Phase 1, Open Label, Single Dose Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics of Enpatoran in Male and Female Participants

The purpose of this study is to assess the effect of renal impairment on the pharmacokinetics of enpatoran.

开始日期2024-09-24

申办/合作机构

Merck Healthcare KGaA

[+1]

NCT06589726

/ Completed临床1期

A Single-Dose, Randomized, Double-Blind, Placebo- and Positive-Controlled, 4-Way Crossover Study to Evaluate the Effect of Enpatoran on the QTc (Corrected QT) Interval in Healthy Adult Participants

The purpose of this study is to assess potential effects of enpatoran on cardiac repolarization (i.e. prolongation of QT interval).

开始日期2024-09-10

申办/合作机构

Merck Healthcare KGaA

[+1]

NCT05650567

/ Recruiting临床2期

A Phase IIa, Randomized, Parallel, Double-Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Enpatoran in Dermatomyositis and Polymyositis Participants Receiving Standard of Care (NEPTUNIA)

The purpose of this study is to evaluate the efficacy and safety of orally administered M5049 in idiopathic inflammatory myopathies, specifically dermatomyositis (DM) and polymyositis (PM) participants for 24 weeks.

开始日期2023-01-19

申办/合作机构

EMD Serono Research & Development Institute, Inc.

[+1]

100 项与 Enpatoran 相关的临床结果

登录后查看更多信息

100 项与 Enpatoran 相关的转化医学

登录后查看更多信息

100 项与 Enpatoran 相关的专利（医药）

登录后查看更多信息

项与 Enpatoran 相关的文献（医药）

2025-05-07·JOURNAL OF LEUKOCYTE BIOLOGY

Toll-like receptor 8 activation induces a neutrophil inflammatory phenotype: therapeutic implications for the utility of toll-like receptor 8 inhibition

Article

作者: Studham, Matthew ; Shaw, Jamie ; Coughlin, Matthew ; Bender, Andrew T ; Schmidt, Angelika ; Catalina, Michelle D ; Przetak, Melinda ; Strand, Fatima ; Kalatskaya, Irina

Abstract:

Excessive activation of toll-like receptor 7 and 8 (TLR7/8) plays a role in the pathogenesis of autoimmune diseases and is associated with negative outcomes from viral infections. Neutrophil activation is highly inflammatory and mediates tissue damage. We explored the effects of TLR7/8 activation in neutrophils to better understand neutrophil biology and evaluate the therapeutic utility of TLR7/8 inhibitors in indications where neutrophils contribute to disease pathogenesis. We found that TLR8, but not TLR7, is active in human neutrophils. TLR8 activation led to increased interleukin-8 (IL-8) secretion and resulted in significant changes in gene expression, as determined by RNA sequencing, with increased expression of genes encoding cytokines and other inflammatory mediators. Type I interferon (IFN) also induced gene expression changes distinct from those induced by TLR8. Additionally, neutrophil extracellular traps (NET) formation and DNA release, or NETosis, was induced by TLR8 activation in IFN-primed neutrophils. Treatment with a TLR7/8 inhibitor (CMPD2) effectively blocked IL-8 secretion and NETosis. In a Phase II clinical trial in COVID-19 pneumonia, TLR7/8 inhibition with enpatoran affected neutrophil counts. Expression of NFKBIZ was induced by TLR8 in neutrophils in vitro and found to also be reduced by enpatoran in patients with COVID-19, suggesting it may be useful as a marker for TLR8-activated neutrophils and for identifying candidate diseases and patients that may benefit from treatment with a TLR7/8 inhibitor. Overall, our findings provide new insights into TLR8 and neutrophil biology that have therapeutic implications in autoimmune diseases and immune-mediated inflammation.

