Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Sirukumab in Confirmed Severe or Critical COVID-19 Disease

The purpose of this study is to evaluate the clinical response of sirukumab (administered as a single intravenous dose) plus standard of care (SOC) compared to placebo plus SOC in COVID-19.

开始日期2020-04-24

申办/合作机构

Janssen Pharmaceutica NV

NCT02899026

/ Withdrawn临床3期

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Sirukumab in Subjects With Polymyalgia Rheumatica

Sirukumab is a human anti-IL-6 monoclonal antibody that selectively binds to the cytokine with high affinity that may have therapeutic benefit in the treatment of polymyalgia rheumatica (PMR) by interrupting multiple pathogenic pathways. Sirukumab inhibits IL-6-mediated signal transducer and activator of transcription 3 (STAT3) phosphorylation, resulting in the inhibition of the biological effect of IL-6. This study will evaluate the efficacy and safety of sirukumab to characterize the benefit-to-risk profile of sirukumab in the treatment of active PMR. The study will be conducted in 2 parts (Part A and Part B) and consists of the following phases: Screening phase, Part A: 52-week double-blind treatment phase, Part B: 52-week extension phase with no study drug administration and a 16-week follow-up phase if applicable.
Approximately 150 subjects with a diagnosis of PMR and active disease within 6 weeks of baseline will be randomized into Part A, the 52-week double-blind treatment phase, to receive one of two doses of sirukumab or placebo, each in addition to a pre-specified prednisone taper. The efficacy and safety of sirukumab in sustaining remission will be assessed at Week 52. Subjects completing Part A of the study who are in clinical remission will be eligible to enter Part B, the 52-week extension phase, designed to investigate the long-term maintenance of remission and safety following cessation of sirukumab treatment and to assess long-term corticosteroid use. Subjects will need to have follow-up safety evaluations for at least 16 weeks after receiving the last dose of study drug, applicable for those who have withdrawn prematurely from the study or who have completed Part A but are not eligible for Part B.

开始日期2018-03-15

申办/合作机构

GSK Plc

NCT02794519

/ Withdrawn临床2期

205076: A Phase II, Multicenter, Randomized, Double-blind (Sponsor-unblind), Placebo- Controlled, Parallel Group Trial to Evaluate the Efficacy and Safety of Sirukumab in Subjects With Severe, Poorly Controlled Asthma

Sirukumab is a fully human anti interleukin (IL)-6 immunoglobulin G1-kappa monoclonal antibody (MAb) which is in development for the treatment of rheumatoid arthritis (RA). The continuing unmet need in subjects with asthma refractory to corticosteroid therapy and increased understanding of asthma pathogenesis have stimulated the development of targeted biologics based on predictive biomarkers. The majority of approaches to date have targeted T Helper 2 (Th2) cytokines or their downstream effects. Targeting IL-6 in severe asthma represents an unprecedented approach that has potential to address non-Th2 drivers of severe asthma. This multicenter, randomized, double-blind (sponsor-unblind), placebo-controlled, parallel group study will investigate the efficacy of sirukumab compared to placebo in subjects having uncontrolled severe asthma despite use of high dose inhaled corticosteroid (ICS) in combination with long-acting Beta-agonist (LABA). The study will employ a variable treatment period for individual subjects. Dosing will continue every 4 weeks until week 44 (inclusive), or until 24 weeks after the final subject has been randomized, whichever the sooner. Upon receiving the final dose of study medicine or placebo, subjects will enter a 16 week Follow Up period. Overall, the duration of participation for subjects who complete the full 44-week treatment period and Follow Up period may be up to 64 weeks. Approximately 175 subjects will be randomized such that 140 evaluable subjects complete the study.

开始日期2016-09-23

申办/合作机构

GSK Plc

100 项与 Sirukumab 相关的临床结果

登录后查看更多信息

100 项与 Sirukumab 相关的转化医学

登录后查看更多信息

100 项与 Sirukumab 相关的专利（医药）

登录后查看更多信息

项与 Sirukumab 相关的文献（医药）

2024-12-01·JOURNAL OF INFECTION

Corrigendum to “The IL-6 hypothesis in COVID-19: A phase 2, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of free IL-6 sequestration by the monoclonal antibody sirukumab in severe and critical COVID-19” [J Infect 89 (2024) 106241]

作者: Foong, Kap Sum

2024-10-01·JOURNAL OF INFECTION

The IL-6 hypothesis in COVID-19: A phase 2, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of free IL-6 sequestration by the monoclonal antibody sirukumab in severe and critical COVID-19

Article

作者: Buelens, Annemie ; Verbrugge, Inge ; De Meyer, Sandra ; Robinson, Philip ; Spak, Cedric W ; Chien, Jason W. ; Opsomer, Magda ; Slim, Jihad ; Chien, Jason W ; Van Landuyt, Erika ; Van Wesenbeeck, Liesbeth ; Cook, Paul ; Deveikis, Audra ; Clement, Meredith ; Callewaert, Katleen ; Mo, Wai Ling ; Zhuang, Yanli ; Gottlieb, Robert L ; Gottlieb, Robert L. ; Foong, Kap Sum ; Spak, Cedric W.

