Long-Term Extension Study (AtDvance) to Evaluate the Safety and Efficacy of GSK1070806 in Participants With Moderate to Severe Atopic Dermatitis. - AtDvance

开始日期2024-07-23

申办/合作机构-

NCT06447506

/ Terminated临床2期

Long-Term Extension Study (AtDvance) to Evaluate the Safety and Efficacy of GSK1070806 in Participants With Moderate to Severe Atopic Dermatitis.

The study is designed to evaluate the long-term safety and efficacy of GSK1070806 in participants with moderate-to severe atopic dermatitis, who have completed phase 2b parent GSK atopic dermatitis (AtD) study (NCT05999799).

开始日期2024-06-05

申办/合作机构

GSK Plc

JPRN-jRCT2071230084

/ Not yet recruiting临床2期IIT

A Phase 2b, Randomized, Double-Blind, Parallel Group, Placebo Controlled, Dose Finding study to evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of GSK1070806 SC injection in Adult Participants with Moderate to Severe Atopic Dermatitis

开始日期2023-12-26

申办/合作机构-

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项与 Aletekitug 相关的文献（医药）

2014-10-01·International journal of clinical pharmacology and therapeutics4区 · 医学

Safety, tolerability, pharmacokinetics, and pharmacodynamics of single-dose antiinterleukin- 18 mAb GSK1070806 in healthy and obese subjects

4区 · 医学

Article

作者: Reid, Juliet ; Abberley, Lee ; Taylor, Adam ; Mistry, Prafull ; DeWal, Stephen ; Pouliquen, Isabelle ; del Cura, Marian Rocha ; McHugh, Simon ; Tong, Xin ; McKie, Elizabeth

OBJECTIVE:

To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of GSK1070806, a novel IgG1 mAb that neutralizes human interleukin (IL)-18.

METHODS:

In this first-timein-human (FTIH) study, cohorts of healthy and obese subjects were randomly allocated to receive single doses of GSK1070806 (0.008 - 10 mg/kg) or placebo. Blood was sampled ≤ 274 days post-dosing, and safety monitored.

RESULTS:

GSK1070806 was generally well tolerated. The most common AEs were nasopharyngitis and headache, arising as frequently in the placebo as in the active drug groups; most AEs were mild to moderate and unrelated to dose level. There were no allergic, delayed-type hypersensitivity, or infusion-related reactions and the incidence of immunogenicity was low. GSK1070806 plasma pharmacokinetic profiles were comparable in healthy and obese subjects; there was no major deviation from dose proportionality for AUC(∞) and C(max) although a trend for dose-dependent increase in t(1/2) was observed. Serum drug-bound IL-18 levels increased post-dosing and were sustained for a long time-period following GSK1070806 administration. Ex-vivo whole blood assay demonstrated prolonged pharmacological activity of GSK1070806 as determined by its primary immunological mechanism of action, inhibition of IL-18-induced IFN-γ production.

CONCLUSION:

GSK1070806 warrants clinical investigation in patients.

PloS one3区 · 综合性期刊

A pilot study evaluating GSK1070806 inhibition of interleukin-18 in renal transplant delayed graft function

3区 · 综合性期刊

ArticleOA

作者: Busz, M ; Harrison, E M ; Abberley, L ; Wlodek, E ; Clatworthy, M ; Devey, L ; Kirkpatrick, R B ; Schroyer, R ; Andrews, S ; Weber, A ; Sheerin, N S ; DeWall, S ; Kingsmore, D ; Krull, D ; Bestard, O ; Stirnadel-Farrant, H A ; Birchler, M ; Wigmore, S J ; Stevenson, K ; Watson, C J E ; Thorneloe, K S ; Noble, R ; Scott, J

Introduction:

Delayed graft function (DGF) following renal transplantation is a manifestation of acute kidney injury (AKI) leading to poor long-term outcome. Current treatments have limited effectiveness in preventing DGF. Interleukin-18 (IL18), a biomarker of AKI, induces interferon-γ expression and immune activation. GSK1070806, an anti-IL18 monoclonal antibody, neutralizes activated (mature) IL18 released from damaged cells following inflammasome activation. This phase IIa, single-arm trial assessed the effect of a single dose of GSK1070806 on DGF occurrence post donation after circulatory death (DCD) kidney transplantation.