2024-10-01·British Journal of Pharmacology

Factor XII and prekallikrein promote microvascular inflammation and psoriasis in mice

Article

作者: Wang, Miao ; Wan, Qing ; Zhang, Yurong ; Rao, Haojie ; Li, Huihui ; Xu, Pengfei ; Yang, Jianfeng ; Zhang, Yingjie ; Chen, Zengrong ; Guo, Junyan ; Chen, Hong

Background and Purpose:

Psoriasis is an autoimmune inflammatory skin disease, featuring microvascular abnormalities and elevated levels of bradykinin. Contact activation of Factor XII can initiate the plasma kallikrein‐kinin cascade, producing inflammation and angioedema. The role of Factor XII in psoriasis is unknown.

Experimental Approach:

The effects of deficiency of Factor XII or its enzymatic substrate, prekallikrein, were examined in the imiquimod‐induced mouse model of psoriasis. Skin microcirculation was assessed using intravital confocal microscopy and laser Doppler flowmeter. A novel antibody blocking Factor XII activation was evaluated for psoriasis prevention.

Key Results:

Expression of Factor XII was markedly up‐regulated in human and mouse psoriatic skin. Genetic deletion of Factor XII or prekallikrein, attenuated imiquimod‐induced psoriatic lesions in mice. Psoriatic induction increased skin microvascular blood perfusion, causing vasodilation, hyperpermeability and angiogenesis. It also promoted neutrophil‐vascular interaction, inflammatory cytokine release and enhanced Factor XII / prekallikrein enzymatic activity with elevated bradykinin. Factor XII or prekallikrein deficiency ameliorated these microvascular abnormalities and abolished bradykinin increase. Antagonism of bradykinin B2 receptors reproduced the microvascular protection of Factor XII / prekallikrein deficiency, attenuated psoriatic lesions, and prevented protection by Factor XII / prekallikrein deficiency against psoriasis. Furthermore, treatment of mice with Factor XII antibody alleviated experimentally induced psoriasis and suppressed microvascular inflammation.

Conclusion and Implications:

Activation of Factor XII promoted psoriasis via prekallikrein‐dependent formation of bradykinin, which critically mediated psoriatic microvascular inflammation. Inhibition of contact activation represents a novel therapeutic strategy for psoriasis.

2024-10-01·CTS-Clinical and Translational Science

Asia‐inclusive drug development leveraging principles of ICH E5 and E17 guidelines: Case studies illustrating quantitative clinical pharmacology as a foundational enabler

Review

作者: Kuroki, Yoshihiro ; Venkatakrishnan, Karthik ; Bolleddula, Jayaprakasam ; Dong, Jennifer ; Strotmann, Rainer ; Lu, Hong ; Klopp‐Schulze, Lena ; Mukker, Jatinder Kaur ; Gao, Wei ; Terranova, Nadia ; Li, Dandan ; Goteti, Kosalaram

Abstract:

With the International Conference on Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) E17 guidelines in effect from 2018, the design of Asia‐inclusive multiregional clinical trials (MRCTs) has been streamlined, thereby enabling efficient simultaneous global development. Furthermore, with the recent regulatory reforms in China and its drug administration joining the ICH as a full regulatory member, early participation of China in the global clinical development of novel investigational drugs is now feasible. This would also allow for inclusion of the region in the geographic footprint of pivotal MRCTs leveraging principles of the ICH E5 and E17. Herein, we describe recent case examples of model‐informed Asia‐inclusive global clinical development in the EMD Serono portfolio, as applied to the ataxia telangiectasia and Rad3‐related inhibitors, tuvusertib and berzosertib (oncology), the toll‐like receptor 7/8 antagonist, enpatoran (autoimmune diseases), the mesenchymal–epithelial transition factor inhibitor tepotinib (oncology), and the antimetabolite cladribine (neuroimmunological disease). Through these case studies, we illustrate pragmatic approaches to ethnic sensitivity assessments and the application of a model‐informed drug development toolkit including population pharmacokinetic/pharmacodynamic modeling and pharmacometric disease progression modeling and simulation to enable early conduct of Asia‐inclusive MRCTs. These examples demonstrate the value of a Totality of Evidence approach where every patient's data matter for de‐risking ethnic sensitivity to inter‐population variations in drug‐ and disease‐related intrinsic and extrinsic factors, enabling inclusive global development strategies and timely evidence generation for characterizing benefit/risk of the proposed dosage in Asian populations.

