A Single-arm Open-label Study Assessing Short-term (Week 6, 16) and Long-term (Week 32) Efficacy of Guselkumab in Adult Participants With Pyoderma Gangrenosum

A single-arm open-label study assessing short-term (week 6, 16) and long-term (week 32) efficacy of guselkumab in adult participants with pyoderma gangrenosum (PG)

开始日期2025-01-01

申办/合作机构

Oregon Health & Science University

[+2]

NCT06611163 / Not yet recruiting临床3期

A Phase 3, Randomized, Double-blind, Placebo Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Subcutaneous Tildrakizumab in Subjects With Moderate to Severe Genital Psoriasis

Phase 3 study to evaluate the efficacy and safety of subcutaneous tildrakizumab in subjects with moderate to severe genital psoriasis.

开始日期2024-11-01

申办/合作机构

Sun Pharmaceutical Industries Ltd.

NCT06651489 / Not yet recruiting临床2期IIT

Efficacy of Guselkumab in the Treatment of Hailey Hailey Disease: An Open-label, Proof of Concept Study

Hailey-Hailey disease (HHD) is a debilitating genetic skin disorder, affecting mainly body folds with erythema and painful erosions and blisters. Histopathological findings include epidermal hyperplasia, suprabasilar clefting, dyskeratosis and acantholysis of keratinocytes. A final diagnosis of HHD is usually confirmed based on clinical and histopathological findings in line with genetic testing.
Several treatment options have been proposed for this chronic and disabling disorder, however, there is no reproducibly effective therapeutic for it.
The primary objective is to evaluate the treatment response of guselkumab. Single-center, non-randomized, single-arm, open-label, phase II trial to evaluate the efficacy and safety of guselkumab for the treatment of patients with HHD.

开始日期2024-11-01

申办/合作机构

Yale University

[+1]

100 项与 IL-23 相关的临床结果

登录后查看更多信息

100 项与 IL-23 相关的转化医学

登录后查看更多信息

0 项与 IL-23 相关的专利（医药）

登录后查看更多信息

13,388

项与 IL-23 相关的文献（医药）

2025-01-01·Journal of Affective Disorders

Causal effects of gut microbiota, metabolites, immune cells, liposomes, and inflammatory proteins on anorexia nervosa: A mediation joint multi-omics Mendelian randomization analysis