Methods:

The 3 mg/kg intravenous dose was selected based on prior studies and physiologically based pharmacokinetic (PBPK) modeling, indicating the high likelihood of a rapid and high level of IL18 target engagement when administered prior to kidney allograft reperfusion. Utilization of a Bayesian sequential design with a background standard-of-care DGF rate of 50% based on literature, and confirmed via extensive registry data analyses, enabled a statistical efficacy assessment with a minimal sample size. The primary endpoint was DGF frequency, defined as dialysis requirement ≤7 days post transplantation (except for hyperkalemia). Secondary endpoints included safety, pharmacokinetics and pharmacodynamic biomarkers.

Results:

GSK1070806 administration was associated with IL18-GSK1070806 complex detection and increased total serum IL18 levels due to IL18 half-life prolongation induced by GSK1070806 binding. Interferon-γ−induced chemokine levels declined or remained unchanged in most patients. Although the study was concluded prior to the Bayesian-defined stopping point, 4/7 enrolled patients (57%) had DGF, exceeding the 50% standard-of-care rate, and an additional two patients, although not reaching the protocol-defined DGF definition, demonstrated poor graft function. Six of seven patients experienced serious adverse events (SAEs), including two treatment-related SAEs.

Conclusion:

Overall, using a Bayesian design and extensive PBPK dose modeling with only a small sample size, it was deemed unlikely that GSK1070806 would be efficacious in preventing DGF in the enrolled DCD transplant population.

Trial registration:

NCT02723786.

Journal of Clinical Medicine

Very Early-Onset IBD-Associated IL-18opathy Treated with an Anti-IL-18 Antibody

Article

作者: Lopez-Castejon, Gloria ; Wynn, Robert F. ; Guha, Anthea ; Hughes, Stephen M. ; Diaz-Pino, Rodrigo ; Arkwright, Peter D. ; Fagbemi, Andrew

Background/Objectives: The aetiology of inflammatory bowel disease (IBD), particularly if occurring early in childhood, is a diverse and patient-focused treatment that is required when standard therapy is ineffective. Materials and Methods: A clinical case report is presented of a child with very early-onset IBD (VEOIBD) and evidence of high serum IL-18 responding to anti-IL-18 immunotherapy. Detailed cytokine profiling was performed by ELISA and multiplex assay flow cytometry. Results: A four-year-old girl with recalcitrant VEOIBD from six weeks old due to an IL-18opathy, characterised by high blood IL-18 concentration, responded to therapy with a novel neutralising anti-IL-18 antibody (GSK1070806). After two years of hospitalisation, the child’s systemic inflammation and extensive upper and lower gastrointestinal mucosal ulceration remitted with this cytokine inhibitor, allowing the discontinuation of total parenteral nutrition and the resumption of normal oral intake and daily activities. After 18 months on regular GSK1070806, the patient remains in disease remission. Conclusions: VEOIBD can be associated with evidence of an underlying IL18opathy and responds to anti-IL-18 antibody therapy. IL-18 should be measured in patients with IBD unresponsive to conventional treatments, and, if elevated, anti-IL-18 antibody therapy should be considered as a potential therapy.

