更新于：2024-11-01

IL-17A

更新于：2024-11-01

基本信息

别名

CTLA-8、CTLA8、Cytotoxic T-lymphocyte-associated antigen 8

+ [7]

简介

Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:24120361). Signals via IL17RA-IL17RC heterodimeric receptor complex, triggering homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter. This leads to downstream TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, with potential strong immune inflammation (PubMed:19825828, PubMed:21350122, PubMed:17911633, PubMed:18684971, PubMed:8676080, PubMed:24120361). Plays an important role in connecting T cell-mediated adaptive immunity and acute inflammatory response to destroy extracellular bacteria and fungi. As a signature effector cytokine of T-helper 17 cells (Th17), primarily induces neutrophil activation and recruitment at infection and inflammatory sites (By similarity). In airway epithelium, mediates neutrophil chemotaxis via induction of CXCL1 and CXCL5 chemokines (By similarity). In secondary lymphoid organs, contributes to germinal center formation by regulating the chemotactic response of B cells to CXCL12 and CXCL13, enhancing retention of B cells within the germinal centers, B cell somatic hypermutation rate and selection toward plasma cells (By similarity). Effector cytokine of a subset of gamma-delta T cells that functions as part of an inflammatory circuit downstream IL1B, TLR2 and IL23A-IL12B to promote neutrophil recruitment for efficient bacterial clearance (By similarity). Effector cytokine of innate immune cells including invariant natural killer cell (iNKT) and group 3 innate lymphoid cells that mediate initial neutrophilic inflammation (By similarity). Involved in the maintenance of the integrity of epithelial barriers during homeostasis and pathogen infection (PubMed:21350122). Upon acute injury, has a direct role in epithelial barrier formation by regulating OCLN localization and tight junction biogenesis (By similarity). As part of the mucosal immune response induced by commensal bacteria, enhances host's ability to resist pathogenic bacterial and fungal infections by promoting neutrophil recruitment and antimicrobial peptides release (By similarity). In synergy with IL17F, mediates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry of microbes through the epithelial barriers (By similarity). Involved in antiviral host defense through various mechanisms (By similarity). Enhances immunity against West Nile virus by promoting T cell cytotoxicity (By similarity). May play a beneficial role in influenza A virus (H5N1) infection by enhancing B cell recruitment and immune response in the lung (By similarity). Contributes to influenza A virus (H1N1) clearance by driving the differentiation of B-1a B cells, providing for production of virus-specific IgM antibodies at first line of host defense (By similarity).

关联

项与 IL-17A 相关的药物

Vunakizumab

夫那奇珠单抗

靶点

IL-17A

作用机制

IL-17A抑制剂

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段批准上市

首次获批国家/地区

中国

首次获批日期2024-08-20

Xeligekimab

赛立奇单抗

靶点

IL-17A

作用机制

IL-17A抑制剂

在研机构

重庆智翔金泰生物制药股份有限公司

原研机构

智翔（上海）医药科技有限公司

在研适应症

斑块状银屑病 [+2]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

中国

首次获批日期2024-08-20

Bimekizumab

比奇珠单抗

靶点

IL-17A x IL-17F

作用机制

IL-17A抑制剂 [+1]

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段批准上市

首次获批国家/地区

欧盟 [+3]

首次获批日期2021-08-20

668

项与 IL-17A 相关的临床试验

NCT06431750 / Not yet recruitingN/A

Prospective Observational Study to Evaluate Secukinumab Treatment Effectiveness in Pediatric Patients With Active Juvenile Enthesitis-related or Psoriatic Arthritis (Toddler)

This is a multicenter, non-interventional, cohort study in pediatric patients with active juvenile enthesitis-related or psoriatic arthritis

开始日期2025-04-30

申办/合作机构

Novartis Pharmaceuticals Corp.