Article

作者: Bi, Tianyu ; Li, Zeyang

BACKGROUNDAnorexia nervosa (AN) is a significant psychological disorder influenced by environmental and genetic elements. Emerging research highlights the pivotal role of the gut microbiome in the development of diverse mental health conditions. This study aims to explore the causal effects and interactions of the gut microbiome, metabolites, immune cells, lipids, and inflammatory proteins on the risk of anorexia nervosa through mediation and multi-omics Mendelian Randomization (MR) analysis.METHODSThis study used data from the FinnGen genome-wide association study (GWAS) of AN (N = 402,625), integrated with GWAS data on 473 of gut microbiota (N = 5959), 233 metabolites (N = 136,016), 731 immune cells (N = 3757), 179 lipids (N = 7174), and 91 inflammatory proteins (N = 14,824). This study used the univariate MR (UVMR), mediation MR analysis, and sensitivity analysis to assess the potential causal associations between these biomarkers and AN.RESULTSThe inverse variance weighted (IVW) results suggest that 25 gut microbiota have causal effects on AN. Firmicutes E (OR: 0.294, 95 % CI: 0.107-0.806, P = 0.017), RUG147 (OR: 0.386, 95 % CI: 0.151-0.990, P = 0.048), CAG-977 (OR: 0.562, 95 % CI: 0.378-0.837, P = 0.005), Desulfobacterota A (OR: 0.651, 95 % CI: 0.466-0.909, P = 0.012), CAG-269 sp002372935 (OR: 0.673, 95 % CI: 0.483-0.937, P = 0.019), Klebsiella (OR: 0.684, 95 % CI: 0.566-0.827, P = 0.00009), Desulfovibrionia (OR: 0.706, 95 % CI: 0.538-0.926, P = 0.012), Klebsiella pneumoniae (OR: 0.737, 95 % CI: 0.600-0.906, P = 0.004), Desulfovibrionales (OR: 0.786, 95 % CI: 0.631-0.979, P = 0.031), CAG-776 (OR: 0.787, 95 % CI: 0.632-0.980, P = 0.032), Desulfovibrionaceae (OR: 0.788, 95 % CI: 0.635-0.978, P = 0.030). 13 gut microbiota were risk factors for AN, including Parachlamydiales (OR: 3.134，95%CI: 1.185-8.287, P = 0.021), Paenibacillus J (OR: 2.366，95%CI: 1.305-4.29, P = 0.005), Gillisia (OR: 1.947，95%CI: 1.135-3.339, P = 0.016), UBA1191 (OR: 1.856，95%CI: 1.221-2.822, P = 0.004), UBA7703 (OR: 1.843，95%CI: 1.032-3.289, P = 0.039), Faecalicatena sp002161355 (OR: 1.788，95%CI: 1.114-2.870, P = 0.016), Johnsonella ignava (OR: 1.742，95%CI: 1.031-2.944, P = 0.038), Staphylococcus aureus (OR: 1.614, 95%CI: 1.007-2.588, P = 0.047), Comamonas (OR: 1.522，95%CI: 1.004-2.307, P = 0.048), Ruminococcus D (OR: 1.24，95%CI: 1.050-1.464, P = 0.011), CAG-349 (OR: 1.198，95%CI: 1.048-1.370, P = 0.008), Ruminococcus D bicirculans (OR: 1.175，95%CI: 1.001-1.379, P = 0.048), CAG-177 (OR: 1.272，95%CI: 1.077-1.503, P = 0.005). Reverse MR analysis showed that causal effect of AN on 18 gut microbiota, but to a lesser extent. 12 metabolites have causal effects on AN. There are 7 protective factors, including glucose levels (OR: 0.700, 95%CI: 0.550-0.893, P = 0.004), isoleucine levels (OR: 0.769, 95%CI: 0.602-0.983, P = 0.036), phospholipids in large VLDL (OR: 0.856, 95%CI: 0.736-0.996, P = 0.044), total lipids in large VLDL (OR: 0.860, 95%CI: 0.740-0.999, P = 0.049), total lipids in small VLDL (OR: 0.863, 95%CI: 0.751-0.992, P = 0.038), free cholesterol in small VLDL (OR: 0.86, 95%CI: 0.752-0.996, P = 0.044), and free cholesterol in medium VLDL (OR: 0.866, 95%CI: 0.752-0.998, P = 0.047). There are 5 risk factors, including estimated degree of unsaturation (OR: 1.174, 95%CI: 1.009-1.367, P = 0.039), free cholesterol to total lipids ratio in small VLDL (OR: 1.199, 95%CI: 1.017-1.414, P = 0.031), phospholipids to total lipids ratio in small VLDL (OR: 1.216, 95%CI: 1.008-1.467, P = 0.041), total cholesterol levels in small HDL (OR: 1.241, 95%CI: 1.008-1.530, P = 0.042), and phospholipids to total lipids ratio in medium VLDL (OR: 1.280, 95%CI: 1.055-1.553, P = 0.012). Reverse MR analysis showed that AN had a causal effect on 15 metabolites. Mediation analysis reveals that the estimated degree of unsaturation mediates 0.69 % of the effect of Klebsiella pneumoniae on AN. Total lipids in small VLDL mediate 0.358 % of the effect of CAG-177 on AN, with a mediated proportion of 1.490 %. The mediation proportions for Estimated degree of unsaturation and Total lipids in small VLDL are relatively small. 