更新于：2024-11-01

IL-17F

更新于：2024-11-01

基本信息

别名

Cytokine ML-1、IL-17F、IL17F

+ [4]

简介

Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:21350122). IL17A-IL17F signals via IL17RA-IL17RC heterodimeric receptor complex, triggering homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter through SEFIR domains. 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:18684971, PubMed:21350122, PubMed:11591732, PubMed:11591768, PubMed:17911633, PubMed:11574464, PubMed:28827714). IL17A-IL17F is primarily involved in host defense against extracellular bacteria and fungi by inducing neutrophilic inflammation (By similarity). As signature effector cytokine of T-helper 17 cells (Th17), primarily induces neutrophil activation and recruitment at infection and inflammatory sites (By similarity). Stimulates 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). IL17F homodimer can signal via IL17RC homodimeric receptor complex, triggering downstream activation of TRAF6 and NF-kappa-B signaling pathway (PubMed:32187518). Via IL17RC induces transcriptional activation of IL33, a potent cytokine that stimulates group 2 innate lymphoid cells and adaptive T-helper 2 cells involved in pulmonary allergic response to fungi. Likely via IL17RC, promotes sympathetic innervation of peripheral organs by coordinating the communication between gamma-delta T cells and parenchymal cells. Stimulates sympathetic innervation of thermogenic adipose tissue by driving TGFB1 expression (By similarity). Regulates the composition of intestinal microbiota and immune tolerance by inducing antimicrobial proteins that specifically control the growth of commensal Firmicutes and Bacteroidetes (By similarity).

关联

项与 IL-17F 相关的药物

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

Sonelokimab

索洛奇单抗

靶点

IL-17A x IL-17F x albumin

作用机制

IL-17A抑制剂 [+3]

在研机构

MoonLake Immunotherapeutics [+1]

原研机构

Ablynx NV

在研适应症

银屑病关节炎 [+5]

非在研适应症

慢性大斑块银屑病

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期1800-01-20

Recombinant human IL-17A/F humanized antibody(Livzon Pharmaceutical Group)

重组抗人IL-17A/F人源化单克隆抗体 (丽珠医药集团)

靶点

IL-17A x IL-17F

作用机制

IL-17A抑制剂 [+1]

在研机构

北京鑫康合生物医药科技有限公司 [+2]

原研机构

丽珠医药集团股份有限公司

在研适应症

强直性脊柱炎 [+1]

非在研适应症-

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期1800-01-20

项与 IL-17F 相关的临床试验

NCT06641089 / Not yet recruiting临床3期

A Phase 3, Parallel-group, Randomized, Double-blind, 4-arm, Placebo-controlled, Multicenter Study with Risankizumab As Active Reference Arm, to Investigate the Efficacy and Safety of Subcutaneous Sonelokimab in Male and Female Participants Aged 18 Years and Over with Active Psoriatic Arthritis and Previous Inadequate Response or Intolerance to Tumor Necrosis Factor-α Inhibitors

This is a study to confirm the clinical efficacy and safety of sonelokimab compared with placebo in the treatment of adults with active psoriatic arthritis who have had a previous inadequate response or intolerance to anti-tumor necrosis factor (TNF)α therapy.

开始日期2024-10-15

申办/合作机构

MoonLake Immunotherapeutics

NCT06641076 / Not yet recruiting临床3期

A Phase 3, Parallel-group, Randomized, Double-blind, 3-arm, Placebo-controlled, Multicenter Study to Investigate the Efficacy and Safety of Subcutaneous Sonelokimab in Male and Female Participants Aged 18 Years and Over with Active Psoriatic Arthritis Who Are Naive to Biologic DMARDs

This is a study to demonstrate the clinical efficacy and safety of sonelokimab administered subcutaneously compared with placebo in the treatment of adult patients with active psoriatic arthritis who are naive to biologic disease-modifying antirheumatic drug therapy.

开始日期2024-10-15

申办/合作机构

MoonLake Immunotherapeutics

NCT06624228 / Not yet recruiting临床3期

A Multicenter, Randomized, Double-Blind, Risankizumab-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Bimekizumab in Adult Study Participants With Active Psoriatic Arthritis

The purpose of the study is to compare the efficacy of bimekizumab versus risankizumab after 16 weeks of treatment in study participants with active psoriatic arthritis (PsA).