NCT06630559 / Not yet recruiting临床3期

A Randomized, Active-Controlled, Double-Blind, Phase 3 Study to Compare Efficacy and Safety of CT-P55 with Cosentyx in Patients with Moderate to Severe Plaque Psoriasis

The goal of this Phase 3 clinical trial is to compare efficacy and safety of CT-P55 with Cosentyx in patients with moderate to severe plaque psoriasis

开始日期2025-04-01

申办/合作机构

Celltrion, Inc.

NCT05309616 / Not yet recruiting临床2期IIT

Effects of IL-17A Inhibition on Idiopathic Subglottic Stenosis

The purpose of this phase 2 study is to examine if inhibiting IL-17A activation using the biologic drug Taltz, in idiopathic subglottic stenosis patients will decrease scar fibroblast proliferation therefore reducing or eliminating the need for invasive or repeat surgeries.

开始日期2024-11-15

申办/合作机构

Yale University

100 项与 IL-17A 相关的临床结果

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100 项与 IL-17A 相关的转化医学

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0 项与 IL-17A 相关的专利（医药）

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11,945

项与 IL-17A 相关的文献（医药）

2025-02-01·Parasitology International

Transcriptomic analysis of immune-related genes in Pacific white snook (Centropomus viridis) gills infected with the monogenean parasite Rhabdosynochus viridisi

Article

作者: Medina-Guerrero, Rosa María ; Hernández-Cornejo, Rubí ; Martínez-Brown, Juan Manuel ; Morales-Serna, Francisco Neptalí ; García-Gasca, Alejandra ; Mirabent-Casals, Marian ; Caña-Bozada, Víctor Hugo

The parasite Rhabdosynochus viridisi (Platyhelminthes: Monogenea) infects the Pacific white snook Centropomus viridis gills and can cause adverse effects in the aquaculture industry. The immune responses of Pacific white snook to monogenean infections are poorly understood. Thus, this study aimed to identify differentially expressed genes (DEGs) in the gills of Pacific white snook juveniles experimentally infected with R. viridisi, emphasizing immune-related genes and pathways activated or suppressed during the infection. RNA sequencing was performed on the gills of uninfected (control) and infected fish. The algorithm Seq2Fun was selected without a reference transcriptome to map the reads to transcripts of fishes available from a database for gene orthologs (EcoOmics) and obtain the counting table. The ExpressAnalyst software was used for differential expression and functional analyses. A total of 20,106 transcripts were found, and 1430 (7 %) were differentially expressed genes (DEGs) between infected and control groups. We identified 860 (60 %) downregulated and 570 (40 %) upregulated genes. Thirteen canonical pathways after the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were overrepresented, and most of the DEGs were downregulated, suggesting the inactivation of these pathways. The functions of most of the DEGs with higher fold change found in this study are poorly understood in fish. Even though the well-known pro-inflammatory cytokines remained unchanged in infected gills of C. viridis, and transforming growth factor β (tgfβ) was downregulated, interleukin-17 ligands il17d and il17a/f1, as well as C-X-C motif chemokine receptor 2 (cxcr2) genes were upregulated, indicating that the infection with R. viridisi promotes Th17-like immunity. Overexpression of plasma B cell activity markers such as immunoglobulin light chain-like genes and the v-set pre-B cell surrogate light chain 3 (vpreb3) was also detected in this study. The possible implications of DEGs related to calcium imbalance, hypoxia adaptation, hemostasis, and immunity are discussed. These results will support future studies to improve the prevention and treatment of monogenean infections in finfish aquaculture.

2025-01-01·Brain, Behavior, and Immunity

Stress-induced VIPergic activation mediates microbiota/Th17cell-dependent depressive-like behaviors

Article

作者: Moraskie Alvarez-Tabío, Michael P ; Beurel, Eléonore ; Han, Dongmei ; Medina-Rodriguez, Eva M ; O'Connor, Gregory ; Daunert, Sylvia ; Zeltzer, Shanie E