BACKGROUND:

Upregulation of IL-6 has been associated with worse prognosis in COVID-19 patients. Impact on IL-6 signalling has mostly been limited to clinical outcomes in IL-6 receptor antagonist trials.

METHODS:

We performed a phase 2, randomised, double-blind, placebo-controlled trial (NCT04380961) of US-based hospitalised adults (<85 years) with laboratory-confirmed SARS-CoV-2 infection and severe (low levels of supplemental oxygen) or critical disease (high levels of oxygen supplementation). Patients received sirukumab 5 mg/kg or placebo single dose IV on Day 1 plus standard of care. The primary endpoint was time to sustained clinical improvement up to Day 28 based on an ordinal scale. Secondary endpoints included clinical improvement, all-cause mortality, and safety. Following an interim analysis, the protocol was amended to only recruit patients with critical COVID-19.

FINDINGS:

From May 2020 to March 2021, 209 patients were randomised; 112 had critical disease (72 sirukumab, 40 placebo) at baseline. Median time to sustained clinical improvement in critical patients was 17 and 23 days in the sirukumab and placebo groups (HR, 1∙1; 95% CI, 0∙66-1∙88; p > 0∙05). At Day 28, 59∙4% versus 55∙0% of patients achieved clinical improvement with sirukumab versus placebo and rates of all-cause mortality were 24∙6% versus 30∙0%, respectively. Rates of grade ≥3 adverse events were comparable between the sirukumab and placebo groups (25∙9% vs 32∙9%; all patients).

INTERPRETATION:

In critical COVID-19 patients who received sirukumab, there was no statistically significant difference in time to sustained clinical improvement versus placebo despite objective sequestration of circulating IL-6, questioning IL-6 as a key therapeutic target in COVID-19.

2024-01-01·European journal of medicinal chemistry

Mitochondria-targeted pentacyclic triterpene NIR-AIE derivatives for enhanced chemotherapeutic and chemo-photodynamic combined therapy

Article

作者: Zhang, Xuewei ; Zheng, Jinhong ; Wang, Xiang ; Wang, Jinzhi ; Dong, Mingming ; Zheng, Guoxing ; Yan, Kang ; Lin, Liyin ; Huang, Zhaopeng

Complexes formed by combining pentacyclic triterpenes (PTs) with Aggregation-Induced Emission luminogens (AIEgens), termed pentacyclic triterpene-aggregation induced emission (PT-AIEgen) complexes, merge the chemotherapeutic properties of PTs with the photocytotoxicity of AIEgens. In this study, we synthesized derivatives by connecting three types of triphenylamine (TPA) pyridinium derivatives with three common pentacyclic triterpenes. Altering the connecting group between the electron donor TPA and the electron acceptor pyridinium resulted in increased production of reactive oxygen species (ROS) by PT-AIEgens and a red-shift in their fluorescence emission spectra. Importantly, the fluorescence emission spectra of BA-3, OA-3, and UA-3 extended into the near-infrared (NIR) range, enabling NIR-AIE imaging of the sites where the derivatives aggregated. The incorporation of the pyridinium structure improved the mitochondrial targeting of PT-AIEgens, enhancing mitochondrial pathway-mediated cell apoptosis and improving the efficiency of chemotherapy (CT) and chemo-photodynamic combined therapy (CPCT) both in vivo and in vitro. Cellular fluorescence imaging demonstrated rapid cellular uptake and mitochondrial accumulation of BA-1 (-2, -3). Cell viability experiments revealed that BA-1 (-2), OA-1 (-2), and UA-1 (-2) exhibited superior CT cytotoxicity compared to their parent drugs, with BA-1 showing the most potent inhibitory effect on HeLa cells (IC₅₀ = 1.19 μM). Furthermore, HeLa cells treated with BA-1 (1 μM), BA-2 (1.25 μM), and BA-3 (1 μM) exhibited survival rates of 2.99 % ± 0.05 % μM, 5.92 % ± 2.04 % μM, and 2.53 % ± 0.73 % μM, respectively, under white light irradiation. Mechanistic experiments revealed that derivatives induced cell apoptosis via the mitochondrial apoptosis pathway during both CT and CPCT. Remarkably, BA-1 and BA-3 in CPCT inhibited cancer cell proliferation in an in vivo melanoma mouse xenograft model. These results collectively encourage further research of PT-AIEgens as potential anticancer agents.