项与 Enpatoran 相关的新闻（医药）

2025-05-26

·汇聚南药

红斑狼疮「潜在大药」亮相

红斑狼疮的靶向治疗药物种类丰富，包括生物制剂和小分子药物等，其中生物制药有3款药获批上市，而尚无用于治疗红斑狼疮的小分子靶向药物获批上市。近期，德国默克宣布其潜在用于治疗皮肤型红斑狼疮（CLE）和系统性红斑狼疮（SLE）的“first-in-class”口服小分子TLR7/8抑制剂enpatoran的一项2期WILLOW研究取得积极结果。此次2期临床的成功，使得红斑狼疮的靶向小分子药物研发更进一步。红斑狼疮靶向治疗生物制剂生物制剂是红斑狼疮靶向治疗的重要组成部分，主要通过靶向特定的细胞因子或免疫细胞来调节免疫反应，包括B细胞激活因子（BAFF/BLyS）、增殖诱导配体（APRIL）、CD20、CD22、T细胞相关靶点CTLA4、CD40L和IL6R等（图1）。图1 红斑狼疮靶向治疗常见的靶点图片来源：参考文献1目前已获批用于治疗红斑狼疮的靶向治疗生物制剂有贝利尤单抗、阿尼鲁单抗和泰它西普。1.贝利尤单抗贝利尤单抗是由GSK和Human Genome Sciences（HGS）共同研发的一种靶向BAFF/BLyS的全人源IgG1λ单克隆抗体，于2011年3月首次在美国获批上市，用于治疗活动性、自身抗体阳性的成人系统性红斑狼疮（SLE）患者，是首个专门用于治疗红斑狼疮的生物制剂。随后2019年12月和2023年2月分别获批用于治疗活动性狼疮肾炎（LN）的成人患者和潜在治疗系统性硬化症（SSc）。贝利尤单抗的获批基于多项关键临床试验，包括BLISS-52和BLISS-76试验以及BLISS-LN试验等，其中BLISS-52和BLISS-76试验结果显示，贝利尤单抗联合标准治疗显著提高了患者的SRI-4反应率（图2）。图2 贝利尤单抗的部分临床试验结果图片来源：参考文献2贝利尤单抗自上市以来销售额呈逐年上升趋势，2022年销售额达11.46亿英镑（约14.9亿美元），2022年销售额达13.49亿英镑（约17.54亿美元），2024年销售额约14.90亿英镑（约19.37亿美元），根据Verified Market Reports的数据，贝利尤单抗的销售额预计到2033年将增至32亿美元，年复合增长率为6.9%。2.阿尼鲁单抗阿尼鲁单抗是由阿斯利康研发的靶向Ⅰ型干扰素受体1（IFNAR1）的人单克隆抗体，于2021年8月获得美国FDA批准，用于治疗正在接受标准疗法的中度至重度SLE成年患者。此次获批是基于两项TULIP 3期试验和MUSE 2期试验。在这些试验中，与安慰剂相比，更多接受阿尼鲁单抗治疗的患者经历了包括皮肤和关节在内的器官系统整体疾病活动度的降低，并且口服皮质类固醇（OCS）的使用持续减少。阿尼鲁单抗目前也在中国开展SLE临床III期试验。3.泰它西普泰它西普是由荣昌生物自主研发的靶向BAFF/BlyS和APRIL两种关键的B细胞存活因子的新型融合蛋白，于2021年3月在中国获得有条件批准，用于治疗活动性SLE患者，有研究显示抗磷脂抗体阳性SLE患者中显示有效，有望进一步拓宽其适应人群。2024年7月，NMPA接受了泰它西普用于治疗类风湿关节炎（RA）的新临床适应症申请，除此之外，泰它西普还在开展重症肌无力（MG）、IgA肾病和原发性干燥综合征（pSS）等适应症。2025年4月8日，荣昌生物在2025年美国神经病学学会（AAN）年会上公布了3期评估泰它西普在全身性重症肌无力（gMG）患者中的疗效和安全性临床试验（NCT05737160）的结果。研究结果显示：在泰它西普240 mg组的参与者中，98.1%的患者在第24周时体重肌无力日常生活活动（MG-ADL）评分降低≥3分，87%的患者定量重症肌无力（QMG）评分降低≥5分。在迄今为止报道的3期研究中，泰利西普在所有gMG药物中具有最高的MG-ADL反应率，它将提供一种重要的新治疗选择gMG。除了上市获批的用于治疗红斑狼疮的生物制剂外，还有很多在研的生物制剂，包括奥滨尤妥珠单抗、达匹罗珠单抗和利替非利单抗等。1.