Chronic stress often has deleterious effects leading to the development of psychiatric diseases. The gut-brain axis represents a novel avenue for stress research. The negative effects of stress on the gut physiology have been well-described, whereas the pathways whereby stress controls microbial composition to modulate behaviors remains mainly unknown. We discovered that vasoactive intestinal peptide (VIP) activation promoted stress-induced microbial changes leading to increased infiltration of T helper (Th) 17 cells and microglial activation in the hippocampus and depressive-like behaviors, uncovering a close crosstalk between intestinal VIPergic release and the gut microbiota during stress and providing a new interaction between the nervous system and the gut microbiome after stress. Neutralization of the signature cytokine of Th17 cells, interleukin (IL)-17A, was sufficient to block depressive-like behaviors, reduce neuronal VIPergic activation and microglia activation induced by VIPergic activation after stress, opening new potential therapeutic targets for depression.

2025-01-01·Journal of Ethnopharmacology

Shaoyao decoction alleviates DSS-induced colitis by inhibiting IL-17a-mediated polarization of M1 macrophages

Article

作者: Wang, Shiying ; Zhang, Haiyan ; Ma, Yanyan ; Cai, Linkun

ETHNOPHARMACOLOGICAL RELEVANCEThe efficacy of Shaoyao decoction (SYD), a traditional Chinese medicine prescription, in alleviating colonic mucosal inflammation in ulcerative colitis (UC) has been established. However, the specific mechanism underlying the therapeutic effects of SYD on UC is not clear.AIM OF STUDYIn this study, we demonstrated the therapeutic effect of SYD on the polarization of M1 macrophages and elucidated the underlying mechanism.MATERIALS AND METHODSUC mice were induced with 3% DSS for one week and subsequently treated with SYD for another week. The composition of SYD was determined by HPLC. To assess the therapeutic efficacy of SYD, key parameters, including body weight changes, DAI scores, colon length, and histological alterations in colonic tissues, were monitored. ELISA was performed to quantify inflammatory cytokines, while Western blotting and immunofluorescence analyses were performed to quantify tight junction protein expression and M1 macrophage infiltration, respectively. Functional assessments focused on lysosomal activity and glucose oxidation in primary macrophages and RAW 264.7 cells exposed to LPS, IL-17a, and SYD using dedicated kits. To elucidate the mechanisms underlying the action of SYD, the data derived from TMT-based proteomics were analyzed to screen and predict its potential targets and regulated pathways.RESULTSAfter treatment for seven days, SYD significantly mitigated colitis symptoms in mice, as determined by a decrease in body weight loss, an increase in colon length, and a decrease in disease activity index (DAI) score. The results of histopathological analysis showed substantial improvements in the integrity of colonic tissue. Additionally, SYD treatment significantly decreased the levels of proinflammatory cytokines, including IL-17a, IL-6, IL-1β, and TNF-α. This effect was accompanied by a reduction in the infiltration of CD86⁺ macrophages and restoration of occludin and ZO-1 levels, thus improving colonic mucosal permeability. SYD treatment also reversed the upregulation of cathepsin (CTS) E, CTSS, lysosomal-associated membrane protein (LAMP)-1, and LAMP-2 expression observed in CD86⁺ macrophages and RAW 264.7 cells treated with IL-17a. These changes were accompanied by an increase in lysosomal acidification and the enzymatic activities of CTSE and CTSS, suggesting that SYD can restore lysosomal function. SYD also corrected the metabolic alterations in M1 macrophages, characterized by an increase in the extracellular acidification rate (ECAR) and a decrease in oxygen consumption rate (OCR). This was confirmed by a decrease in the ADP/ATP ratio, downregulation of pyruvate dehydrogenase kinase 4 (PDK4) and lactate dehydrogenase (LDH) expression, and a decrease in the concentrations of intracellular pyruvate and lactate. These findings showed that SYD promotes glucose oxidation in macrophages. The data derived from TMT-based proteomics showed that the PPAR pathway was a key target in regulating the polarization of M1 macrophages. SYD was also found to regulate the expression of the PPAR-α, PPAR-γ, and PPAR-δ proteins.CONCLUSIONSYD inhibited the polarization of M1 macrophages induced by IL-17a. This effect occurred due to the restoration of lysosomal activity and glucose oxidation via activation of the PPAR/NF-κB pathway. Our findings provided novel insights into the mechanisms underlying the therapeutic effects of SYD in UC.