项与 Aletekitug 相关的新闻（医药）

2025-11-14

·发发生信

IF15.7！恭喜山大齐鲁医院！创新运用"MR+药靶筛选"，0实验喜提中科院一区''豪门水刊''！

孟德尔×机器学习: 从遗传视角洞见IBD病因! 看了这篇刚发的《Nature Communications》（双一区TOP）蛋白组学论文，小编直呼内行😊！孟德尔随机化（MR）现在真被玩出花👇！不仅能整合机器学习、多组学数据进行深度挖掘，还能联动临床表型、药物靶点多个数据库。更厉害的是，人家把“观测-推断-定位”这套流程全部打通， ✔从近3000个血浆蛋白里捞出关键靶点， ✔用MR+共定位锁死因果证据，最终通过单细胞技术精准“揪出”结肠黏膜里的那群“捣蛋鬼”✨。如果你也想利用孟德尔随机化进行生信分析，快关注发发生信，你的下一篇顶刊论文，或许就从这里开始！分析框架 📌六大维度的研究分析框架已整理，点击图片查看（5-10分钟获取核心要点）。 1.分析维度 | 2.关键发现 | 3.代表性数据 4.科学意义 | 5.可视化面板 | 6.研究亮点利用孟德尔随机化发文真的不难，你还在观望什么？【发发生信】定制思路，全面数据分析，下一篇高分SCI就是你！文献解读标题：一项前瞻性队列研究和遗传分析中2923种血浆蛋白与新发炎症性肠病的关联发表期刊：Nature Communications 发表时间：2025年3月21日影响因子：15.7/Q1 科学验证因果，方法决定高度。完整孟德尔随机化方案，助力您的研究登上更高学术舞台。研究背景炎症性肠病（IBD）的全球发病率不断上升，但其分子机制尚不明确，目前治疗手段效果有限，亟需通过大规模蛋白质组学与遗传学方法探索其致病机制与潜在治疗靶点。研究方法本研究基于英国生物银行（UKB）前瞻性队列，结合2923种血浆蛋白的观测性分析与孟德尔随机化（MR）、共定位分析，系统评估了蛋白质与IBD及其亚型之间的因果关系。研究结果解析 01 研究概览：为了系统性地揭示血浆蛋白质与炎症性肠病（IBD）之间的复杂关系，研究者设计了一个多阶段的研究流程【图1】。图1.研究设计示意图该设计首先在一个大规模前瞻性队列中识别与IBD发病相关的蛋白质，进而利用遗传学方法验证其因果作用，最后通过多组学数据深入探索其生物学机制和临床转化潜力。这一循序渐进的策略，旨在确保研究发现具有稳健性与深度。 02 观察性分析与预测模型：初步分析显示，在调整多种混杂因素后，仍有673种血浆蛋白与未来的IBD风险显著相关【图2c】，其中295种与克罗恩病（CD）相关【图2f】，125种与溃疡性结肠炎（UC）相关【图2i】。这一发现揭示了IBD发病前存在的广泛分子紊乱。图2.英国生物样本库中单个蛋白质与炎症性肠病及其亚型的火山图分析然而，一个核心问题随之产生：这些蛋白水平的改变，究竟是驱动疾病发生的“因”，还是疾病在亚临床阶段已开始活动的“果”？观察性研究难以区分这两者。为了验证这些蛋白的预测价值，研究者构建了预测模型，发现结合蛋白质信息与传统风险因素的模型，其预测效能（AUC=0.68）显著优于传统模型（AUC=0.62）。这证明蛋白质在早期预警中潜力巨大，但要将其确立为干预靶点，必须确认其因果地位。 03 遗传证据与靶点优先序：为了突破观察性研究的局限，研究者引入了孟德尔随机化（MR）分析【图1，阶段3】。