A Phase 1, Open-Label Window-of-Opportunity Study to Assess the Pharmacokinetics, Pharmacodynamics and Central Nervous System (CNS) Penetration of Xevinapant in Preoperative Subjects With Recurrent High-Grade Glioma (rHGG)

Researchers will investigate the ability of Xevinapant to cross the blood-brain barrier and exert anti-tumor effects on rHGG through activation of apoptosis. Researchers hypothesize that oral administration of Xevinapant has acceptable safety and tolerability in patients with recurrent HGG and demonstrate pharmacokinetic and pharmacodynamic effects in HGG tumors. To that end, Researchers will engage in a phase I "window of opportunity" translational clinical trial in patients undergoing a clinically-indicated craniotomy for resection of recurrent tumors to evaluate the impact of treatment on rHGG.

开始日期2024-07-22

申办/合作机构

H. Lee Moffitt Cancer Center & Research Institute, Inc.

[+1]

NCT06084845

/ Withdrawn临床2期IIT

Phase II Trial of Xevinapant and Chemoradiotherapy in Adjuvant Treatment for Patients With Head and Neck Squamous Cell Carcinoma With High Risk Pathologic Features

This phase II trial compares the effect of usual radiation therapy with cisplatin/carboplatin (chemoradiation) to the addition of xevinapant with chemoradiation in patients with head and neck cancer. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Xevinapant is a first-in-class antagonist of inhibitor of apoptosis (programmed cell death) proteins (IAPs), which leads to tumor cell death and enhances tumor cell sensitivity to chemotherapy and radiotherapy. Giving xevinapant with chemoradiation may be more effective in preventing head and neck cancer from growing or spreading than chemoradiation alone.

开始日期2024-04-12

申办/合作机构

ECOG-ACRIN Medical Research Foundation, Inc.

[+1]

NCT06110195

/ Terminated临床1期IIT

A Phase I Study of Xevinapant With Radiation and Concurrent Carboplatin and Paclitaxel in Patients Ineligible for Cisplatin With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

The goal of this clinical trial is to determine the best safe dose of xevinapant that can be given in combination with chemotherapy and radiation in patients with head and neck cancer. Up to 4 doses of xevinapant will be tested in the dose escalation portion of the study. After the best safe dose is found during escalation, an additional group of participants will be enrolled at that dose to learn more about the treatment combination (dose expansion).
The main question[s] it aims to answer are:
* what is the maximum safe dose that can be given
* what dose should be used in subsequent (phase 2) trials
Participants will receive xevinapant in combination with paclitaxel and carboplatin chemotherapy and radiation. Treatment will be given in 3-week cycles for 3 cycles.

开始日期2024-01-24

申办/合作机构

The University of Chicago

[+1]

100 项与 Xevinapant 相关的临床结果

登录后查看更多信息

100 项与 Xevinapant 相关的转化医学

登录后查看更多信息

100 项与 Xevinapant 相关的专利（医药）

登录后查看更多信息

220

项与 Xevinapant 相关的文献（医药）

2026-03-01·Clinical Pharmacology in Drug Development

Absolute Bioavailability and Absorption, Distribution, Metabolism, and Excretion of [ ¹⁴ C]Xevinapant, a Potent, Oral, Small‐Molecule IAP Inhibitor

Article

作者: Roubaudi‐Fraschini, Marie‐Claude ; Nicolas‐Metral, Valérie ; Rohdich, Felix ; Menetrey, Annick ; Vugmeyster, Yulia ; Zhao, Yuan ; Tat, Tri ; Scheible, Holger ; Venkatakrishnan, Karthik

Abstract:

This Phase 1, open‐label, 2‐part, single‐dose study aimed to investigate the pharmacokinetics, metabolism, and excretion of xevinapant, a small molecule inhibitor of apoptosis proteins (IAPs), in healthy male subjects. Part 1 focused on determining the mass balance recovery, pharmacokinetics, and metabolic profile of [ 14 C]xevinapant following a single oral dose of 200 mg. Part 2 aimed to determine the absolute oral bioavailability of xevinapant by evaluating the pharmacokinetics of an oral dose of 200 mg xevinapant in comparison to an intravenous microtracer dose of [ 14 C]xevinapant using accelerator mass spectrometry. After oral administration, xevinapant was rapidly absorbed, with a median time to maximum concentration of 0.5 h and a geometric mean half‐life of 13.2 h. The principal route of excretion of drug‐related material was fecal, accounting for 60.2% of the administered dose, while 33.3% was excreted in urine. Renal clearance accounted for 18.4% of total clearance. In addition to xevinapant, seven metabolites were structurally characterized in the samples analyzed. The principal route of metabolism was dealkylation to form metabolite D‐1143‐MET1, with secondary metabolism by oxidation. The major circulating components in plasma were xevinapant and D‐1143‐MET1 (inactive on IAPs), which represented 28% and 42% of the total drug‐related exposure, respectively. The absolute oral bioavailability of xevinapant was determined to be 57.8%. The clearance of [ 14 C]xevinapant was 12.2 L/h and the volume of distribution at steady‐state was 75.3 L. Xevinapant was well tolerated in healthy male subjects, with no clinically significant findings in clinical laboratory evaluations, vital signs, ECG, or physical examinations.