奥滨尤妥珠单抗奥滨尤妥珠单抗是由罗氏研发的是一种II型抗CD20单克隆抗体，于2016年2月首次在FDA获批上市，用于治疗复发或难治性滤泡性淋巴瘤（FL），除此之外，奥滨尤妥珠单抗在治疗狼疮性肾炎和系统性红斑狼疮方面显示出显著的临床益处，特别是在对传统治疗耐药的患者中。FDA已同意审查罗氏提交的奥滨尤妥珠单抗用于治疗狼疮性肾炎的申请，该请求基于3期REGENCY试验（NCT04221477）的数据以补充生物制品许可申请（sBLA）的形式提交。FDA现在预计在10月之前做出关于奥滨尤妥珠单抗批准用于狼疮性肾炎的最终决定。今年2月，3期REGENCY试验的详细分析发表在《新英格兰医学杂志》上。该研究表明，完全肾反应（CRR）的主要终点有统计学意义和临床意义的改善，显示46.4%的奥滨尤妥珠单抗联合标准疗法治疗的患者达到76周时的CRR，而单独接受标准治疗的患者只有33.1%达到。与此同时，补体水平也有临床意义的改善，抗dsDNA、疾病活动和炎症标志物也有所减少（图3）。图3 3期REGENCY试验结果图片来源：参考文献62.达匹罗珠单抗达匹罗珠单抗是由优时比和渤健联合开发的一种人源化聚乙二醇化抗CD40L Fab片段，目前正在进行3期临床试验，用于治疗中度至重度SLE。去年9月，优时比和渤健宣布达皮罗珠单抗的3期PHOENYCS GO研究的积极顶线结果：与安慰剂相比，达皮罗珠单抗组的BICLA反应率显著高于安慰剂组（49.5%vs.34.6%），中度至重度疾病活动得到更大的改善。在测量疾病活动和发作的关键次要终点中观察到临床改善。基于PHOENYCS GO研究的成功结果，优时比和渤健于今年启动第二项3期临床试验PHOENYCS FLY。3.利替非利单抗利替非利单抗是由渤健研发的一种人源化IgG1单克隆抗体，可以靶向血液树突状细胞抗原2（BDCA2），通过抑制BDCA2减少包括I型干扰素（IFN-I）在内的炎性细胞因子的产生，从而调节红斑狼疮的病理机制。此前，利替非利单抗的Ⅱ期LILAC研究结果显示其显著降低皮肤疾病活动度的效果，与安慰剂组相比，能够有效缓解CLE患者的皮肤症状。目前，利替非利单抗正在进行TOPAZ-1和TOPAZ-2两项Ⅲ期临床试验，预计今年会出临床结果。红斑狼疮靶向治疗小分子药物除了生物制剂之外，小分子靶向药物也是红斑狼疮一大类主要治疗药物，治疗的靶点包括JAK、BTK、TLR7/8和蛋白酶体等，包括JAK抑制剂托法替布、巴瑞替尼、乌帕替尼和BTK抑制剂芬布替尼、奥布替尼等。1.托法替布托法替布是由辉瑞开发的一种泛JAK抑制剂，对JAK1/3作用更强，于2012年11月首次获批上市，目前已获批用于治疗多种免疫介导的疾病，包括类风湿关节炎、银屑病关节炎、溃疡性结肠炎、多关节型幼年特发性关节炎和强直性脊柱炎等。托法替布在SLE的一项Ib/IIa期、双盲、随机对照试验取得积极结果：托法替布在无意外严重不良事件（SAE）、疾病恶化或血栓栓塞的研究中耐受性良好。托法替布治疗后血脂谱、动脉硬度、I型IFN基因特征和循环中性粒细胞胞外陷阱得到改善。STAT4风险等位基因患者的实验室参数改善更稳健，这与SLE更严重的临床表型相关。2.乌帕替尼乌帕替尼是由艾伯维研发的一种选择性口服JAK1抑制剂，于2019年8月首次获得FDA，用于治疗多种自身免疫性疾病，包括类风湿性关节炎、银屑病关节炎、特应性皮炎等。去年10月，乌帕替尼单药或者与艾尔布替尼联用（ABBV-599高剂量）显示SLE疾病活动度显著改善并减少发作，并且在48周内耐受性良好。去年12月，ACR Convergence 2024会议上艾伯维公布结果显示，ABBV-599联合治疗组和乌帕替尼单药治疗组的患者疾病活动性降低，并且这种降低在试验的后半部分得以维持，长达104周。在研的靶向TLR 7/8抑制剂TLR7（Toll样受体7）和TLR8是模式识别受体，在自身免疫性疾病（如红斑狼疮）和某些炎症性疾病中，TLR7/8的过度激活可能导致炎症反应失控。因此，开发TLR7/8抑制剂成为治疗红斑狼疮的重要策略，这些抑制剂通过阻断TLR7/8的信号传导，减少炎症反应，降低疾病活动度。目前尚无用于治疗红斑狼疮的靶向TLR7/8抑制剂获批上市，在研的药物有Enpatoran和E6742等。