36 immune cells have causal effects on AN. There are 7 protective factors, including Switched memory B cells %B cell (OR: 0.892，95%CI: 0.801-0.994, P = 0.038), CD127-CD8+ T cell absolute count (OR: 0.888，95%CI: 0.789-1.000, P = 0.049), IgD + CD24- B cell (OR: 0.917，95%CI: 0.862-0.975, P = 0.006), HVEM+ T cell (OR: 0.945，95%CI: 0.894-0.999, P = 0.045), CD40 + CD14 + CD16- monocyte (OR: 0.937，95%CI: 0.882-0.996, P = 0.038), CD64 + CD14 + CD16- monocyte (OR: 0.966，95%CI: 0.939-0.993, P = 0.016), CD8+ natural killer T cells (OR: 0.911，95%CI: 0.836-0.992, P = 0.032), HLA-DR+ T cells (OR: 0.921，95%CI: 0.866-0.980, P = 0.010), CD28-CD8+ T cells (OR: 0.886，95%CI: 0.792-0.991, P = 0.034). There are 26 risk factors. Reverse MR analysis showed that AN had a causal effect on 31 immune cells. AN increases the expression levels of five types of immune cells, including CD40 + CD14-CD16+ monocytes (OR: 1.087，95%CI: 1.004-1.177, P = 0.041), PDL-1+ CD14-CD16+ monocytes (OR: 1.082，95%CI: 1.002-1.168, P = 0.046), CD45+ CD33dim HLA-DR+ cells (OR: 1.145，95%CI: 1.019-1.287, P = 0.023), CD45+ basophils (OR: 1.164，95%CI: 1.036-1.307, P = 0.011), CD8+ natural killer T cells (OR: 1.102, 95%CI: 1.015-1.196, P = 0.020), and also decreases the expression levels of 26 immune cells. 6 liposomes showed exhibit protective effects against AN, including phosphatidylcholine (18:0_20:3) levels (OR: 0.852, 95%CI: 0.740-0.981, P = 0.026), phosphatidylcholine (O-18:2_18:1) levels (OR: 0.800, 95%CI: 0.672-0.952, P = 0.012), phosphatidylinositol (18:0_18:1) levels (OR: 0.873, 95%CI: 0.773-0.986, P = 0.029), phosphatidylinositol (18:1_18:2) levels (OR: 0.844, 95%CI: 0.734-0.971, P = 0.018), sphingomyelin (d38:1) levels (OR: 0.903，95%CI: 0.820-0.995, P = 0.039), and triacylglycerol (56:4) levels (OR: 0.786, 95%CI: 0.660-0.936, P = 0.007). There are 3 risk factors, including diacylglycerol (16:1_18:1) levels (OR: 1.208, 95%CI: 1.040-1.404, P = 0.014), phosphatidylcholine (18:1_18:3) levels (OR: 1.237, 95%CI: 1.003-1.526, P = 0.047), and phosphatidylinositol (16:0_20:4) levels (OR: 1.148, 95%CI: 1.003-1.314, P = 0.045). Reverse MR analysis showed that AN had a causal effect on 3 phosphatidylcholine (15:0_18:2) levels (OR: 1.075, 95%CI: 1.001-1.154, P = 0.048), phosphatidylcholine (O-16:2_18:0) levels (OR: 1.078, 95%CI: 1.002-1.159, P = 0.043), and triacylglycerol (51:1) levels (OR: 0.919, 95%CI: 0.850-0.994, P = 0.035). 6 inflammatory proteins have causal effects on AN, with protective factors including Glial cell line-derived neurotrophic factor levels (OR: 0.822，95%CI: 0.692-0.978, P = 0.027) and Interleukin-15 receptor subunit alpha levels (OR: 0.886, 95%CI: 0.789-0.995, P = 0.041) and risk factors including CC motif chemokine 4 levels (OR: 1.126, 95%CI: 1.011-1.254, P = 0.031), Interleukin-12 subunit beta levels (OR: 1.135, 95%CI: 1.033-1.248, P = 0.008), Monocyte chemoattractant protein-1 levels (OR: 1.152, 95%CI: 1.010-1.314, P = 0.035), and Sulfotransferase 1A1 levels (OR: 1.166, 95%CI: 1.006-1.351, P = 0.042). Reverse MR analysis showed that AN had a causal effect on Transforming growth factor-alpha (OR: 1.054，95%CI: 1.010-1.101, P = 0.016).CONCLUSIONSThis study used large-scale and novel GWAS data, for the first time reveals through mediation analysis and multi-omics MR analysis the roles of gut microbiota, metabolites, immune cells, lipids, and inflammatory proteins in the pathogenesis of AN. These findings provide new biomarkers and targets for further prevention and treatment strategies.