项与 Sirukumab 相关的新闻（医药）

2025-12-10

·丁香园精神时间

破局「心灵感冒」：当抑郁症遇见炎症假说

长久以来，我们习惯将抑郁症视为一种纯粹的「心灵感冒」，归因于大脑化学物质失衡，特别是血清素、去甲肾上腺素等神经递质减少。经典的抗抑郁药也大多基于这一「单胺假说」。然而，一个无法回避的临床现实是：近三分之一的患者对所有现有药物都反应不佳，这被称为「难治性抑郁症」。科学家们开始思考，我们是否遗漏了抑郁症拼图中至关重要的一块？近年来，一个颠覆性的理论 —— 抑郁症炎症假说 —— 正从边缘走向中央，为我们打开了理解与治疗抑郁症的全新视角。一、意想不到的关联：从身体发炎到心灵「发炎」你是否曾注意到，在得了流感或重感冒时，会感到情绪低落、疲惫不堪、对万事提不起兴趣？这并非偶然。我们免疫系统在对抗病原体时，会释放一系列名为细胞因子的炎症信号。这些分子原本是用来协调免疫细胞作战的，但它们却有能力「远程操控」我们的大脑。发炎，是身体在「喊救命」；而抑郁，有时可能就是大脑对这种「求救信号」的回应。大量研究证实：抑郁症患者血液中的炎症标志物（如 C 反应蛋白、IL-6、TNF-α）水平显著高于健康人群；患有慢性炎症性疾病（如类风湿关节炎、银屑病）的人，其抑郁症的发病率远高于普通人群；接受干扰素-α（一种强效促炎细胞因子）治疗的肝炎或癌症患者，会诱发严重抑郁症状。这些线索强烈地提示，全身性的炎症反应，可能是驱动或加重抑郁症的一个重要病理生理过程。二、炎症如何「劫持」大脑？炎症并非仅仅让我们「感觉」不舒服，它正在我们的大脑内部发动一场精密的「化学攻击」： 1. 改变神经递质代谢：炎症细胞因子会劫持大脑中色氨酸代谢途径。色氨酸是合成血清素的前体，但炎症会将其引向另一条通路，产生神经毒性物质，从而减少血清素的合成 —— 这完美地解释了传统「单胺假说」观察到现象，并找到其上游原因。 2. 影响神经可塑性：大脑并非一成不变，它需要不断生长和修剪连接来学习和适应，这种能力称为「神经可塑性」。炎症因子会显著抑制脑源性神经营养因子（BDNF）的产生。BDNF 好比是神经元的「肥料」，它的减少会导致海马体（负责记忆和情绪调节）神经元萎缩，连接断裂，这正是抑郁症患者脑影像学中常见改变。 3. 扰乱「奖赏回路」：大脑奖赏系统（涉及多巴胺）让我们感到愉悦和动力。炎症会直接抑制该系统的功能，导致「快感缺失」—— 对曾经热爱的事物失去兴趣，这是抑郁症的核心症状之一。 4. 激活应激反应：炎症与身体应激系统（下丘脑-垂体-肾上腺轴，HPA 轴）形成恶性循环，导致皮质醇（压力激素）水平紊乱，进一步加剧情绪问题。三、从理论到实践：靶向炎症的抑郁症新疗法基于上述发现，科学家们正在积极测试通过抗炎来治疗抑郁症的新策略。这并非鼓励大家自行服用布洛芬，而是开发精准靶向药物。 1. 「老药新用」的探索：一些研究将传统的抗炎药，如塞来昔布（一种 COX-2 抑制剂），与抗抑郁药联用，在难治性抑郁症患者中显示出比单用抗抑郁药更好的疗效。它像是一个「辅助」，帮助清除大脑中的炎症干扰。 2. 生物制剂精准打击：这是最前沿的方向。针对特定炎症因子（如 TNF-α、IL-6）的单克隆抗体已经应用于治疗自身免疫病。初步临床试验显示，对于血液中炎症标志物水平高的抑郁症患者，使用英夫利西单抗（抗 TNF-α 抗体）或 Sirukumab（抗 IL-6 抗体）能显著改善其抑郁症状。这标志着「精准精神病学」雏形 —— 未来我们可能先检测患者的炎症水平，再为其选择最合适药物。 3. 氯胺酮的启示：被誉为「奇迹药物」的氯胺酮，其快速抗抑郁的机制之一，也被认为与强大的抗炎作用有关。它能迅速降低大脑中的炎症信号，并快速促进 BDNF 的释放，从而修复受损的神经连接。四、思考与展望：这对我们意味着什么？抑郁症的炎症假说，不仅仅关乎新药研发，它更赋予我们一种全新健康视角： 1. 身心一体不再是空话：它从生物学层面证实，身体的健康（免疫系统）与心理的健康（情绪）密不可分。管理好慢性感染、牙周病、肥胖、肠道菌群紊乱等潜在炎症源，可能就是对心灵最好的呵护。 2. 生活方式「抗炎」力量：均衡饮食（如地中海饮食富含 Omega-3）、规律运动、充足睡眠和压力管理，都被证实具有明确的抗炎效果。这些传统建议如今有了更坚实的科学背书。 3. 去污名化的新角度：将抑郁症部分归因于身体的生物学过程（炎症），有助于减少患者「意志薄弱」的自我指责和外界偏见。它是一种真实的、有生理基础的疾病。当然，挑战依然存在。并非所有抑郁症患者都由炎症驱动，如何精准识别适合抗炎治疗的「炎症亚型」是下一步研究的关键。未来，当我们再谈起抑郁症时，画面将不再仅仅是阴郁的情绪和失衡的化学物质，还可能包括一场发生在大脑微环境中、静默却激烈的「免疫风暴」。而平息这场风暴，将成为我们战胜抑郁症的全新利器。题图 | 站酷海洛排版 | 江十一欢迎投稿 | einsmeer@foxmail.com 参考文献 1. Troubat, R., et al. (2021). The neuroinflammatory hypothesis of depression: evidence from human and animal studies. Nature Reviews Immunology, 21(1), 1-14. 2. Köhler-Forsberg, O., et al. (2023). Efficacy of anti-inflammatory treatment on major depressive disorder or depressive symptoms: a meta-analysis of randomized clinical trials. JAMA Psychiatry, 80(5), 449-457. 3. Miller, A. H., & Raison, C. L. (2022). The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nature Reviews Immunology, 22(5), 267-282. 4. Haroon, E., & Miller, A. H. (2023). Inflammation effects on brain glutamate in depression: mechanistic considerations and treatment implications. Current Topics in Behavioral Neurosciences, 61, 265-282.