1.EnpatoranEnpatoran是由Merck研发的一种潜在的皮肤型红斑狼疮（CLE）和SLE的同类首创口服疗法，可以选择性地阻断TLR7/8的激活，对其他内体TLR，即TLR3和TLR9没有影响。临床前PK研究表明Enpatoran具有高口服生物利用度，小鼠、大鼠和狗的生物利用度分别为100%、87%和84%。Enpatoran在体外测定中可以有效抑制人TLR7（hTLR7）、小鼠TLR7（m TLR7）和hTLR8，但不抑制mTLR8（图4）。图4 Enpatoran体外抑制结果图片来源：InvivoGen网站近期，Merck宣布了enpatoran的一项2期WILLOW研究（NCT05162586）队列A的积极数据，表明CLE和SLE伴活动性狼疮皮疹患者第16周时疾病活动度具有临床意义的降低，Enpatoran耐受性良好，未发现新的安全性信号。2.E6742E6742是由卫材株式会社（Eisai Co.,Ltd.）研发的一种选择性靶向TLR7/8双拮抗剂，通过抑制TLR7和TLR8的激活，减少促炎细胞因子和自身抗体的产生，用于治疗SLE。E6742的一些临床1/2期试验取得积极结果：E6742具有良好的安全性，耐受性良好，并且能够抑制干扰素基因标志（IGS）反应，在第12周时，E6742 100 mg组BICLA反应率为37.5%（3/8患者），200 mg组为57.1%（4/7患者），而安慰剂组为33.3%（3/9患者）（图5）。这些结果为E6742治疗SLE提供了首个临床证据，并支持进行更大规模、更长期的临床试验。图5 E6742的临床结果图片来源：参考文献12结语红斑狼疮是一种常见的慢性、反复发作的自身免疫性疾病，市场规模也在逐年扩大。目前已有靶向的生物制剂获批上市，尚无靶向的小分子抑制剂获批上市，与生物制剂相比，小分子抑制剂具有可口服等优点。然而用于治疗红斑狼疮的靶向小分子抑制剂研发并不顺利，有多款药物折戟在临床，包括JAK抑制剂Solcitinib、BTK抑制剂Evobrutinib、TLR7/8抑制剂MHV370等，近期，Merck的选择性口服TLR7/8抑制剂2期临床成功给该类药物的研发重拾了信心。参考文献1.Dominik Samotij and Adam Reich,Biologics in the Treatment of Lupus Erythematosus:A Critical Literature Review,Biomed Res Int.2019 Jul 18;2019:81423682.Roger A Levy et.al,10 Years of belimumab experience:What have we learnt?,Lupus.2021 Jul 8;30(11):1705–1721.3.BelimouMab市场规模，竞争市场和预测20324.Saphnelo(anifrolumab)approved in the US for moderate to severe systemic lupus erythematosus5.RemeGen’s Telitacicept Shows Best-in-Class Efficacy in Phase 3 Trial for Generalized Myasthenia Gravis6.R.A.Furie et.al,Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis,The New England Journal of Medicine 喜欢我们文章的朋友点个“在看”和“赞”吧，不然微信推送规则改变，有可能每天都会错过我们哦~免责声明“汇聚南药”公众号所转载文章来源于其他公众号平台，主要目的在于分享行业相关知识，传递当前最新资讯。图片、文章版权均属于原作者所有，如有侵权，请在留言栏及时告知，我们会在24小时内删除相关信息。信息来源：药智网往期推荐本平台不对转载文章的观点负责，文章所包含内容的准确性、可靠性或完整性提供任何明示暗示的保证。