2025-01-01·Journal of Ethnopharmacology

Metabolic reprogramming and AMPK activation: Key players in the therapeutic effects of Cooling Blood and Detoxicating Formular on psoriasis

Article

作者: Yang, Danyang ; Li, Ping ; Meng, Yujiao ; Zhao, Jingxia ; Wang, Yazhuo ; Zhang, Xiawei ; Zhu, Haoyue ; Ma, Huike ; Wang, Yan ; Di, Tingting ; Chen, Jia ; Zhao, Ning ; Ma, Yueyue ; Qu, Baoquan ; Li, Lin

ETHNOPHARMACOLOGICAL RELEVANCECooling Blood and Detoxicating Formular (CBDF) based on the theory of cooling blood and dosing detoxification, is a useful traditional Chinese medicine (TCM) medication for psoriasis with blood-heat syndrome.AIM OF THE STUDYInvestigate the active constituents and mechanisms of the CBDF for the treatment of psoriasis.MATERIALS AND METHODSUPLC-Q-Orbitrap-HRMS technique was used to analyse the ingredients of CBDF absorbed into plasma and skin tissue. The therapeutic efficacy of CBDF was evaluated in treating an imiquimod (IMQ)-induced mouse model was assessed. Transcriptome analysis and gene enrichment analysis were used to explore the changes in gene expression and pathways following treatment with the CBDF. Validation was performed using western blotting, quantitative RT-PCR, flow cytometry, gene knockout and molecular docking in vitro and in vivo.RESULTS26 compounds were identified in the plasma of IMQ-induced psoriasis-like mouse with CBDF treatment, and higher levels of cimifugin in the lesion. CBDF improved the pathological changes of psoriasis, with inhibition of TNF-α, IL-23, and IL-17A and upregulation of IL-10. Gene enrichment analysis showed that the therapeutic effect of CBDF was related to AMPK pathway. In psoriasis lesions, the AMPK and fatty acid oxidation were suppressed, and glycolysis was enhanced. The Prkaa2, encoding AMPKα2 was down-regulated in psoriasis patients. CBDF inhibited glycolysis while stimulating fatty acid oxidation by the activating AMPK, thereby exerting an inhibitory effect on inflammation. CBDF inhibited MHCII, CD80, and CD86 on dendritic cells of skin drainage lymph node. In vitro, CBDF inhibited bone marrow-derived DCs secrete IL-23, TNF-α, and lactate, while enhanced fatty acid oxidation and AMPK activity. However, the therapeutic effect was weakened in AMPKα2 deletion. Additionally, psoriasis lesions and dendritic cells activation were significantly aggravated after AMPKα2 knockout. The key ingredients of the CBDF, cimifugin, rutin, astilbin, quercetin, and prim-O-glucosylcimifugin, all exhibit a notable affinity towards AMPKα2 binding.CONCLUSIONSCBDF ameliorates psoriasis symptoms and inhibit dendritic cells maturation by regulating metabolic reprogramming in an AMPK-dependent mechanism.

2024-12-31·Virulence

LGG promotes activation of intestinal ILC3 through TLR2 receptor and inhibits salmonella typhimurium infection in mice

Article

作者: Wang, Chunfeng ; Wang, Jiarui ; Wang, Junhong ; Zeng, Yan ; Cao, Xin ; Gao, Ming