2023-12-01

·SYNAPSE

Deciphering IL-6 Inhibitors: Your Guide to Rapidly Accessing the Newest Advances

IL-6, or Interleukin-6, is a cytokine that plays a crucial role in the human body's immune response and inflammation regulation. It is produced by various cells, including immune cells, and acts as a signaling molecule to stimulate the immune system during infection or injury. IL-6 also plays a role in the development and differentiation of immune cells, such as B cells and T cells. However, excessive or prolonged IL-6 production can lead to chronic inflammation and contribute to the pathogenesis of various diseases, including autoimmune disorders and certain cancers. Therefore, understanding and regulating IL-6 levels is of great importance in the pharmaceutical industry for the development of targeted therapies. IL-6 Inhibitors is relevant to many inflammatory diseases and cancers. The first approved medication in this class was tocilizumab (Actemra), an antibody directed against the IL-6 receptor. This was followed by siltuximab (Sylvant), which is directed against IL-6 itself. Sarilumab was approved by the US FDA in 2017 for rheumatoid arthritis. Several other agents are in clinical trials, including olokizumab (CDP6038), elsilimomab, clazakizumab (BMS-945429, ALD518), sirukumab (CNTO 136), levilimab (BCD-089), and CPSI-2364. Looking ahead, IL-6 inhibitors are expected to continue to play a significant role in the treatment of various diseases. They have shown promising results in treating serious COVID-19 cases2 and are also used widely for the treatment of rheumatoid arthritis2. The IL-6 inhibitors market is projected to grow at a CAGR of 10.9%, increasing from US$ 33.3 Billion in 2023 to US$ 93.3 Billion by 20333. However, the emergence of resistance and the lack of an effective reversal drug when bleeding occurs are challenges that need to be addressed. Ongoing research and development efforts are focused on addressing these issues and expanding the clinical applications of IL-6 inhibitors. Based on the analysis of the data, the current competitive landscape for target IL-6 is characterized by the presence of multiple companies with varying stages of development and a wide range of indications. Bristol Myers Squibb Co. stands out as the company with the highest stage of development, with multiple approved drugs and ongoing clinical trials. Small molecule drugs, molecular glues, and monoclonal antibodies are the most rapidly progressing drug types under the target IL-6. The United States, European Union, and China are the leading countries/locations in terms of development, with China showing significant progress. Overall, the target IL-6 presents a competitive landscape with diverse players and promising future development potential. How do they work?IL-6 inhibitors are a type of medication that target and inhibit the activity of interleukin-6 (IL-6), a cytokine involved in the immune response and inflammation. From a biomedical perspective, IL-6 inhibitors are used in the treatment of various inflammatory conditions such as rheumatoid arthritis, systemic juvenile idiopathic arthritis, and Castleman's disease. These inhibitors work by blocking the binding of IL-6 to its receptor, thereby reducing the inflammatory response mediated by IL-6. By inhibiting IL-6, these medications help alleviate symptoms and reduce disease progression in patients with IL-6-mediated inflammatory disorders List of IL-6 InhibitorsThe currently marketed IL-6 inhibitors include: SiltuximabPomalidomidePirfenidoneLenalidomideOlokizumabSirukumabSodium PyruvateClazakizumabRO-7200220ZiltivekimabFor more information, please click on the image below. What are IL-6 inhibitors used for?IL-6 inhibitors are used in the treatment of various inflammatory conditions such as rheumatoid arthritis, systemic juvenile idiopathic arthritis, and Castleman's disease. For more information, please click on the image below to log in and search. How to obtain the latest development progress of IL-6 inhibitors?In the Synapse database, you can keep abreast of the latest research and development advances of IL-6 inhibitors anywhere and anytime, daily or weekly, through the "Set Alert" function. Click on the image below to embark on a brand new journey of drug discovery!