开始日期2024-09-30

申办/合作机构

UCB Biopharma SRL

100 项与 IL-17F 相关的临床结果

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100 项与 IL-17F 相关的转化医学

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0 项与 IL-17F 相关的专利（医药）

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1,815

项与 IL-17F 相关的文献（医药）

2024-12-31·Journal of Medical Economics

The cost-effectiveness of a bimekizumab versus IL-17A inhibitors treatment-pathway in patients with active axial spondyloarthritis in Scotland

Article

作者: Lyris, Nikos ; Rose, Micah ; Taieb, Vanessa ; Mørup, Michael F ; Willems, Damon ; Gerlier, Laetitia ; Lamotte, Mark ; Thom, Howard

OBJECTIVETo estimate the cost-effectiveness of a treatment-pathway initiated with bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A, in patients with axial spondyloarthritis (axSpA) compared with IL-17Ai's, ixekizumab, and secukinumab, from the NHS Scotland perspective.METHODSThe axSpA treatment-pathway was modeled using a decision tree followed by a lifetime Markov model. The pathway included first- and second-line biologic disease-modifying antirheumatic drugs (bDMARD), followed by best supportive care (bDMARD, nonbiologic). Bimekizumab followed by any bDMARD ("BKZ") was compared with IL-17Ai's: secukinumab 150 mg followed by a blend ("SEC") of dose up-titration to secukinumab 300 mg and any bDMARD, or ixekizumab followed by any bDMARD ("IXE"). Transition to the next therapy was triggered by Bath Ankylosing Spondylitis Disease Activity Index-50% (BASDAI50) non-response or any-cause discontinuation. A published network meta-analysis provided efficacy data. EuroQoL-5-dimensions utilities were derived by mapping from Ankylosing Spondylitis Disease Activity Score. Costs included disease management (linked to functional limitations), biologics acquisition (list prices), administration and monitoring (NHS 2021/22). Discounting was 3.5%/year. Probabilistic results from patients with non-radiographic axSpA and ankylosing spondylitis were averaged to reflect the axSpA disease spectrum. Scenario and sensitivity analyses were performed.RESULTSThe incremental cost-effectiveness ratio (ICER) of BKZ was £24,801/quality-adjusted life-year (QALY) vs. SEC (95% credible interval £24,163-£25,895). BKZ had similar costs (Δ -£385 [-£15,239-£14,468]) and QALYs (Δ 0.039 [-0.748-0.825]) to IXE, with £1,523 (£862-£2,222) net monetary benefit. Conclusions remained unchanged in most scenarios. Results' drivers included BASDAI50 response rate and disease management cost.LIMITATIONSResults were based on list prices. Data concerning up-titration to secukinumab 300 mg was scarce.CONCLUSIONSThe bimekizumab treatment-pathway represents a cost-effective option across the axSpA disease spectrum in Scotland. Bimekizumab is cost-effective compared to a secukinumab-pathway that includes dose up-titration, and has similar costs and QALYs to an ixekizumab-pathway.

2024-12-01·Molecular Biology Reports

Tumor necrosis factor alpha induced protein 3, interleukin 10, tumor necrosis factor alpha, and interleukin 17 F genes polymorphisms in Algerian patients with rheumatoid arthritis

Article

作者: Bouguerra-Aouichat, S ; Zaoui, D ; Salah, S S ; Abbadi, M ; Benahmed, D ; Boukouaci, W ; Hamoudi, H Ait

BACKGROUNDRheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation. Its pathogenesis involves immunological, genetic, and environmental factors. We investigate the association between Tumor Necrosis Factor α Protein 3 (TNFAIP3), Interleukin 10 (IL10), Tumor Necrosis Factor α (TNF α), and Interleukin 17 F (IL17F) polymorphisms with susceptibility to RA.METHODS AND RESULTS191 patients with RA diagnosed according to the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) classification and 190 healthy subjects were recruited. Rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPA), and C-reactive protein (CRP) were measured. Genotyping of the polymorphisms was performed by real-time PCR. Analysis of the allelic frequencies of TNFAIP3 showed a positive association OR (95% CI) = 1.46 (1.01-2.09); p = 0.04, but failed to meet the criteria of significance after Bonferroni Correction. The genotypic and allelic distribution of the IL10, IL17F, and TNFα showed no significant difference when comparing the RA group with controls. Furthermore, the genotype codominant model shows a moderate positive association in the presence of ACPA (OR (95% CI) = 2.82 (1.22-6.24); p = 0.01. None of the polymorphisms studied was associated with RF and CRP production.CONCLUSIONOur results show that there is a tendency for the AG genotype of IL10-1082 to be associated with the production of ACPA in patients with RA. None of the variants studied were associated with RA susceptibility in Algerians.