2025-11-26·XENOBIOTICA

Article

作者: Richter, Lilian H.J. ; Maurer, Christine K. ; Rohdich, Felix ; Hagel, Marlene ; Menetrey, Annick ; Nachtigall, Jonny ; Massiere, Frederic ; Jacob, Dominik ; Lang, Benedikt ; Stelz, Christian ; Scheible, Holger ; Gradhand, Ulrike

Xevinapant, a drug previously under development for head and neck cancer, was investigated to determine its intrinsic clearance (CL_int) in vitro and assess the involvement of CYP enzymes in its metabolism. Extensive in vitro studies showed very low turnover, necessitating advanced methodologies to accurately measure CL_int values.Two novel in vitro assays, using a modified suspension hepatocyte protocol or 3D hepatocyte spheroid cultures, allowed measuring hepatic turnover of xevinapant with very low CL_int values of 1.3 or 0.3 µL/min/10⁶ cells, respectively. Reaction phenotyping using specific inhibitors, enabled by enhanced detection capabilities in spheroids, identified primarily CYP3A (> 50%) as contributor to the hepatic metabolism of xevinapant.In vitro-in vivo extrapolation, in combination with data from the human mass balance study, revealed that hepatic metabolism, primarily mediated by CYP3A, accounts for approximately 30% of the overall clearance. The remaining clearance is renal (∼20%) and metabolic, but potentially extrahepatic (∼50%).This research highlights the importance and benefits of utilising advanced in vitro techniques, such as human hepatocyte spheroids, to accurately characterise drug metabolism, providing valuable insights for pharmacokinetic evaluations and, ultimately, supporting the development of a PBPK model and understanding the DDI risk of xevinapant.

2025-11-01·EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

IFN-γ enhances Poly(I:C)-induced necroptosis and immunogenic cell death via TLR3 upregulation in cholangiocarcinoma cells

Article

作者: Sae-Fung, Apiwit ; Lomphithak, Thanpisit ; Jitkaew, Siriporn ; Duangthim, Nattaya

Cholangiocarcinoma (CCA), a heterogeneous tumor arising in the bile ducts, is associated with unfavorable prognosis and high mortality rates due to limited effective treatment options. Though promising, immunotherapy is hindered by CCA's desmoplastic tumor microenvironment, known for its inflammatory and immunosuppressive characteristics, often termed a "cold tumor". Previously, we reported that Poly(I:C), a TLR3 agonist, synergizes with a Smac mimetic, an IAP antagonist, to trigger necroptosis when caspase activity is blocked. In this study, we aimed to evaluate rational combination strategies to advance Poly(I:C)-based necroptosis immunotherapy in preclinical models. Transcriptomic analysis of public CCA patient datasets revealed that low expression of TLR3, accompanied by low IFNG or IRF1 expression, is significantly associated with poorer prognosis. These findings highlight the clinical relevance of the IFN-γ/IRF1/TLR3 axis and support the development of therapies targeting this pathway. We further found that IFN-γ treatment increases TLR3 expression. Importantly, we demonstrated that IFN-γ could enhance Poly(I:C)-induced necroptosis and immunogenic cell death (ICD) when IAPs and caspases are inhibited by Smac mimetic and the pan-caspase inhibitor Z-VAD-FMK in human CCA cell lines. CU-CPT 4a, a highly selective TLR3 inhibitor, partially reduced this cell death. This indicates that the effect is mediated in part through TLR3. The combined effects were shown to depend on RIPK1/RIPK3/MLKL-induced necroptosis. Additionally, the dying cells released HMGB1, a marker of ICD, and their conditioned medium promoted dendritic cell maturation (CD80, CD86, HLA-DR), which is critical for antigen presentation and T-cell priming. From a personalized medicine perspective, TLR3, IFNG, and IRF1 expression levels may serve as predictive biomarkers to guide patient selection for TLR3 agonist-based therapies. These findings could advance TLR3 ligand, Poly(I:C)-based necroptosis cancer immunotherapy, alone or with immune checkpoint inhibitors, for CCA and possibly other cancers.