2021-02-04

·佰傲谷BioValley

靶向IL-6疗法的十年

细胞因子抑制剂已经改变了许多慢性炎症疾病的结果。自批准抗IL-6受体(anti-IL-6R)疗法以来，已经过去了十年。目前在世界范围内广泛应用于各种风湿性疾病，如类风湿关节炎(RA)、幼年特发性关节炎(JIA)、成人起病性Still’s病(AOSD)、巨细胞动脉炎(GCA)和高山动脉炎，以及其他疾病，如Castleman病和细胞因子释放综合征(CRS)。此外，还确定了可能扩展到其他几种适应症的途径，如葡萄膜炎、视神经脊髓炎以及最近的COVID-19肺炎。从信号传递到药物发现自40多年前被发现以来，IL-6通路已成为参与健康免疫调节和多种疾病失调的关键通路。 1973年，大阪大学由Kishimoto tadmitsu领导的研究人员首次报道了T细胞分泌的一种可溶性因子对B细胞产生抗体很重要，随后，这种可溶性因子被克隆为IL-6，它在多种自身免疫性疾病中发挥着不同的作用。与此同时，中外制药的研究人员正在探索治疗自身免疫性疾病药物开发的新途径。 20世纪80年代末，两组开始合作，进一步加深对IL-6在各种自身免疫性疾病中的生物学作用的认识，并开发IL-6抑制剂作为治疗选择。为了增加他们合作的可能，两个研究小组甚至搬到了大阪大学毗邻的实验室。该大学的研究人员负责识别IL-6信号机制和IL-6的生物学效应，而该公司则专注于开发IL-6抑制剂，作为自身免疫性疾病潜在的新疗法。发现IL-6和IL-6靶向治疗的时间表当研究小组发现IL-6信号转导是通过IL-6、IL-6R和糖蛋白130的六聚体高亲和力复合物发生时，寻找小分子抑制剂的传统方法被证明具有挑战性。此外，可溶性IL-6R (sIL-6R)和膜结合的IL-6R (mIL-6R)都可以成为六聚体复合物的一部分；因此，认为IL-6 - IL - 6r - gp130的结合区域过于复杂和广泛，不足以作为小分子化合物抑制IL-6信号通路。后随着生物技术的同步发展，两组决定开发一种靶向IL-6R的人源化单克隆抗体。所得到的IL-6R人源化抗体tocilizumab与IL-6R和sIL-6R结合，并通过阻止IL-6与IL-6R结合来抑制IL-6信号转导。这种抗体对IL-6R的治疗益处加速了几种IL-6抗体(sirukumab, olokizumab 和 clazakizumab)的发展。 IL-6在疾病中的细胞信号通路和生理作用初始治疗应用众所周知，IL-6具有多种生理作用，在将IL-6作为治疗靶点时，其在各种自身免疫性疾病中的稳态作用与致病作用之间存在着广泛的争论。然而，利用基于细胞的分析、动物模型和体外血清和组织分析，科学家发现了几种可能受益于IL-6抑制的候选疾病。 IL-6抑制对疾病影响的证据除上述适应症，IL-6通路抑制在不同治疗领域的治疗潜力正在进行临床研究。这些疾病包括葡萄膜炎、甲状腺眼病、视神经脊髓炎、移植物抗宿主病、侵蚀性手部骨关节炎、各种肿瘤指征、抑郁症、精神分裂症、心肌梗死、家族性地中海热和COVID-19肺炎(由新型冠状病毒SARS-CoV-2引起)等。其中，一项II期临床试验正在意大利进行，FDA于2020年3月批准的一项III期临床试验，以评估tocilizumab治疗重症COVID-19肺炎的效果。希望这些研究中的一些发现将在未来扩大IL-6通路抑制在其他疾病中的应用和医学价值。安全性方面，IL-6通路抑制剂治疗与转氨酶血清浓度升高有关。在临床试验中，这些升高似乎不会导致永久性或临床明显的肝损伤。当潜在的肝毒性药物(如甲氨蝶呤)与IL-6途径抑制剂联合使用时，转氨酶升高的频率和幅度增加。此外，胰腺炎是使用tocilizumab和sarilumab的不良反应之一。胃肠道穿孔也与这些药物的使用有关。长期暴露人群胃肠道穿孔的总发生率与类风湿关节炎一致。生物疗法的另一个安全问题是抗药物抗体的开发，其可导致功效丧失和/或免疫介导的不良反应。一项评估tocilizumab在类风湿关节炎患者中的免疫原性的研究发现，无论tocilizumab作为单药治疗或与csDMARDs联合使用，tocilizumab抗体的发生率都很低；此外，抗tocilizumab 的抗体大多是暂时性的，其发展与药代动力学、安全性事件或疗效丧失无关。对于sirukumab，FDA拒绝批准该药物用于RA，原因是考虑到在III期研究中sirukumab和安慰剂组的全因死亡率不平衡，尽管尚不清楚这种不平衡是真正的安全信号还是研究设计的结果。