这种方法利用与蛋白质水平相关的遗传变异作为工具变量，能有效规避传统混杂和反向因果。MR分析结果【图3a-c】将候选蛋白的范围从数百个显著缩小至18个与IBD、6个与CD、4个与UC存在潜在因果关系的蛋白。图3.针对候选蛋白质与炎症性肠病及其亚型的观察性分析和孟德尔随机化（MR）分析然而，MR分析的一个潜在陷阱是：蛋白质与疾病的遗传信号可能仅仅因为在基因组位置上相邻而巧合地相关。为此，研究者进行了贝叶斯共定位分析，以确认两者是否由同一个因果遗传变异驱动。基于此，研究者最终将22个候选蛋白分为两个等级： Tier 1（8个核心靶点）：包括IL12B, CD6, MXRA8, CXCL9, IFNG, CCN3, RSPO3, IL18。它们不仅通过MR检验，更拥有强大的共定位证据，是干预靶点中的“高置信度”候选。 Tier 2（14个潜在靶点）：包括CCL20, TNFRSF9等。它们通过了观察性和MR检验，但共定位证据较弱，作为重要的补充靶点库。 04 细胞定位与分子网络：锁定候选蛋白后，研究者深入探究其作用的细胞场所与生物学功能【图1，阶段4】。通过分析结肠黏膜的单细胞RNA测序数据【图4】，研究者发现诸如CCL20（富集于巨噬细胞和T细胞）、CD6（T细胞）、CXCL9（巨噬细胞）和IL18（上皮细胞）等关键蛋白，在IBD患者的相应细胞中表达显著上调。为这些血浆中的“嫌疑犯”找到了其在犯罪现场（肠道炎症局部）的具体“岗位”，极大地增强了它们参与IBD发病的可信度。图4.候选蛋白编码基因在结肠黏膜中的单细胞表达图谱进一步的蛋白互作（PPI）与通路富集分析显示，这些候选蛋白并非孤立作战，而是构成了一个紧密协作的分子网络，共同参与炎症反应、免疫调节及JAK-STAT、趋化因子等信号通路。这描绘了一幅清晰的图景：IBD的发生是由一个复杂的多蛋白、多通路网络共同驱动的。 05 成药性评估与转化前景：最终，所有这些发现的价值都将落脚于临床转化。研究者对这些候选靶点进行了系统的成药性评估【表1】，结果令人振奋：表1.与IBD及其亚型相关的候选蛋白研究结果总结已有临床基础：Tier 1蛋白中的IL12B、IFNG和IL18，已有靶向药物（如乌司奴单抗、奥沙拉嗪、GSK1070806）被批准或正处于IBD的临床试验中，这从临床层面反向验证了本发现的可靠性。全新靶点与老药新用：本研究新发现的CD6、MXRA8、CXCL9、CCN3和RSPO3这五个核心靶点，为药物研发开辟了新方向。尤其值得注意的是，靶向CD6的伊塔利珠单抗已用于治疗银屑病，其重新用于IBD治疗具有巨大的潜力，可显著缩短研发周期。研究确定了22个与IBD风险相关的蛋白质，其中IL12B、CD6、MXRA8等8个蛋白被列为一级候选靶点（Tier 1），为IBD的精准治疗和药物重定位提供了新方向。想学习如何复刻这类高分研究的同学，欢迎联系发发生信！ End 发发生信选题设计丨数据分析丨思路建议从零突破到SCI发表往期推荐 1 IF 15.7！清华大学本科生一作，用机器学习0实验轻松登顶Nature子刊！思路简单可复现！ 2 IF 42.5！恭喜复旦大学郁金泰团队, 登顶Cell ! "机器学习+孟德尔"思路直接惊艳审稿人！ 3 IF10.6！我愿称之为一区"水刊"的神，接收到见刊仅需4天！这效率简直离谱！求点赞求分享求喜欢