Salmonella is a foodborne pathogen that causes disruption of intestinal mucosal immunity, leading to acute gastroenteritis in the host. In this study, we found that Salmonella Typhimurium (STM) infection of the intestinal tract of mice led to a significant increase in the proportion of Lacticaseibacillus, while the secretion of IL-22 from type 3 innate lymphoid cells (ILC3) increased significantly. Feeding Lacticaseibacillus rhamnosus GG (LGG) effectively alleviated the infection of STM in the mouse intestines. TLR2^-/- mice experiments found that TLR2-expressing dendritic cells (DCs) are crucial for LGG's activation of ILC3. Subsequent in vitro experiments showed that heat-killed LGG (HK-LGG) could promote DCs to secrete IL-23, which in turn further promotes the activation of ILC3 and the secretion of IL-22. Finally, organoid experiments further verified that IL-22 secreted by ILC3 can enhance the intestinal mucosal immune barrier and inhibit STM infection. This study demonstrates that oral administration of LGG is a potential method for inhibiting STM infection.

1,413

项与 IL-23 相关的新闻（医药）

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

·康方生物Akeso

全球首个CD47单抗实体瘤III期临床首例入组：依沃西联合莱法利一线治疗HNSCC（对比帕博利珠单抗）

Ivonescimab+AK117 近日，康方生物（9926.HK）宣布其自主研发的全球首创的PD-1/VEGF双特异性抗体依沃西联合新一代D47单抗莱法利（AK117）对比帕博利珠单抗一线治疗PD-L1阳性（CPS≥1）复发转移性头颈部鳞癌（R/M HNSCC）随机、对照、多中心、III期临床研究（AK117-302）完成首例患者入组。华中科技大学同济医学院附属协和医院杨坤禹教授和四川大学华西医院刘磊教授是该研究的共同主要研究者。 AK117-302研究是全球首个CD47单抗疗法治疗实体瘤的Ⅲ期临床研究。该研究是依沃西的第5项以PD-1/L1单抗疗法为阳性对照的Ⅲ期临床研究，也是依沃西第3项以帕博利珠单抗疗法为阳性对照III期临床研究。AK117-302研究体现了公司迭代当前肿瘤免疫治疗格局、建立全球更佳肿瘤标准治疗的决心和信心，也展现了康方生物通过科学的临床布局充分挖掘产品组合临床价值和商业价值的能力。流行病学数据显示，2022年头颈部肿瘤全球新发病例为77万，中国新发病例为8.4万，其中HNSCC占头颈部肿瘤的90%以上。R/M HNSCC患者5年生存率仅有3.6%。靶向和免疫治疗的获批推动了HNSCC临床治疗的发展，但中位总生存期（OS）仍不足一年。其中，帕博利珠单抗疗法已成为R/M HNSCC的一线标准治疗，是CSCO和NCCN指南首选推荐疗法。PD-1疗法改善了HNSCC的生存获益，但整体生存获益仍有限，部分患者反应不佳。临床亟待更高效的全新疗法的诞生，助力HNSCC患者获得长期生存获益。 ESMO 2024 此前，康方生物已在2024年欧洲肿瘤内科学会（ESMO）年会上报道了该联合疗法的优异疗效。结果显示，对于快速缩瘤需求特别高的HNSCC，莱法利联合依沃西方案具有优异的缩瘤效果和生存获益，取得了高于已披露PD-1研究的初步疗效数据，该疗法有望为HNSCC患者提供全新高效的免疫治疗方案。关于莱法利（AK117，CD47单抗）莱法利单抗是康方生物自主研发的新一代人源化lgG4 单克隆抗体，可与肿瘤细胞上表达的CD47结合，阻断CD47与其受体SIRPα的相互作用，增强吞噬细胞对肿瘤细胞的吞噬活性，从而抑制肿瘤生长。目前莱法利联合阿扎胞苷治疗血液瘤，莱法利单药或联合依沃西和卡度尼利治疗多种实体瘤的II期临床研究正在高效开展，初步研究疗效数据优异，未观察到剂量限制性毒性事件，表现出优越的安全性。莱法利联合依沃西对比帕博利珠单抗一线治疗PD-L1阳性头颈鳞癌的III期临床研究（AK117-302）完成首例患者入组，联合维奈克拉和阿扎胞苷一线治疗unfit AML的中国II期临床研究、莱法利治疗MDS的国际多中心II期临床研究均在入组中。