临床3期上市批准ASH会议临床2期siRNA

2025-05-21

·药明康德

超90%患者达成缓解！潜在“first-in-class”小分子3期试验即将启动

德国默克（Merck KGaA）今日公布其潜在“first-in-class”口服小分子enpatoran在临床2期试验WILLOW中的积极结果。在接受enpatoran治疗的皮肤红斑狼疮（CLE）和伴有活动性狼疮皮疹的系统性红斑狼疮（SLE）患者中，超过90%患者的疾病活动度具有临床意义的降低。基于这些结果，德国默克正在与监管单位讨论全球3期临床试验启动的相关事宜。红斑狼疮是一种慢性自身免疫性疾病，可影响身体的多个部位，包括皮肤、关节、肾脏和其他器官。当免疫系统错误地攻击健康组织时，会导致炎症、疼痛和潜在的器官损伤。狼疮有多种类型，SLE和CLE是两种主要形式。症状从轻微到危及生命不等，通常包括疲劳、关节疼痛、皮疹和器官受累。狼疮对女性的影响尤为严重，尽管有可用的治疗方法，但由于疗效有限或副作用，许多患者的需求仍未得到满足。Enpatoran是一种潜在“first-in-class”的选择性Toll样受体（TLR）7/8抑制剂。通过抑制TLR7/8的激活，enpatoran可能有助于减少促炎细胞因子和自身抗体的产生，从而可能抑制狼疮慢性炎症和疾病进展的潜在机制。▲口服TLR7/8抑制剂有潜力成为狼疮的“first-in-class”疗法（图片来源：参考资料[2]）WILLOW是一项全球性、多中心、随机、安慰剂对照的临床2期研究，评估三种剂量的enpatoran（25 mg、50 mg和100 mg，每日两次）与安慰剂加标准治疗（SoC）在24周内的效果。该研究采用独特的设计，涵盖两个狼疮队列，包括活动性SLE和CLE患者。队列A专注于CLE或伴有活动性狼疮皮疹的SLE患者，并使用皮肤红斑狼疮疾病面积和严重程度指数活动度（CLASI-A）评分评估器官特异性疾病活动度，这是CLE研究中一个明确定义的终点，用于测量黏膜皮肤表现的不同方面。队列B则旨在通过BICLA应答终点评估enpatoran对SLE患者全身疾病活动度的影响。分析显示，队列A达到了其主要终点，患者显示出剂量-反应关系，并在第16周时其CLASI-A评分出现具有临床意义的改善（p=0.0002）。此外，在第24周时，接受enpatoran治疗的患者中高达91.3%达到CLASI-50应答（较基线改善≥50%），高达60.9%达到CLASI-70应答（较基线改善≥70%），而安慰剂组的这一比例分别为38.5%和11.5%。图片来源：123RF此外，队列A中enpatoran的治疗还导致患者的干扰素基因特征评分的快速降低，从第2周开始并持续至第24周，证实了TLR7/8通路在CLE干扰素激活中的作用。在该队列中，enpatoran耐受性良好，安全性可控，与之前的研究一致，未发现新的安全性信号。而WILLOW研究的队列B则未达到剂量应答的主要终点，但在预设亚组中观察到了潜在的疗效结果。德国默克预计将在欧洲风湿病协会联盟大会（EULAR 2025）上公布该队列的完整结果。参考资料：[1] Merck Presents Positive Phase 2 Data for Enpatoran Demonstrating Reduction in Disease Activity in Patients with Cutaneous Lupus Erythematosus (CLE) and Systemic Lupus Erythematosus (SLE) with Active Lupus Rash. Retrieved May 21, 2025 from https://www.businesswire.com/news/home/20250521318757/en/Merck-Presents-Positive-Phase-2-Data-for-Enpatoran-Demonstrating-Reduction-in-Disease-Activity-in-Patients-with-Cutaneous-Lupus-Erythematosus-CLE-and-Systemic-Lupus-Erythematosus-SLE-with-Active-Lupus-Rash[2] R&D UPDATE CALL 2021. Retrieved November 28, 2021, from https://www.emdgroup.com/investors/events-and-presentations/conferences-and-roadshows/2021/us/211122_RD_UpdateCall_Final_NA.pdf免责声明：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。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。👇 分享，点赞，在看，聚焦全球生物医药健康创新