843

项与 IL-17A 相关的新闻（医药）

2024-10-31

·药精通Bio

22.5亿美元！诺华青睐的VAV1分子胶长啥样？市场前景如何？

IND2025主会场授课已被预定，大会第一天下午茶歇前授课时间段预定开始，咨询热线：177 0186 0390。点击图片，查看IND2024会后报告资讯 2024 年 10 月 28 日，Monte Rosa Therapeutics宣布了一项全球独家开发和与诺华公司签订商业化许可协议，以推进 VAV1 MGD，包括 MRT-6160。MRT-6160 目前正在进行针对免疫介导疾病的 1 期单次递增剂量 (SAD)/多次递增剂量 (MAD) 健康志愿者研究。根据协议条款，诺华将获得 MRT-6160 和其他 VAV1 MGD 的开发、制造和商业化的全球独家权利，并将负责从 2 期临床研究开始的所有临床开发和商业化。Monte Rosa 仍负责完成正在进行的 MRT-6160 1 期临床研究。 MRT-6160 是一种有效的、高选择性的、口服生物可利用的研究性 VAV1 降解剂，VAV1 是 T 细胞和 B 细胞受体下游的关键信号蛋白。临床前研究表明，VAV1 深度降解，导致与免疫介导病症相关的细胞因子显著减少，而对其他蛋白质没有可检测到的影响。MRT-6160 在多种免疫介导疾病的临床前模型中显示出有希望的活性。根据协议条款，诺华同意向 Monte Rosa 预付 1.5 亿美元。从第二阶段研究开始，Monte Rosa 有资格获得高达 21 亿美元的开发、监管和销售里程碑，以及美国以外净销售额的分级特许权使用费。Monte Rosa 将共同资助任何 3 期临床开发，并将分享与 MRT-6160 在美国制造和商业化相关的任何利润和损失。目前MRT-6160的I期SAD/MAD研究正在进行中，临床数据预计于2025年第1季度获得。关于VAV1分子胶的相关背景信息本公众号早有介绍【研发前沿|分子胶的理性设计(2)——CDK2分子胶与Monte Rosa的野望】、【分子胶的理性设计(3)：Monte Rosa教你如何“调教”CRBN】，今年的分子胶行业总结报告中，也对此简要介绍过。不过一直未曾对此做过详尽报道，这里做个总结与补充。关于VAV1的生物学背景早在今年8月，Monte Rosa在Trends in Immunology上发文报道了VAV1的相关生物学背景（DOI: 10.1016/j.it.2024.06.004），表明转录因子VAV 1作为一种“undruggable”蛋白，是原代人CD4+和CD8+T细胞中T细胞受体（TCR）活化和细胞因子产生的关键正调节剂;数据表明VAV1的丧失/抑制调节自身免疫和炎症;以及来自T和T/B细胞介导的关节炎和结肠炎疾病模型的有希望的临床前数据，显示通过蛋白质降解的选择性VAV1靶向的有效性。 VAV 1在抗原受体信号转导中扮演着关键角色 VAV 1的核心鸟嘌呤核苷酸交换因子（GEF）依赖性功能 VAV1 是经多次验证的T细胞和B细胞受体下游的关键支架蛋白和信号分子。VAV1敲除能阻断T细胞介导的B细胞活性(IL-17A, IL-17F, IL-6, IL-2, TNF, sIgG)。 VAV1分子胶的商业价值近年来靶向治疗的出现为自身免疫性疾病和慢性炎症性疾病的治疗带来了突破，例如像炎症性肠病、类风湿性关节炎、脊柱关节炎和银屑病等，但仍存在着许多未满足的临床需求。目前，针对自身免疫性疾病和慢性炎症性疾病的治疗策略主要包括生物制剂和口服小分子药物，然而，治疗失败、药物耐受性差、对糖皮质激素依赖以及缺乏针对某些疾病的靶向治疗等问题仍未得到解决。