关于依达方® （PD-1/VEGF双抗，依沃西）依达方®（依沃西单抗注射液）是康方生物自主研发的、全球首创PD-1/VEGF双特异性肿瘤免疫治疗药物。依达方®于2024年5月获得中国国家药品监督管理局批准上市，用于EGFR-TKI治疗进展的局部晚期或转移性nsq-NSCLC，成为全球首个获批上市的“肿瘤免疫+抗血管生成“协同抗肿瘤机制的双特异性抗体新药。目前，依达方®单药对比帕博利珠单抗单药一线治疗PD-L1表达阳性的晚期NSCLC的III期研究在期中分析中达到了无进展生存期的主要研究终点，获得决定性胜出阳性结果。基于此项研究，依达方®单药一线治疗PD-L1表达阳性的晚期NSCLC已提交sNDA，并获优先审评。同时，依达方®联合化疗对比替雷利珠单抗联合化疗一线治疗sq-NSCLC的III期临床研究，由合作伙伴Summit主导开展的依达方®联合化疗联合化疗用于经第三代EGFR-TKI治疗进展的EGFR突变、局晚期或转移性nsq-NSCLC的国际多中心III期临床研究（HARMONi研究）和依达方®联合化疗对比帕博利珠单抗联合化疗一线治疗sq-NSCLC的国际多中心III期研究正在进行中。此外，依沃西新启动3项III期临床研究，包括依沃西联合AK117（CD47）联合方案一线治疗PD-L1阳性头颈鳞癌（vs帕博利珠单抗），依沃西联合方案一线治疗胆道癌（vs度伐利尤单抗联合方案），以及依沃西联合方案一线治疗胰腺癌。总体上，依达方®正通过单药和联合用药在包括肺癌、胰腺癌、乳腺癌、肝细胞癌、结直肠癌等17个适应症领域开展了25+项的临床试验。关于康方生物康方生物（9926.HK）是一家集研究、开发、生产及商业化全球首创或同类最佳创新生物新药于一体的领先企业。自2012年成立以来，公司打造了独有的端对端康方全方位新药研究开发平台（ACE Platform），建立了以Tetrabody双特异性抗体开发技术、抗体偶联（ADC）技术、mRNA技术及细胞治疗技术为核心的研发创新体系，国际化标准的GMP生产体系和运作模式先进的商业化体系，成为了在全球范围内具有竞争力的生物医药创新公司。公司已开发了50个以上用于治疗肿瘤、自身免疫、炎症、代谢疾病等重大疾病的创新候选药物，22个候选药已进入临床（包括11个双抗/多抗/双抗ADC），5个新药已在商业化销售，4个新药5个适应症的上市申请处于审评审批阶段。 2021年8月，公司自主研发的差异化PD-1单抗安尼可®获批上市；2022年6月，公司全球首创的PD-1/CTLA-4双抗开坦尼®获批上市，成为全球首个获批的肿瘤免疫治疗双抗新药，也是中国第一个双特异性抗体新药。2024年上半年，开坦尼®一线治疗晚期宫颈癌的新药上市许可申请（sNDA）已受理，开坦尼®联合方案一线治疗晚期胃癌适应症于同年9月获批上市。2024年5月，公司另一全球首创双抗新药依达方®获得中国国家药品监督管理局批准上市，用于EGFR-TKI治疗进展的局部晚期或转移性nsq-NSCLC，依达方®成为全球首个获批的“肿瘤免疫+抗血管生成”机制双抗新药。同期，依沃西对比帕博利珠单抗一线治疗PD-L1阳性NSCLC获显著阳性结果，同适应症的sNDA获CDE受理，并获优先审评。依沃西成为全球迄今唯一在头对头III期临床研究中证明疗效显著优于“药王”帕博利珠单抗的药物，将有望成为一线肺癌治疗新的标准治疗方案，为患者提供全新更优的“去化疗”选择。此前，2022年12月，公司对外许可了依达方®部分海外权益，并以50亿美金+销售提成的合作方案创下了彼时中国单药对外许可的最高交易金额纪录。2024年9月，公司自主研发的伊喜宁®（伊努西单抗，PCSK9）治疗高胆固醇血症两项适应症获批，成为非肿瘤领域的首个获批产品。康方生物期望通过高效及突破性的研发创新，开发国际首创及同类药物最佳疗法的新药，成为全球领先的生物制药企业。往期推荐产品动态康方生物非肿领域首个新药伊喜宁®（伊努西单抗，PCSK9）治疗高胆固醇血症两项适应症获批上市产品动态一线胃癌全人群获批！康方生物卡度尼利获批第二个适应症数据发布全球首个对比帕博利珠单抗取得显著阳性结果的随机对照大III期研究——依沃西HARMONi-2重磅研究成果在WCLC发表临床进展康方生物卡度尼利联合方案治疗uHCC的III期临床研究完成首例患者入组临床进展康方AK117（CD47）联合方案治疗MDS国际多中心Ⅱ期临床首例患者入组临床进展针对PD-1/L1治疗进展晚期胃癌，卡度尼利+普络西（VEGFR-2）联合疗法Ⅲ期临床完成首例入组产品动态依沃西1L治疗PD-L1阳性NSCLC的sNDA获NMPA受理，肺癌一线将迎“去化疗”新标准方案！数据发布 ASCO Oral & JAMA主刊丨Ⅲ期HARMONi-A研究重磅公布，依沃西疗法有望改变EGFR-TKI进展肺癌全球治疗标准临床进展史无前例！康方依沃西单药对比帕博利珠1L治疗PD-L1阳性NSCLC的III期临床获决定性胜出阳性结果产品动态依达方®首批发货成功！全国晚期肺癌患者迎来全球最新解决方案产品动态康方生物双抗卡度尼利一线治疗晚期宫颈癌全人群的sNDA获CDE受理企业运营康方生物上海全球研发中心启动建设创新全球化战略再提速产品动态首个国产新药IL-12/IL-23单抗报产！康方生物依若奇单抗NDA获NMPA受理临床进展国际多中心注册性III期研究HARMONi-3中国启动：依沃西单抗联合化疗对比帕博利珠单抗联合化疗1L治疗sq-NSCLC 临床进展依沃西联合化疗对比替雷利珠联合化疗一线治疗sq-NSCLC III期临床试验完成首例给药产品动态高达50亿美金！康方生物与Summit就PD-1/VEGF双抗依沃西达成合作和许可协议产品动态全球首个肿瘤免疫治疗双抗——开坦尼®（PD-1/CTLA-4双抗，卡度尼利）获批上市