需要更多的研究来进一步确定sirukumab的安全性。以IL-6 信号通路为靶点的药物研究进展目前，以 IL-6 信号通路为靶点的生物技术药物已成为研发热点。国际市场方面，FDA已经批准了三款，FDA批准上市的分别为Tocilizumab（托珠单抗，商品名：Actemra /RoActemra）、Siltuximab（商品名：Sylvant）、Sarilumab（商品名：Kevzara）。其中，托珠单抗由日本公司Chugai（日本中外制药）与罗氏共同开发，是一款靶向IL-6R的人源化单抗，2010年在美国上市，是全球首款上市的IL-6信号通路单抗。用于治疗中度到重度，且之前接受过一种或多种效果不佳抗风湿性治疗的活动性类风湿性关节炎（以下简称RA）。目前的适应症，除了RA，还包括巨细胞动脉炎（Giant Cell Arteritis）、SJIA（全身性幼年特发性关节炎）、PJIA（幼年特发性关节炎）、以及Cart疗法引发的CRS（细胞因子释放综合征）。不过特别要注意一点，2019年5月，加拿大卫生部发布信息，报道了患者在使用托珠单抗中的严重药物性肝损伤，提示了其的肝毒性风险。罕见病药物 Siltuximab 靶向IL-6 ，由强生公司研发，是一款嵌合型抗体。2014年由FDA批准上市，用于治疗多中心型巨大淋巴结增生症（Mlticentric Castleman’s Disease, 以下简称MCD），且HIV和HHV-8都是阴性。 MCD是一种非常罕见的血液疾病，根据预测，美国和欧洲大约有3600名患者。Sylvant是FDA批准的首个MCD领域的药物。 Sarilumab 靶向IL-6Rα，是一款全人源单抗，由再生元和赛诺菲研发，是RA领域第二款上市的的IL-6信号通路为靶点的单抗。2017年5月在美国获批用于治疗中度到重度的活性RA（之前接受过一次或者多次的抗风湿疗法）。此外，Sarilumab有着不错的前景。除全人源单抗更好的安全性外，自体免疫领域有巨大市场，以及部分患者对于TNF单抗的不耐受和效果不佳，Global Data预测其在2026年能达到7亿美金的销量。国内方面，上市的仅有托珠单抗一款。此外，据2019 年1月24日 CDE 网站数据显示，药品审评中心（CDE）受理的相关品种共有11个，其中7个处于临床研究阶段。结语在将IL-6的生物学转化为自身免疫性疾病患者的治疗方面已经取得了重大进展。IL-6途径抑制剂安全性数据的积累为临床医生提供了评估使用这些药物风险的必要知识。IL-6通路抑制剂已显示对RA、JIA、AOSD、GCA、Castleman病和CRS患者有益，并可能对其他自身免疫性疾病甚至更严重的患者有益。然而，预测患者临床成功的临床前研究的局限性是一个主要障碍，需要进行早期的人体概念验证研究。此外，与IL-6生物学有关的几个问题仍未得到解答。例如，为什么会发生IL-6过量产生?为什么IL-6信号抑制对一些与IL-6过量产生相关的疾病(如RA)的患者有临床意义的益处，但不是所有疾病(如RA)的患者有意义? 回答这些问题将有助于我们进一步了解各种自身免疫性疾病是如何在IL-6通路生物学背景下调控的，并有助于为个别患者或患者亚群开发额外的、个性化的治疗方案。由此看来，探索IL-6通路抑制的治疗潜力之旅还远未结束。参考资料： 1. Choy EH, De Benedetti F, Takeuchi T, Hashizume M, John MR, Kishimoto T. Translating IL-6 biology into effective treatments. Nat Rev Rheumatol. 2020 Jun;16(6):335-345. 3. Hashizume M, Tan SL, Takano J, et al, Nishida KInt Rev Immunol. 2015 May; 34(3):265-79. 4. 贾春翠,饶春明.以白细胞介素-6信号通路为靶点的生物技术药物研究进展[J].中国生物制品学杂志,2019,32(9):1048-1053. 版权声明：本文转自佰傲谷BioValley，如不希望被转载的媒体或个人可与我们联系，我们将立即删除【关于药融圈】药融圈围绕我国生物医药产业链，针对生物医药大数据、技术和资本投资、药融园(产业园)等开展系列系统性工作，促进我国生物医药产业健康发展，完善产业链，共同面对全球合作和竞争。点分享点点赞点在看