临床结果临床2期siRNA临床3期ASH会议

2025-05-21

·FierceBiotech

Merck KGaA shares data justifying pushing lupus drug into phase 3—despite recent setback

Enpatoran demonstrated a clinically meaningful improvement at week 16 as measured by the CLE Disease Area and Severity Index.\n Despite Merck KGaA’s lupus drug failing to prove itself against one form of the autoimmune disease, the German drugmaker has now shared the data to back up its belief that the therapy still has promise.Merck had evaluated the oral TLR7/8 inhibitor, called enpatoran, in the phase 2 WILLOW study that separately assessed the drug in two forms of lupus. Peter Guenter, CEO of healthcare at Merck, disclosed back in October 2024 that the primary endpoint had been reached for a cohort of the trial involving patients with either cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) that included organ-specific disease activity.At the time, Guenter claimed this portion of the study had found “very strong and unambiguous proof of concept in cutaneous lupus.” However, the company didn’t offer up detailed data as proof.Concerns about the viability of enpatoran mounted in March of this year, when Merck disclosed that the drug had failed to hit the key endpoint of the other cohort of the trial, which was focused on patients with SLE only. The German company insisted at the time that it had seen “promising responses” in predefined subgroups of patients of the trial, which supported further development.Now, Merck has offered up data from the successful first cohort to justify its intention to push the enpatoran program into phase 3. Specifically, enpatoran demonstrated a clinically meaningful improvement at week 16 as measured by the CLE Disease Area and Severity Index.By week 24, 91.3% of patients had seen a 50% of greater improvement in this score from baseline, while 60.9% had seen a 70% or greater improvement. These changes compared with a 38.5% and 11.5% rate, respectively, in the placebo cohort.These patients also showed that enpatoran was well-tolerated and “exhibited a manageable safety profile consistent with previous studies, with no new safety signals identified,” Merck said.“We are encouraged by the WILLOW results, where we observed clinically meaningful efficacy with a favorable safety profile in people living with lupus rash,” said Jan Klatt, Head of Development Unit Neurology & Immunology for Merck Healthcare. “Based on these results, discussions with health authorities on a global phase 3 program with enpatoran are underway.”The pharma was able to use data from the CLE cohort to back up its premise that selectively blocking the activation of toll-like receptors 7 and 8, which are associated with severe lupus cases, can increase the effectiveness of treatment. In fact, enpatoran led to a rapid reduction in interferon gene signature scores beginning at week 2 and maintained to week 24, Merck said.Enpatoran, which Merck is also studying in idiopathic inflammatory myopathies, is one of the two most advanced assets in the company’s neurology and immunology pipeline. Cladribine, the other advanced candidate, is in phase 3 development as a treatment for generalized myasthenia gravis.