2024-11-01·Journal of Immunological Methods

A novel whole blood assay to quantify the release of T cell associated cytokines in response to Bordetella pertussis antigens

Article

作者: Heininger, Ulrich ; Lambert, Eleonora E. ; Barkoff, Alex-Mikael ; Siena, Emilio ; Knuutila, Aapo ; van Els, Cecile ; Corbiere, Veronique ; Locht, Camille ; Read, Robert ; Kelly, Dominic ; Jobe, Haddijatou ; Buisman, Annemarie M. ; Saso, Anja ; Pagnon, Anke ; Mertsola, Jussi ; Diavatopoulos, Dimitri A. ; Kester, Kent E. ; Ochs, Martina M. ; Denoël, Philippe ; Blanc, Pascal ; van Dongen, Jacques J.M. ; de Jonge, Marien I. ; van Els, Cécile A.C.M. ; Clutterbuck, Elizabeth ; Orfao, Alberto ; Mills, Kingston H.G. ; Le Grand, Roger ; Teräsjärvi, Johanna ; van Gaans-van den Brink, Jacqueline A.M. ; Mascart, Françoise ; Bibi, Sagida ; Mielcarek, Nathalie ; Londoño-Hayes, Patricia ; Pollard, Andrew J. ; He, Qiushui ; Preston, Andrew ; Pinto, Marta Valente ; Gimenez-Fourage, Sophie ; Gorringe, Andrew ; De Montfort, Aymeric ; Fenwick, Craig ; Berbers, Guy ; Diavatopoulos, Dimitri ; Simonetti, Elles ; Huijnen, Martijn A. ; van der Most, Robbert G. ; de Groot, Ronald ; Sebo, Peter ; Pantaleo, Giuseppe ; Vecerek, Branislav ; Silerova, Marcela ; Roetynck, Sophie ; Kampmann, Beate

BACKGROUNDBordetella pertussis continues to cause whooping cough globally even in countries with high immunisation coverage. Booster vaccinations with acellular pertussis vaccines are thus used in children, adolescents, and adults. T cell immunity is crucial for orchestrating the immune response after vaccination. However, T cell assays can be expensive and difficult to implement in large clinical trials. In this study, a whole blood (WB) stimulation assay was developed to identify secreted T cell associated cytokines in different age groups after acellular pertussis booster vaccination.MATERIAL AND METHODSLongitudinal WB samples were collected from a small set of subjects (n = 38) aged 7-70 years participating in a larger ongoing clinical trial. For assay development, samples were diluted and incubated with purified inactivated pertussis toxin (PT), filamentous haemagglutinin (FHA), inactivated B. pertussis lysate, and complete medium (M) as stimulating conditions, with anti-CD28 and anti-CD49d as co-stimulants. Different timepoints around the vaccination (D0, D7, D14, D28), WB dilution factor (1:2, 1:4) and incubation time (24 h, 48 h, 72 h) were compared. Responses to 15 cytokines were tested with Luminex/multiplex immunoassay.RESULTSThe optimized assay consisted of WB incubation with M, PT, and FHA (including the two co-stimulants). After 48 h incubation, supernatants were collected for measurement of seven selected T cell associated cytokines (IL-2, IL-5, IL-10, IL-13, IL-17 A, IL-17F, and IFN-y) from samples before and 28 days after vaccination. PT stimulation showed a trend for upregulation of IL-2, IL-13, and IL-17 A/F for adult subjects, whereas the responses of all cytokines were downregulated for the paediatric subjects. Furthermore, PT and FHA-stimulated WB showed diverse cytokine producing profiles.CONCLUSIONSThe developed WB-based cytokine assay was shown to be less costly, easy to perform, and functional in differently aged individuals. Further, it requires only a small amount of fresh blood, which is beneficial especially for studies including infants. Our results support the use of this assay for other immunological studies in the future.