抗体免疫疗法合作小分子药物基因疗法

100 项与 Sirukumab 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D10080	Sirukumab	L04AC15	DB11803

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
风湿性多肌痛	临床3期	-	GSK Plc	2018-03-15
巨细胞动脉炎	临床3期	美国	GSK Plc	2015-10-16
巨细胞动脉炎	临床3期	澳大利亚	GSK Plc	2015-10-16
巨细胞动脉炎	临床3期	比利时	GSK Plc	2015-10-16
巨细胞动脉炎	临床3期	保加利亚	GSK Plc	2015-10-16
巨细胞动脉炎	临床3期	法国	GSK Plc	2015-10-16
巨细胞动脉炎	临床3期	德国	GSK Plc	2015-10-16
巨细胞动脉炎	临床3期	匈牙利	GSK Plc	2015-10-16
巨细胞动脉炎	临床3期	意大利	GSK Plc	2015-10-16
巨细胞动脉炎	临床3期	荷兰	GSK Plc	2015-10-16

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04380961 (CTgov)	临床2期	新型冠状病毒感染	212	Sirukumab (Sirukumab + SOC)	繭顧構餘積網鑰艱繭鏇(繭醖構願簾簾顧鹽範繭) = 製齋鹹選餘鑰鑰選齋壓膚窪顧醖築鹹鑰構夢鏇 (鹹廠蓋簾糧憲範壓壓窪, 鏇繭艱廠糧壓觸齋糧鏇 ~ 觸鹽鹽獵糧網襯鹹餘廠) 更多	-	2022-06-21
				Placebo (Placebo + SOC)	繭顧構餘積網鑰艱繭鏇(繭醖構願簾簾顧鹽範繭) = 膚壓窪鹽網鑰願糧網範膚窪顧醖築鹹鑰構夢鏇 (鹹廠蓋簾糧憲範壓壓窪, 觸齋淵範醖範製齋窪鏇 ~ 選選餘艱夢遞廠壓範鹹) 更多
NCT02531633 (Pubmed \| Rheumatol Ther) 人工标引	临床3期	巨细胞动脉炎	161	Sirukumab	選觸範築蓋壓醖願鹽窪(網襯範鹽範繭膚壓醖鏇) = 鹽餘簾鏇蓋膚繭鑰夢蓋願鏇窪選艱鹽積範醖鏇 (糧鑰鹽淵鹽獵艱鑰鹽鏇 )	积极	2020-12-01
				Placebo	選觸範築蓋壓醖願鹽窪(網襯範鹽範繭膚壓醖鏇) = 鹽構膚糧遞襯築艱蓋鑰願鏇窪選艱鹽積範醖鏇 (糧鑰鹽淵鹽獵艱鑰鹽鏇 )
NCT02473289 (CTgov)	临床2期	重度抑郁症	193	Placebo	繭餘獵艱積壓齋繭衊願(窪夢衊鏇夢鹹壓簾鬱鏇) = 構範繭醖窪網糧窪餘壓簾鬱糧範壓醖觸襯憲淵 (廠鏇觸選襯壓範簾遞鏇, 1.43) 更多	-	2019-06-11
NCT01856309 (SIRROUND-LTE, CTgov)	临床3期	类风湿关节炎	1,820	Placebo (Placebo to 50 mg q4w Due to EE/LE/CO)	壓壓襯繭壓糧壓鹹窪窪 = 淵膚壓願蓋衊築夢積夢淵製選壓衊製構鬱簾醖 (範廠築蓋齋糧窪齋築獵, 膚網窪選醖製餘製餘製 ~ 淵廠繭鹽壓鹹壓觸簾簾) 更多	-	2019-05-06
				Placebo (Placebo to 100 mg q2w Due to EE/LE/CO)	壓壓襯繭壓糧壓鹹窪窪 = 襯艱艱繭網廠壓繭壓獵淵製選壓衊製構鬱簾醖 (範廠築蓋齋糧窪齋築獵, 憲觸鏇築鹽築衊廠壓壓 ~ 襯鑰願築鏇鑰餘糧鏇選) 更多