临床结果临床3期临床2期

100 项与 Enpatoran 相关的药物交易

登录后查看更多信息

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
皮肌炎	临床2期	美国	Merck KGaA	2023-01-19
皮肌炎	临床2期	捷克	Merck KGaA	2023-01-19
皮肌炎	临床2期	希腊	Merck KGaA	2023-01-19
皮肌炎	临床2期	意大利	Merck KGaA	2023-01-19
皮肌炎	临床2期	波兰	Merck KGaA	2023-01-19
皮肌炎	临床2期	西班牙	Merck KGaA	2023-01-19
皮肌炎	临床2期	英国	Merck KGaA	2023-01-19
盘状红斑狼疮	临床2期	美国	R-Pharm Germany GmbH	2022-02-14
盘状红斑狼疮	临床2期	日本	R-Pharm Germany GmbH	2022-02-14
盘状红斑狼疮	临床2期	阿根廷	R-Pharm Germany GmbH	2022-02-14

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


NCT05162586 (ACR2022) 人工标引	临床1期	-	36	Enpatoran	蓋願膚鹽顧淵顧餘觸鬱(遞獵觸鹽繭願築壓鑰窪) = Cmax: 0.9409 [0.7855–1.1270]; AUC0-inf: 0.8959 [0.7497–1.0704] and AUC0-tlast: 0.8963 [0.7511–1.0695]). 夢餘顧齋簾範鏇選糧夢 (繭膚觸鹹築餘齋廠選夢 ) 更多	积极	2022-09-12
NCT04448756 (ANEMONE, CTgov)	临床2期	新型冠状病毒感染	149	Placebo (Placebo)	鑰繭夢遞憲簾構選衊廠(廠鏇製糧壓夢積繭襯鬱) = 鑰觸範鹹醖顧齋築繭鏇觸憲糧襯淵蓋選願窪壓 (蓋繭憲鏇襯衊築願襯築, 選鑰鏇壓構構構鹽鏇鹹 ~ 廠選築鑰簾襯選齋窪餘) 更多	-	2022-06-06
				M5049 (M5049 100 mg)	鑰繭夢遞憲簾構選衊廠(廠鏇製糧壓夢積繭襯鬱) = 繭鬱襯糧餘鏇廠鏇齋鹹觸憲糧襯淵蓋選願窪壓 (蓋繭憲鏇襯衊築願襯築, 壓鬱醖觸遞製願遞構鹽 ~ 選遞窪鏇鹹艱鬱壓鏇願) 更多
NCT04448756 (ANEMONE, EULAR2022)	临床2期	新型冠状病毒感染 cytokines \| C-reactive protein \| D-dimer ... 更多	149	Enpatoran 50 mg BID	艱獵獵廠簾膚鹹醖餘窪(觸鏇鬱膚壓夢夢衊餘遞) = 鏇鹹襯獵憲獵繭觸繭艱鹹網餘範製觸蓋鹽餘襯 (糧蓋壓鏇遞繭襯衊獵觸 ) 更多	积极	2022-06-01
				Enpatoran 100 mg BID	艱獵獵廠簾膚鹹醖餘窪(觸鏇鬱膚壓夢夢衊餘遞) = 膚繭憲獵憲獵獵範遞鑰鹹網餘範製觸蓋鹽餘襯 (糧蓋壓鏇遞繭襯衊獵觸 ) 更多
NCT03676322 (Pubmed) 人工标引	临床1期	自身免疫性疾病	96	M5049 (single-dose)	範遞衊鬱網淵壓觸遞淵(壓鏇觸壓構構簾廠構構) = 衊繭廠壓夢鏇齋選鬱繭鏇顧構願糧構遞簾夢廠 (襯繭蓋選糧淵觸鬱艱構 ) 更多	积极	2021-10-01
				M5049 (multiple-dose)	範遞衊鬱網淵壓觸遞淵(壓鏇觸壓構構簾廠構構) = 鏇憲糧憲窪衊鏇憲醖網鏇顧構願糧構遞簾夢廠 (襯繭蓋選糧淵觸鬱艱構 )