209

项与 IL-17F 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

2024-10-29

·Insight数据库

恒瑞「夫那奇珠单抗」新适应症获批，强直性脊柱炎

10 月 29 日，恒瑞「夫那奇珠单抗注射液」在国内获批新适应症，用于治疗强直性脊柱炎（AS）（CXSS2400019 )。截图来源：NMPA 官网 2024 年 8 月 27 日，夫那奇珠单抗获批用于治疗适合接受系统治疗或光疗的中重度斑块状银屑病成人患者。夫那奇珠单抗是恒瑞医药自主研发的一款重组人源化 IgG1 亚型抗 IL-17A 单克隆抗体, 保留了 0.8% 的鼠源成分，提高了 IL-17A 亲和力的同时降低了免疫原性。与已获批的司库奇尤单抗和依奇珠单抗相比，夫那奇珠单抗具有更高的 IL-17A 亲和力，有更强的阻断 IL-17A/IL-17R 的能力。已公布的夫那奇珠单抗治疗活动性强直性脊柱炎的 III 期临床研究结果显示：与安慰剂相比，夫那奇珠单抗 120 mg 组 16 周的 ASAS 20、ASAS 40、ASAS 5/6 应答率分别为 65.6%、46.3% 和 55.4%，显著优于安慰剂，并持续改善至第 32 周；夫那奇珠单抗 120 mg 组第 2 周 ASAS 20 应答率高于安慰剂（34.0% vs 11.6%，p<0.0001），且较安慰剂大幅改善总背痛 VAS 评分、晨僵及炎症指标等；同时，夫那奇珠单抗注射液在活动性 AS 患者中长期治疗的安全性、耐受性良好。目前，国内已批准 5 款 IL-17A 单抗，3 款进口，2 款国产。作用靶点上，其中比吉利珠单抗强效、选择性地中和 IL-17A 和 IL-17F，另外 4 款仅作用于 IL-17A。适应症上，除了赛立奇单抗，其他均被批准用于治疗 AS。国内已批准的 IL-17A 靶向药图片来源：Insight 数据库整理此外，目前国内还有多款在研 IL-17A 靶向药，除了 IL-17A 靶向新药，国内还有多款 IL-7A 靶向药生物类似药，如司库奇尤单抗生物类似药（BAT2306、CMAB015、SYS6012 等）、依奇珠单抗生物类似药 KH917。从研发进度上看，国内 IL-17A 靶向药即将进入收获期，多款进入临床 III 期。未来 IL-17A 靶向药领域的竞争势必更加白热化。封面来源：企业 Logo 免责声明：本文仅作信息分享，不代表 Insight 立场和观点，也不作治疗方案推荐和介绍。如有需求，请咨询和联系正规医疗机构。编辑：vvy PR 稿对接：微信 insightxb 投稿：微信 insightxb；邮箱 insight@dxy.cn 多样化功能、可溯源数据…… Insight 数据库网页版等你体验点击阅读原文，立刻解锁！

临床3期生物类似药上市批准

2024-10-29

·医药观澜

恒瑞医药1类新药新适应症获批，治疗强直性脊柱炎

▎药明康德内容团队报道今日（10月29日），中国国家药监局（NMPA）官网最新公示，恒瑞医药夫那奇珠单抗注射液新适应症上市申请已获得批准。公开资料显示，夫那奇珠单抗（SHR-1314）是恒瑞医药自主研发的重组抗IL-17A人源化单克隆抗体。该产品的首个适应症已经于今年8月在中国获批上市，治疗斑块状银屑病。本次是该产品在中国获批的第二项适应症，用于常规治疗疗效欠佳的活动性强直性脊柱炎成人患者。截图来源：NMPA官网 IL-17A在斑块状银屑病、银屑病关节炎和强直性脊柱炎的发病机理中起关键作用。IL-17A与IL-17F具有大于50％的结构同源性和重叠的生物学功能，二者在多种发炎的人体组织中均上调，并与其他促炎细胞因子例如肿瘤坏死因子（TNF）协同作用，放大炎症反应。根据恒瑞医药公开资料介绍，夫那奇珠单抗是一种靶向人IL-17A的重组人源化单克隆抗体，拟用于治疗与IL-17通路相关的自身免疫疾病，它可与IL-17A结合，阻断其与IL-17R的相互作用，导致下游炎性信号传导的阻断。该产品具有0.8%鼠源成分，保留了来自鼠源的6个CDR区，同时具有“创新结合表位”，从而保证了对IL-17A的高亲和力，能实现与IL-17A精准结合，高效靶向阻断IL-17A通路；同时较低的鼠源成分，也降低了潜在的免疫原性。根据恒瑞医药此前新闻稿介绍，夫那奇珠单抗本次获批的上市申请是基于一项多中心、随机、双盲、安慰剂对照的适应性无缝2/3期临床试验（SHR-1314-302）。研究表明，与安慰剂相比，夫那奇珠单抗注射液对活动性强直性脊柱炎具有统计学显著性和临床意义的改善。同时，SHR-1314注射液在活动性强直性脊柱炎患者中长期治疗的安全性、耐受性良好。强直性脊柱炎（AS）是一种慢性炎症性疾病，发病较为隐匿，患者多为逐渐出现腰背部或骶髂部疼痛和/或晨僵。本疾病主要侵犯骶髂关节、脊柱骨突、脊柱旁软组织及外周关节，严重者可发生脊柱畸形和强直，AS可伴发胸廓、肺、心脏、虹膜等多系统的关节外表现。此外大多数患者为青壮年，对患者的身心健康造成巨大影响。期待夫那奇珠单抗新适应症的获批，为更多的患者带来新的治疗选择。参考资料： [1] 2024年10月29日药品批准证明文件送达信息. From https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20241029152238114.html [2]恒瑞抗IL-17A夫那奇珠单抗强直性脊柱炎适应症上市申请获受理. Retrieved Feb 18 , 2024, from https://mp.weixin.qq.com/s/e_N9lvTlQtYS7T4WvWt0NQ [3]慢病创新里程碑！恒瑞首个自免创新药夫那奇珠单抗获批上市 Retrieved Aug 27 , 2024, from https://mp.weixin.qq.com/s/Tc7K1lf0I572Zzow6V0ZEA 本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈。转发授权及其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。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。

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