临床3期免疫疗法CSCO会议临床2期上市后研究

2024-10-30

·PRNewswire

Spyre Therapeutics to Participate in Upcoming November Investor Conferences

WALTHAM, Mass., Oct. 30, 2024 /PRNewswire/ -- Spyre Therapeutics, Inc. (NASDAQ: SYRE), a clinical-stage biotechnology company utilizing best-in-class antibody engineering, rational therapeutic combinations, and precision medicine approaches to target improved efficacy and convenience in the treatment of Inflammatory Bowel Disease ("IBD"), today announced that management will participate in the following upcoming investor conferences: Event: Guggenheim's Inaugural Healthcare Innovation Conference Date: Wednesday, November 13, 2024 Time: 2:30pm ET Event: Stifel 2024 Healthcare Conference Date: Monday, November 18, 2024 Time: 1:15 pm ET Event: Jefferies London Healthcare Conference Date: Wednesday, November 20, 2024 Time: 10:30 am GMT Live audio webcasts and replays of these events will be available on the Spyre investor events website at . About Spyre Therapeutics Spyre Therapeutics is a clinical-stage biotechnology company that aims to create next-generation inflammatory bowel disease (IBD) products by combining best-in-class antibody engineering, rational therapeutic combinations, and precision medicine approaches. Spyre's pipeline includes extended half-life antibodies targeting α4β7, TL1A, and IL-23. For more information, visit Spyre's website at . Follow Spyre Therapeutics on social media: @spyretx and LinkedIn SOURCE Spyre Therapeutics, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED