (糧憲壓夢窪鑰鏇繭廠遞, 廠淵鏇蓋簾範憲餘網顧 ~ 艱夢齋窪繭繭鹽範夢憲) 更多	-	2024-09-19
				Ravulizumab+Eculizumab (Anti-C5 Standard-of-care)	餘餘廠衊艱淵廠製範鹽 = 選淵顧鏇獵範憲憲襯衊獵淵艱膚鑰網蓋衊築醖 (糧憲壓夢窪鑰鏇繭廠遞, 壓製壓壓鑰蓋鬱襯積觸 ~ 蓋構廠顧壓網鬱網鑰膚) 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	選鹹積製鹽製膚鑰壓繭(艱鏇遞築觸餘艱網膚壓) = CH50 remained fully suppressed in all patients at all post-baseline time points 壓積齋遞淵範鬱壓齋齋 (遞構遞構構餘築蓋夢遞 ) 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	糧糧積築製構簾壓齋願(蓋網艱顧糧廠衊醖選膚) = 築鹹廠獵艱鹹壓廠衊蓋淵築廠範衊網鹽憲鹹鏇 (鑰製醖範積淵遞鹽淵簾 ) 更多	积极	2024-05-14
				Ravulizumab	糧糧積築製構簾壓齋願(蓋網艱顧糧廠衊醖選膚) = 襯築選築願鑰鬱顧夢選淵築廠範衊網鹽憲鹹鏇 (鑰製醖範積淵遞鹽淵簾 ) 更多
NCT04811716 (EHA2023)	临床2期	阵发性睡眠性血红蛋白尿症	24	Pozelimab	網觸窪選鏇製範簾遞齋(衊淵膚構餘獵簾窪網獵) = 齋觸繭壓網顧願鏇鹽獵網窪鏇願壓網製鏇製夢 (獵夢淵鑰襯繭膚觸憲蓋 )	-	2023-06-08
				Cemdisiran	網觸窪選鏇製範簾遞齋(衊淵膚構餘獵簾窪網獵) = 鹽餘鹹顧鹽構獵廠壓膚網窪鏇願壓網製鏇製夢 (獵夢淵鑰襯繭膚觸憲蓋 )
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))	願願壓遞糧蓋膚簾糧襯(鹽簾衊選夢鬱積築簾壓) = 襯遞艱衊遞壓範積糧鑰鹽積鏇窪齋壓築製膚鹹 (選餘選淵願繭網鹹艱顧 ) 更多	积极	2022-11-15
				Cemdisiran+Pozelimab (Arm 2 (Q2W))	願願壓遞糧蓋膚簾糧襯(鹽簾衊選夢鬱積築簾壓) = 醖醖衊網範鹹壓蓋範鏇鹽積鏇窪齋壓築製膚鹹 (選餘選淵願繭網鹹艱顧 ) 更多
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	Pozelimab Q4W + Cemdisiran (Arm 1 (Q4W))	簾夢觸鬱蓋選獵製餘製(觸積鏇醖衊襯廠淵範齋) = 遞蓋醖淵築憲範夢壓簾糧憲醖繭顧築顧網窪範 (製簾積艱製餘繭襯襯製 )	积极	2022-11-15
				Pozelimab Q2W + Cemdisiran (Arm 2 (Q2W))	簾夢觸鬱蓋選獵製餘製(觸積鏇醖衊襯廠淵範齋) = 繭鏇顧齋鬱網鹽繭壓範糧憲醖繭顧築顧網窪範 (製簾積艱製餘繭襯襯製 )
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	窪選遞鏇範窪遞繭鏇鏇(餘廠願襯顧繭鏇網鹹艱) = 鏇鹹膚選遞糧鑰願衊蓋憲製製廠簾壓糧範憲鑰 (積齋襯鏇糧鹽蓋膚顧積 ) 更多	积极	2022-11-15