现有的治疗方案，例如生物制剂，在治疗某些疾病方面疗效显著，但它们通常为注射剂，且存在免疫原性等问题。而口服小分子药物尽管易于给药，但由于其靶点通常位于细胞内，限制了其作用范围。此外，现有的靶向治疗药物往往仅能抑制单一蛋白或信号通路，疗效并不理想。因此，研发更多针对自身免疫性疾病和慢性炎症性疾病的新型药物，尤其是那些能够靶向多个重要信号通路，并具有安全性和有效性的药物，依然是未来研究的重要方向。相比于上述疗法存在的缺陷，VAV1分子胶的优势主要体现在以下几个方面：靶向性强: VAV1 主要表达在造血细胞中，包括 T 细胞和 B 细胞，因此针对 VAV1 的分子胶可以更有效地抑制免疫反应，减少对其他器官和组织的损伤。多重作用机制: VAV1 作为一种双功能蛋白，同时具有 GEF 活性和支架蛋白功能。VAV1 分子胶通过降解 VAV1 蛋白，可以同时抑制其 GEF 活性和支架蛋白功能，从而阻断 T 细胞和 B 细胞的多种重要信号通路，更全面地抑制免疫反应。有效性高: 已有研究表明，VAV1 分子胶在多种自身免疫性疾病动物模型中展现出良好的治疗效果，例如在关节炎和结肠炎模型中，VAV1 分子胶能够显著减轻炎症反应，改善组织损伤。总之，VAV1 分子胶作为一种新型的靶向治疗药物，具有靶向性强、多重作用机制和有效性高三大优势，有望成为治疗自身免疫性疾病和慢性炎症性疾病的新希望。 Monte Rosa也在文章中列出了现有自免疗法的相关机制与药物发展态势，VAV1分子胶具有独特的机制，具有广泛的潜在应用潜力，可通过安全的口服治疗解决多种自身免疫性疾病。实验研究也表明了VAV1分子胶对于T细胞介导的B细胞活化具有更选择性且更为高效的阻断活性。至于VAV1体内药效： MRT-6160改善T细胞转移诱导的结肠炎优于标准疗法。 MRT-6160减少溃疡性结肠炎T细胞转移模型中炎症介导的结肠损伤和细胞因子产生 MRT-6160抑制风湿性关节炎疾病模型中的疾病进展、关节炎症和自身抗体产生，同样优于标准疗法 MRT-6160在T细胞介导的多发性硬化自身免疫疾病模型中引发剂量依赖性活性 Monte Rosa因此对这个项目具有很高的期望，认为其是多种自身免疫性疾病的口服替代疗法，有望对目前千亿美元的自免药物市场带来强有力的冲击。 MRT-6160长啥样到了最关键的环节，Monte Rosa的VAV1分子胶MRT-6160的具体结构长啥样？其实结合公开Poster信息与专利（WO2024151547A1），很容易便能猜到。首先是MRT-6160的降解活性：DC50 = 7 nM，Dmax = 97%。专利中是什么情况呢？这里偷懒借用之前报告中的内容，显而易见了，通过活性数据，简单的SAR分析，以及成药性判断，Cpd.185，极大概率便是MRT-6160的具体结构。后话此前也提到过，VAV1是与GSPT1的G-loop表面高度相似性的靶点。VAV1分子胶的发现依赖于Monte Rosa的QUEEN平台，基于AI+结构生物学所开发的，是真正的AIDD药物。更惊人的是大善人在GitHub上对这个项目做了开源，感兴趣的可以拿来跑一下，助力发现新的VAV1分子胶。第一次关注VAV1分子胶始于去年7月份，长久以来看好的项目终于通过诺华的这笔交易得到了初步证实，还是很让人欣慰的。期待将来的临床结果进一步证实这一点。 END 免责声明：本文仅作知识交流与分享及科普目的，不涉及商业宣传，不作为相关医疗指导或用药建议。文章如有侵权请联系删除。 OTC2024类器官前沿应用与3D细胞培养论坛圆满落幕，点击图片可查看会后报告，咨询OTC2025类器官论坛请联系：王晨 180 1628 8769