信使RNA

2025-10-01

·BioDialectics

特应性皮炎的多面驱动因子—IL-18

特应性皮炎（AD）作为一种常见的慢性炎症性皮肤病，以剧烈瘙痒、皮肤屏障功能障碍及免疫细胞浸润为核心特征，其发病机制复杂且尚未完全阐明。近期发表的文章《IL-18 in atopic dermatitis-A multifaceted driver of skin inflammation》，系统揭示白细胞介素-18（IL-18）在AD病理生理过程中的关键作用，为理解AD炎症调控机制及开发新型治疗策略提供了重要理论依据。一、IL-18的生物学特性：激活、调控与功能多样性 IL-18作为IL-1细胞因子家族成员，其生物学活性的发挥依赖精准的激活调控与信号传导，且功能具有显著的组织和语境依赖性。 1.产生与激活：多途径调控的“炎症开关” 1）细胞来源与储备：生理状态下，IL-18以无活性前体（pro-IL-18）形式组成表达于上皮细胞（尤其是皮肤基底及棘层角质形成细胞）、巨噬细胞、树突状细胞（DCs）等，皮肤是其最主要的储备组织；炎症刺激（如病原体入侵、组织损伤）可进一步诱导其表达上调。 2）pro-IL-18的激活途径需经蛋白酶切割方可激活，主要途径包括：经典焦亡途径：模式识别受体（PRR）激活后组装炎症小体（如NLRP1、NLRP3、AIM2等），激活胱天蛋白酶-1（caspase-1），切割pro-IL-18生成成熟IL-18，同时释放的N端GasderminD（N-GSDMD）形成膜孔，介导IL-18选择性释放；非经典途径：胞内脂多糖（LPS）直接激活人caspase-4/5，不依赖炎症小体即可切割pro-IL-18；其他途径：Fas诱导的caspase-8激活、细菌蛋白酶（如链球菌致热外毒素B）、NK细胞/CD8⁺T细胞衍生颗粒酶等，也可在炎症小体非依赖模式下激活pro-IL-18。 2.信号传导与调控：精准平衡的“分子网络” 1）受体与信号通路：成熟IL-18需与异二聚体受体（IL-18Rα/IL-18RAP）结合，通过招募MyD88、TRAM等适配器分子，激活IRAK1/4-TRAF6信号轴，进而调控NF-κB、AP-1等转录因子，同时激活MAPK（ERK、JNK）、PI3K/Akt及STAT3通路，参与炎症反应、细胞存活及应激应答。 2）内源性抑制机制：IL-18活性受双重调控以维持免疫稳态： IL-18结合蛋白（IL-18BP）：作为可溶性诱饵受体，与IL-18高亲和力结合使其失活，血清中IL-18BP浓度远超IL-18，约95%循环IL-18处于结合抑制状态，且IL-18诱导的IFN-γ可反向上调IL-18BP，形成负反馈； IL-37：通过竞争结合IL-18Rα并招募IL-1R8/SIGIRR，阻断IL-18信号传导，同时触发抗炎反应，其表达可由LPS、TNF-α等炎症刺激诱导。 3.功能多样性：语境依赖的“炎症调节器” IL-18的功能并非固定不变，而是受组织微环境、协同细胞因子及细胞类型影响： 1）经典功能：传统认知中，IL-18主要促进NK细胞、Th1细胞分泌IFN-γ，参与Th1型免疫应答； 2）AD中的特殊作用：在AD等过敏性疾病中，IL-18可转向促进Th2型炎症，通过激活致病性Th2（pTh2）细胞、2型固有淋巴细胞（ILC2）等，诱导IL-4、IL-5、IL-13等Th2细胞因子分泌； 3) 组织特异性：在胃肠道中，IL-18支持黏膜免疫与屏障完整性，而在皮肤中则主要加剧allergic炎症，这种差异反映了其功能的语境依赖性。二、IL-18在AD中的作用机制：从屏障破坏到炎症放大在AD病理过程中，IL-18通过多维度调控，贯穿“屏障损伤-炎症激活-炎症放大”的全链条，成为连接皮肤屏障功能障碍与免疫紊乱的关键分子。 1.破坏皮肤屏障：形成“恶性循环” 直接抑制屏障相关蛋白：体外实验证实，IL-18可下调角质形成细胞中丝聚蛋白（FLG）、兜甲蛋白（LOR）的表达，这两种蛋白是皮肤角质层的核心结构成分，其表达降低直接导致经表皮水分流失（TEWL）增加、天然保湿因子（NMF）减少，加剧屏障功能障碍；反向促进自身释放：FLG或LOR敲低的角质形成细胞会进一步增加IL-18分泌，形成“IL-18破坏屏障→屏障受损促进IL-18释放”的恶性循环。临床研究显示，AD患者（尤其是携带FLG突变者）皮肤角质层IL-18水平显著升高，且与TEWL呈正相关，印证了这一机制的临床相关性。 2.驱动微生物相关炎症：链接菌群失调与免疫激活 AD皮肤常伴随金黄色葡萄球菌（S.aureus）定植增加，而IL-18是介导微生物刺激与炎症反应的关键桥梁： S.aureus的直接诱导：S.aureus的毒力因子（如肠毒素B、蛋白A）可激活角质形成细胞NLRP1炎症小体，促进caspase-1依赖的IL-18释放；同时，S.aureus感染还可激活巨噬细胞炎症小体，进一步放大IL-18介导的炎症；共生菌的间接影响：皮肤共生菌表皮葡萄球菌分泌的酚溶性调节蛋白，也可触发角质形成细胞caspase-1激活与IL-18释放，且FLG缺陷会增强这一响应，提示IL-18可能是结构屏障缺陷与菌群紊乱交互作用的“分子枢纽”。 