NCT02019472 (SIRROUND-H, Pubmed \| Ann Rheum Dis)	临床3期	类风湿关节炎	-	Sirukumab 100mg every 2 weeks	艱鏇膚淵壓構獵齋鏇糧(艱夢夢蓋構鏇觸膚構齋) = 糧繭醖積鬱範顧選廠憲淵窪蓋蓋憲觸齋範廠淵 (選積繭鹹顧衊遞憲觸觸 )	积极	2018-05-01
				Sirukumab 50mg every 4 weeks	艱鏇膚淵壓構獵齋鏇糧(艱夢夢蓋構鏇觸膚構齋) = 網艱鏇鹹糧觸觸憲襯簾淵窪蓋蓋憲觸齋範廠淵 (選積繭鹹顧衊遞憲觸觸 )
NCT01689532 (Pubmed \| J Rheumatol \| Arthritis Res Ther) 人工标引	临床3期	类风湿关节炎	122	Sirukumab (50 mg once every 4 weeks)	範遞廠憲鏇簾襯壓鹽糧(獵觸範選鹽構醖壓顧醖) = 顧鬱選醖憲願鹹鑰壓觸獵鏇顧鬱築鏇觸構積鏇 (鬱範築構鏇醖窪鏇顧願 )	积极	2018-03-07
				Sirukumab (100 mg once every 2 weeks)	範遞廠憲鏇簾襯壓鹽糧(獵觸範選鹽構醖壓顧醖) = 築衊醖鏇遞鹽構餘構網獵鏇顧鬱築鏇觸構積鏇 (鬱範築構鏇醖窪鏇顧願 )
NCT01604343 (SIRROUND-D, CTgov)	临床3期	类风湿关节炎	1,670	Sirukumab	餘鏇衊衊鏇製願淵觸鬱 = 淵艱糧築壓鹹鏇鹽鑰簾衊襯鏇糧壓獵蓋艱積簾 (獵繭醖窪鑰觸觸繭積憲, 願醖顧網構製範艱積廠 ~ 築憲憲觸膚製廠夢遞窪) 更多	-	2018-01-11
NCT01604343 (SIRROUND-D, Pubmed)	临床3期	类风湿关节炎	1,670	Sirukumab 100mg every 2 weeks	簾鏇窪鹽觸鏇網憲獵窪(範願鑰鬱淵齋網簾製構) = 齋鏇壓積醖繭範蓋衊鹽衊齋憲顧範壓夢膚鑰網 (範獵襯襯糧積膚襯夢窪 )	积极	2017-12-01
				Sirukumab 50mg every 4 weeks	簾鏇窪鹽觸鏇網憲獵窪(範願鑰鬱淵齋網簾製構) = 鹽廠製積襯鹽積衊襯蓋衊齋憲顧範壓夢膚鑰網 (範獵襯襯糧積膚襯夢窪 )
NCT02019472 (SIRROUND-H, CTgov)	临床3期	类风湿关节炎	559	Adalimumab (Adalimumab 40 mg)	顧獵顧構鹹衊簾製鏇鹹(餘鑰願憲築觸選顧鹹遞) = 範獵顧憲壓鏇製廠窪餘糧衊淵簾鑰範廠蓋醖窪 (鹽襯衊願窪襯願顧願鹹, 0.851) 更多	-	2017-09-14
				Sirukumab (Sirukumab 50 mg)	顧獵顧構鹹衊簾製鏇鹹(餘鑰願憲築觸選顧鹹遞) = 範壓觸鬱衊鹽壓築鏇鑰糧衊淵簾鑰範廠蓋醖窪 (鹽襯衊願窪襯願顧願鹹, 0.881) 更多
SIRROUND (EULAR2017)	临床3期	类风湿关节炎	2,926	SIR 50mg q4w	築鏇築蓋繭餘餘鑰廠廠(餘獵製鏇夢願築積壓範) = 壓觸糧憲壓繭簾襯觸顧鏇壓襯壓醖簾鹽鏇蓋鹽 (顧選鏇淵齋齋壓遞艱鹽 ) 更多	-	2017-06-14
				SIR 100mg q2w	築鏇築蓋繭餘餘鑰廠廠(餘獵製鏇夢願築積壓範) = 齋築鹽艱廠窪鬱鹹淵遞鏇壓襯壓醖簾鹽鏇蓋鹽 (顧選鏇淵齋齋壓遞艱鹽 ) 更多