临床3期临床1期临床2期临床申请细胞疗法

2024-10-31

·药时代

国产自免新药之光！恒瑞的「夫那奇珠单抗」疗效到底怎么样？

前言银屑病，也俗称为“牛皮癣”，发病机制复杂，涉及神经、内分泌及免疫系统。由于典型的红色斑块常出现在头部、手部及四肢等易暴露部位，患者往往会面临来自社会、心理等多方面的压力。目前，我国银屑病患者约700多万，其中有57.3%为中重度银屑病患者。 2024年8月20日，首个本土自研靶向IL-17A的中重度银屑病创新药——夫那奇珠单抗注射液（vunakizumab，SHR-1314）获NMPA批准上市。夫那奇珠单抗为恒瑞医药自研产品，既是国内首个获批的本土自主研发重组抗IL-17A人源化单抗，也是恒瑞在自身免疫疾病领域上市的首个创新药！夫那奇珠单抗的上市打破了同类进口药物的长期垄断局面，为400余万中重度银屑病患者提供了新的治疗选择。那么夫那奇珠单抗的疗效到底怎么样，比起进口药效果又如何？ III期临床详细结果公布：SHR-1314-301研究解析夫那奇珠单抗的获批上市基于一项在全国开展的III期SHR-1314-301研究。2024年10月19日，该研究完整分析结果在皮肤病领域权威期刊Journal of the American Academy of Dermatology（美国皮肤病学会杂志，IF=12.8）上发布，题为“Efficacy and safety of vunakizumab in moderate-to-severe chronic plaque psoriasis: a randomized, double-blind, placebo-controlled phase 3 trial”，文章详尽介绍了SHR-1314-301研究的全部结果。 SHR-1314-301研究为随机对照试验，包括52周的双盲治疗期（12周的核心期治疗+40周的维持治疗）和16周的安全随访期。研究共纳入690例成人中重度斑块状银屑病患者。这690例患者被2:1随机分入试验组和安慰剂组，其中试验组先是每两周（第0，2，4周）注射240mg夫那奇珠单抗注射液，之后按此剂量每4周给药一次；安慰剂组前12周用药频率和试验组一致，第12周时转为夫那奇珠单抗240mg治疗（240mg Q2W*3+240mg Q4W）。研究的主要终点为：1）第12周银屑病面积和严重程度指数（PASI）评分比基线至少改善90%（PASI 90）的受试者比例；2）第12周时达到静态医师全面评估（sPGA）0/1的受试者比例。次要终点包括第12周PASI 75/PASI 100的受试者比例、sPGA 0的受试者比例等。从试验设计来看，安慰剂组在12周后转为接受夫那奇珠单抗治疗，这样设计不仅可评估疗效，同时保证了所有受试者都得到治疗。另外，两个主要终点标准的选择也符合相关治疗指南中的疾病治疗要求。《中国银屑病诊疗指南（2023版）》中指出，患者若能达到PASI 90/PASI 100则实现了症状和皮损的完全清除或几乎完全清除。另一主要终点sPGA 0/1的实现也意味着裸眼观察下，患者皮肤已完全/几乎全面恢复。且PASI90的实现与患者生活质量（QoL）改善密切相关。夫那奇珠单抗：银屑病治疗新星在银屑病治疗领域，生物制剂正得到更多重视。《中国银屑病诊疗指南（2023版）》明确指出，对于接受光疗或传统系统治疗无效、失效或无法耐受且生活质量受到明显影响的患者，可考虑应用生物制剂。目前在我国正式获批用于斑块状银屑病治疗的生物制剂包括TNF-α抑制剂、IL-23抑制剂和IL-17A抑制剂等。其中，IL-17A作为银屑病核心致病因子，其生物制剂在银屑病治疗中脱颖而出。在夫那奇珠单抗获批上市前，国内获批用于银屑病治疗的IL-17A药物均为进口药。其中，司库奇尤单抗（Secukinumab ）和依奇珠单抗（Ixekizumab）分别于2019年4月和9月作为第一批临床急需境外新药在中国获批上市。从此次披露的SHR-1314-301详细数据来看，相比于此前获NMPA批准用于银屑病治疗的IL-17A产品，夫那奇珠单抗注射液显示出了毫不逊色的治疗表现，是一款疗效强、起效快、作用持久的银屑病新药。 