3.调控免疫细胞：放大Th2型炎症 IL-18通过靶向多种免疫细胞，精准放大AD中的Th2型炎症反应，其作用具有细胞特异性：致病性Th2（pTh2）细胞：pTh2细胞是AD中Th2炎症的核心效应细胞，与常规Th2细胞不同，其持续表达IL-18受体（IL-18R），IL-18可显著增强其IL-13、IL-22分泌；且IL-9可进一步上调pTh2细胞IL-18R表达，形成“IL-9-IL-18-pTh2”的正向放大环路； 2型固有淋巴细胞（ILC2）：皮肤ILC2高表达IL-18R，IL-18可直接激活其分泌IL-5、IL-13，且与IL-3协同作用时激活效应更强；IL-18敲除小鼠的AD模型中，ILC2浸润与细胞因子分泌显著减少，证实其对ILC2的调控作用； NK细胞：AD患者存在NK细胞数量减少、细胞毒性受损的现象，IL-18通过激活诱导细胞死亡（AICD）、NK细胞fratricide（自相残杀）及TNF-α介导的细胞死亡，导致NK细胞耗竭；同时，IL-18还可使NK细胞从分泌IFN-γ转向分泌TNF-α，削弱其抑制Th2炎症的能力，进一步加剧免疫失衡。三、IL-18与AD的临床关联：从生物标志物到治疗靶点 IL-18不仅是AD病理机制中的关键分子，还具有重要的临床转化价值，可作为AD的生物标志物及潜在治疗靶点。 1.AD生物标志物：评估病情与治疗响应诊断与严重度评估：AD患者血清及皮肤IL-18水平均显著升高，且与疾病严重度评分（EASI/SCORAD）呈中等程度正相关（r≈0.35-0.60），其相关性优于胸腺基质淋巴细胞生成素（TSLP）。预测与监测价值：非病变皮肤IL-18升高可在AD临床症状出现前预测疾病发生，提示其潜在的早期诊断价值；此外，皮肤IL-18水平可随局部治疗（如外用药物）正常化，血清IL-18则对系统性治疗（如度普利尤单抗）响应敏感，可用于监测治疗效果；亚型区分：IL-18在外源性AD（高IgE、Th2主导）中水平显著高于内源性AD（正常IgE、Th1/Th17主导），为AD亚型分型提供了分子依据。 2.治疗靶点：新型干预策略的开发基于IL-18在AD中的核心作用，多种靶向IL-18的治疗策略已进入临床开发阶段，主要包括：抗IL-18抗体：AVTX007（IIa期）、GSK1070806（IIb期）、CMK389（II期已完成）等药物均显示出良好的短期安全性，且GSK1070806在早期临床试验中呈现剂量依赖性的EASI评分改善及瘙痒缓解，提示其临床潜力。重组IL-18BP：IL-18BP作为内源性抑制剂，已在巨噬细胞活化综合征等疾病中验证疗效，其白蛋白结合修饰形式可延长半衰期，在小鼠AD模型中，该修饰形式的抗炎效果优于抗IL-18单克隆抗体。上游炎症小体/焦亡抑制剂：抑制炎症小体组装（如NLRP1抑制剂）或焦亡关键分子（如GSDMD抑制剂），可减少IL-18激活释放，小鼠模型显示此类干预可缓解AD样皮炎。四、总结思考：治疗机遇与挑战 IL-18作为AD炎症的多面驱动因子，其研究为AD病理机制解析及治疗突破提供了重要视角，但从基础研究到临床应用仍需解决多重关键问题。 1.安全性平衡：规避长期抑制的潜在风险 IL-18在正常免疫防御（如抗菌、抗肿瘤）中具有重要作用，长期抑制可能带来免疫功能受损风险：短期安全性验证：目前临床研究显示抗IL-18药物短期安全性良好，但需长期随访评估其对感染（如皮肤细菌/病毒感染）、肿瘤发生的影响；局部治疗优先：鉴于皮肤是IL-18的主要作用部位，开发局部IL-18抑制剂（如外用IL-18BP、局部炎症小体抑制剂）可能在增强疗效的同时降低全身毒性。 3.联合治疗：协同改善AD多维度病理 AD的复杂性决定了单一靶点治疗难以完全控制疾病，联合治疗具有广阔潜力：与Th2细胞因子抑制剂联用：IL-18主要作用于pTh2细胞上游激活环节，与IL-4/IL-13抑制剂（如度普利尤单抗）联用，可从“上游激活-下游效应”双重阻断Th2炎症，增强疗效；与JAK抑制剂联用：JAK抑制剂可抑制IL-18下游信号通路（如STAT3、NF-κB），与IL-18抑制剂联用可能产生协同抗炎效应，同时覆盖AD中的多种炎症通路；与屏障修复剂联用：针对IL-18介导的屏障破坏，联合使用皮肤屏障修复剂（如神经酰胺、胆固醇），可打破“屏障受损-IL-18释放”的恶性循环，提升长期治疗效果。 IL-18作为AD病理中的关键分子，IL-18靶向疗法有望成为AD治疗的重要补充，为更多难治性AD患者带来新的治疗选择。但同时也需认识到，AD的异质性及IL-18功能的复杂性仍需进一步研究，只有通过多学科协作、基础与临床转化结合，才能真正实现IL-18靶向治疗的临床价值。《IL-18 in atopic dermatitis - A multifaceted driver of skin inflammation》，The Journal of Allergy and Clinical Immunology，2025

临床结果

2025-04-30

·EndPoints

GSK's supply chain 'reset' after Haleon spinoff to ease tariff impact, CEO says

GSK said its decoupling with Haleon is a key reason why it views itself as “well-positioned” in the face of potential pharma-specific tariffs. When the drugmaker went through its “ demerger ” with the consumer health business in 2022, there were “very intentional, deliberate choices to reset” its supply chain for “regional resilience” as well as “double sourcing” to allow for flexibility, CEO Emma Walmsley said. It has “mitigation options” that it could execute across its manufacturing networks once pharma levies are in place, the UK company said in a statement. “We’re watching it very carefully … we are well-prepared,” Walmsley said during GSK’s first-quarter earnings call with the media. Some drug developers and CDMOs have similarly expressed how their earlier moves — which were made even before the talk of tariffs emerged — would help them navigate sector-specific levies regardless of what these might look like. President Donald Trump’s tariffs have been a central theme during this earnings season as drugmakers disclose their exposures and strategies to varying degrees. Last week, Roche CEO Thomas Schinecker said the pharma tariffs could have a negative impact on dealmaking. But Walmsley somewhat disagreed, saying “there are some opportunities” for deals and that half of GSK’s pipeline comes from this business development approach. “We’re constantly looking at things … and we also continue to look at the opportunities out of China on BD. We’ve done several good deals ,” she said. GSK’s disappointing vaccine sales stood out in Q1. Sales for this franchise dropped 6% in the quarter due to “known headwinds,” GSK said. Shingrix struggled in the US due to “harder-to-reach unvaccinated customers” and increased channel inventory consumption. As for Arexvy, sales disappointed because of the FDA’s Advisory Committee on Immunization Practices’ constricted recommendation only for people aged 60 to 74. But Jefferies analysts said GSK’s vaccine sales of £2.1 billion were actually better than consensus expectations of £2.05 billion. Shingrix beat forecasts with £867 million in worldwide sales, although Arexvy sales are still notably low at £78 million. Walmsley added that both vaccines still have room for growth internationally. Despite these market challenges, Walmsley told the media GSK does not intend to change its R&D plans for vaccines. Overall, GSK had a positive total sales profile, pulling in £7.5 billion in Q1, up 4% at constant exchange rates. Its shares were up by as much as 4% on the London Stock Exchange on Wednesday morning. The company’s specialty medicines portfolio had a particularly solid performance at £2.9 billion — a 17% jump — beating Jefferies’ consensus estimates of £2.84 billion. “We’ve been able to strengthen the portfolio with a shift to more specialty medicines, and that creates oxygen through the gross margin,” Walmsley said. Notably, Jemperli pulled in £174 million in Q1 compared with a lower benchmark of £145 million. GSK said Jemperli’s US sales momentum is supported by the drug’s approval in all patients with primary advanced or recurrent endometrial cancer. GSK also touted its market progress with Ojjaara at £112 million, as the myelofibrosis therapy makes headway in the US and other territories. But analysts noted the drug’s sales just missed forecasts at £117 million. Nonetheless, GSK’s overall showing on Wednesday follows the optimistic tune played in February, when it set a higher bar for its 2031 sales outlook to at least $40 billion. This is a £2 billion jump from a prior target. Looking at its clinical pipeline, GSK discontinued a Phase 2 trial of an anti-IL18 antibody, codenamed GSK1070806, for atopic dermatitis due to pipeline prioritization. Endpoints News previously reported that GSK’s ViiV Healthcare stopped work on its HIV antiviral named VH3739937.