1）疗效强研究结果显示，12周时，试验组显示出更高的PASI 90（76.8% vs 0.9%）和sPGA 0/1（71.8% vs 0.4%）应答率，研究达到所有主要终点。且相比于安慰剂组，试验组其余各项评分均显著改善。数据显示，试验组12周时达到PASI 75和PASI 100的受试者比例为93.6%和36.6%，安慰剂组分别为4.0%和0.0%。且试验组显示出更高的sPGA 0（38.2%vs0.0%），研究达到所有关键次要终点。而根据司库奇尤单抗III期ERASURE和FIXTURE研究结果，其第12周时PASI 75应答率为77.1%-81.6%、PASI 90应答率为54.2%-59.2%和PASI 100应答率为24.1%-28.6%。另一边，依奇珠单抗III期UNCOVER-1, 2, 3研究数据显示，其第12周时PASI 75应答率为87.3%-89.7%，PASI 90应答率为68.1%-70.7%，PASI 100应答率为35.3%-40.5%，sPGA 0/1应答率为80.5%-83.2%。虽并非头对头研究数据，但分析对比三款药物关键临床试验设计情况，此对比结果具有一定参考价值。另从患者入组标准来看，SHR-1314-301研究中，基线时sPGA >4的受试者比例为58.8%，另两款IL-17单抗关键临床试验中此数值为46%-52%。可更直接地理解为，SHR-1314-301研究中纳入了更高比例的重度银屑病患者，这意味着哪怕最终指标应答率相当，但SHR-1314-301研究中可能面临更大的挑战。且值得注意的是，12周的核心治疗期内，SHR-1314-301研究给药频率更低（4次vs 6次）。 2）起效快夫那奇珠单抗的另一个特点是起效快。此次发布的详细研究数据显示，试验组在治疗第2周时，PASI评分平均百分比减少超过50%，到第4周时56.6%的受试者实现PASI 75。且PASI 90应答中位时间仅8.3周（95%CI, 8.1-8.3周）。 3）作用持久从试验组实现PASI 90/sPGA 0/1的受试者比例变化情况来看（见下图蓝色线），在12周核心治疗期内，试验组的两组曲线均迅速爬升至较高点，这表明大部分患者在12周内症状就已经良好改善。进入维持期后，两组曲线趋于平稳，且52周时并未表现出明显下滑趋势，这足以证明夫那奇珠单抗在中重度银屑病治疗中持久的作用效果。 A:52周内达到PASI 90的患者比例随时间变化情况 B:52周内达到sPGA 0/1的患者比例随时间变化情况图片源自：Efficacy and safety of vunakizumab in moderate-to-severe chronic plaque psoriasis: a randomized, double-blind, placebo-controlled phase 3 trial 更多详细数据显示，在维持期，超过85%的受试者持续保持了PASI 75、PASI 90或sPGA 0/1应答，与此前已经获批的依奇珠单抗和司库奇尤单抗III期研究结果相当。此外在安全性方面，夫那奇珠单抗组的不良事件发生率与安慰剂组相似，且感染发生率低，无受试者因为注射部位反应而停止治疗或终止研究。总体而言，夫那奇珠单抗的安全性与已获批的依奇珠单抗和司库奇尤单抗相当，没有发现新的安全性信号。结语据悉，使用夫那奇珠单抗全年仅需注射14次，预充式自动注射笔的应用也使患者给药更为便捷。恒瑞官方公众号消息显示，在收到上市批件后，满载夫那奇珠单抗注射液的冷藏车就马不停蹄地驶向全国医院和药房，并于8月30日上午由复旦大学附属华山医院徐金华教授开出全国首张处方。目前，恒瑞医药已就夫那奇珠单抗开展多项临床试验，预计这款药将有望惠及更多年龄段，更多疾病领域的其他患者！参考资料： 1.Efficacy and safety of vunakizumab in moderate-to-severe chronic plaque psoriasis: a randomized, double-blind, placebo-controlled phase 3 trial. 2.《中国银屑病诊疗指南（2023版）》 3.恒瑞医药官方公众号 4.其他公开资料点击了解更多！

临床结果临床3期上市批准

2024-10-31

·药时代

替尔泊肽大卖110亿美元，礼来股价暴跌

2024年10月30日，礼来公布Q3财报，因营收与利润均未达预期，公司下调了全年调整后利润预期。财报显示，礼来Q3营收114.4亿美元，低于市场预期的121.1亿美元；净利润为9.7亿美元，摊薄到每股为1.18美元，远低于市场预期的每股1.47美元。礼来无奈将今年的营收预期从460亿美元下调至466亿美元，而礼来今年曾两次上调销售额预期。受此消息影响，礼来股价早盘大跌逾10%，盘后收跌6.28%。截止日前，礼来仍是全球市值最高的纯药企，自2023年以4000亿美元问鼎以来，市值一路飙升近9000亿美元，超过了中国A股所有生物医药上市公司市值总和。本次营收利润双双下滑，其主要原因便来源于替尔泊肽的销售不佳。替尔泊肽是礼来最重磅产品之一，分为降糖版Mounjaro与减重版Zepbound两款。第三季度，Mounjaro销售收入31.1亿美元，相较去年同期实现翻倍增长；Zepbound销售收入12.6亿美元，低于此前分析师预期的17亿美元。礼来将其归因于产能受限，并宣布持续拓展产量。虽然低于市场预期，但不可忽视的是替尔泊肽放量迅速，上市仅一年销售额便达50亿美元，今年前三季度销售额更是已达110亿美元，正式踏入“超级重磅炸弹”之列。不少业内人士将其与诺和诺德的司美格鲁肽相比较，认为两者将逐出未来新药王，司美格鲁肽今年上半年销售额为130亿美元。此外，礼来在本季度财报中还停掉了三条管线。包括口服小分子IL-17a抑制剂DC-806；PD-1激动剂抗体Peresolimab以及一款用于心血管疾病的APOC3 siRNA。其中，DC-806是2023年礼来溢价40% ，总计24亿美元收购DICE Therapeutics所得。当时，礼来还获得了另一款Fast-follow, 改善活性与药代的DC-853，本次礼来移除DC-806，全力支持DC-853。至于Peresolimab，是目前全球进展最快的PD-1激动剂抗体。2023年，礼来公布其用于治疗难治性类风湿关节炎（RA）的2a期临床试验结果阳性。此次突然宣布移除也并不使人意外，默沙东、BMS、吉利德等MNC都曾通过收并购的方式获得过PD-1激动剂抗体，但结果大多是杳无音信，或终止开发。回到礼来今年Q3财报，不知替尔泊肽的销售放缓，会对GLP-1领域的投资及研发热度产生何种影响？封面图来源：pixabay 版权声明/免责声明本文为原创文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢! 药时代官方网站:www.drugtimes.cn 联系方式: 电话:13651980212 微信:27674131 邮箱:contact@drugtimes.cn 礼来公布「重磅自免药物」长期数据，对战强生、艾伯维！诺华向你发送一条新消息：聚梦成就非凡，一起启程创想！保二冲一，ROCK2抑制剂为何能连续冲击cGVHD治疗前线？点击查看更多精彩！

财报siRNA临床3期临床2期引进/卖出