上市批准疫苗临床2期临床结果

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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
中度特应性皮炎	临床2期	美国	GSK Plc	2023-11-16
中度特应性皮炎	临床2期	中国	GSK Plc	2023-11-16
中度特应性皮炎	临床2期	日本	GSK Plc	2023-11-16
中度特应性皮炎	临床2期	阿根廷	GSK Plc	2023-11-16
中度特应性皮炎	临床2期	保加利亚	GSK Plc	2023-11-16
中度特应性皮炎	临床2期	加拿大	GSK Plc	2023-11-16
中度特应性皮炎	临床2期	捷克	GSK Plc	2023-11-16
中度特应性皮炎	临床2期	法国	GSK Plc	2023-11-16
中度特应性皮炎	临床2期	德国	GSK Plc	2023-11-16
中度特应性皮炎	临床2期	希腊	GSK Plc	2023-11-16

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临床结果

适应症

分期

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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


NCT04975438 (CTgov)	临床1期	中度特应性皮炎 \| 重度特应性皮炎	34	GSK1070806 (Group 1: GSK1070806)	窪襯顧鏇繭膚膚獵憲艱(築簾繭簾夢鑰蓋餘築鏇) = 獵鏇艱繭壓網醖壓鹹夢醖願繭蓋範廠積製遞選 (顧衊鑰簾鑰淵繭膚範構, 築窪鹹夢窪觸醖構壓網 ~ 鹹選繭鹽簾膚獵觸鹹廠) 更多	-	2024-07-23
NCT04975438 (CTgov)	临床1期	中度特应性皮炎 \| 重度特应性皮炎	34	Placebo (Group 1: Placebo)	窪襯顧鏇繭膚膚獵憲艱(築簾繭簾夢鑰蓋餘築鏇) = 廠壓廠築獵艱簾獵範淵醖願繭蓋範廠積製遞選 (顧衊鑰簾鑰淵繭膚範構, 衊廠獵夢衊憲繭積鑰積 ~ 艱蓋願窪齋齋願壓築餘) 更多	-	2024-07-23
GSK1070806 (EADV2023)	临床1期	-	-	GSK1070806	遞糧夢鑰鹽範齋鹹網鹽(淵獵鹽餘蓋糧夢襯餘艱) = 齋膚餘壓鹹獵醖壓鹹衊積願簾餘衊鏇觸艱獵糧 (襯窪鏇製夢積衊觸願糧 )	积极	2023-10-11
NCT02723786 (Pubmed \| J Biol Chem \| PLoS One) 人工标引	临床2期	移植物功能延迟恢复	7	GSK1070806	艱製獵範獵構膚鑰醖餘(壓獵鏇顧廠壓獵齋衊築) = 齋窪鬱簾衊鬱鏇願築顧製廠繭廠顧膚膚襯齋襯 (鹹遞糧襯遞膚鏇壓觸餘 ) 更多	不佳	2021-03-08
NCT02723786 (CTgov)	临床2期	肾移植排斥反应 \| 移植物功能延迟恢复	7	GSK1070806+basiliximab+tacrolimus+azathioprine+mycophenolate mofetil	顧廠壓鹽壓網齋簾糧廠 = 範醖壓顧廠齋範壓淵選鬱獵襯蓋遞積齋膚淵糧 (壓醖顧範壓遞鬱鏇構鏇, 夢築願築築鹹糧憲簾鑰 ~ 簾窪顧餘憲襯選簾襯淵) 更多	-	2019-06-10