134

项与 Xevinapant 相关的新闻（医药）

2026-03-12

·CPHI制药在线

山巅之上的阴影：仿制药围城与研发折戟，默克的明天在哪里？

关注并星标CPHI制药在线 --扫码领取CPHI China2026展会门票-- 在医药界，默克（Merck KGaA）的名字几乎家喻户晓。这家百年老店经过“一战”的洗礼，引领了德国十九世纪的制药潮流，如今已发展一家覆盖生命科学、医药健康以及电子科技三大业务板块的多元化科技公司。一百多年来，默克可谓是全球制药界的常青树，然而即便站在山巅，也难抵御寒风。近日，默克在公布2025年财报的同时，宣布大砍肿瘤管线，并预计2026年公司营收增长最高仅2%，甚至可能下滑1%。业绩承压背后，默克制药业务的明天在哪里？专利防线被击穿，核心药物迎仿制药合围眼下，对默克医药业务影响最大的事件莫过于旗下核心药物Mavenclad 在美专利维权失利。这款药物于2019年获FDA批准，用于治疗成人复发型多发性硬化（RMS），其通过靶向淋巴细胞的DNA代谢，实现免疫调节，为MS治疗提供了一种独特的机制基础。而且Mavenclad在两个治疗年内仅需口服20天，即可实现长达数年的疾病缓解效果，这种便利性使其在依从性要求高的MS患者群体中备受欢迎，在竞争白热化的MS市场杀出了一条血路。 Mavenclad的上市，给默克带来了十足的底气，成为默克神经科学领域的支柱产品。2025年，其销售额高达12 亿欧元，同比上涨近17%。但2025年成为了这款药物在美国市场的分水岭。2025年10月，美国联邦巡回上诉法院敲定了默克两项Mavenclad给药方案专利无效的判决，后期公司的重审申请也被驳回。紧接着，仿制药企业迅速行动。加拿大Apotex公司的Mavenclad仿制药已获得FDA最终批准并上市，其他多家企业也获得了临时批准或正在研发仿制药，市场激烈竞争的架势已经摆开。默克在2026年的业绩指引里，直接明确表示，因仿制药竞争，自2026年3月起，Mavenclad在美国市场的销售将为零。而且，Mavenclad在欧洲市场的独占期将于2027年8月结束。在这种形势下，默克将2026年销售额预期定在200 亿至 210 亿欧元，同比可能微跌1%或微涨2%。除了核心产品业绩遭遇重创外，默克的创新药研发进展也不顺利。2024年6月，默克宣布终止IAP抑制剂Xevinapant+放化疗联合治疗局部晚期头颈癌的III期临床，起因是在中期分析中，Xevinapant组被判“难以达到主要终点”。该药是默克在2021年4月，以2.27亿美元预付款+8.56亿美元里程碑金额引进而来。此外，默克的免疫检查点抑制剂Bavencio在北美等市场由于受替代疗法冲击、销售呈现增速放缓趋势。面对核心药物销售崩塌，在研管线临床折戟的困境，默克不得不快速采取行动。应对危机，断臂求生面对经营危机，默克开始收缩管线。在2025年财报发布的同时，默克宣布，放弃收购SpringWorks所得的全部临床阶段肿瘤药，同时终止PARP1抑制剂M9466的研发，以及终止Ogsiveo的新适应症探索。 2025年4月底，默克与美国制药公司SpringWorks Therapeutics长达数月的收购谈判终告完成，默克将以每股47美元、总计39亿美元的股权价值全资收购SpringWorks Therapeutics。这是继2015年，以170亿美元收购美国试剂公司Sigma-Aldrich后，默克在医药领域规模最大的一笔交易。通过这次交易，默克将获得两款已获FDA批准的药物：用于治疗极罕见硬纤维瘤的 Ogsiveo，用于治疗神经纤维瘤病1型（NF1）的MEK抑制剂Gomekli，以及若干在研管线——针对实体瘤的RAF二聚体抑制剂 brimarafenib，针对Hippo突变实体瘤的TEAD抑制剂SW-682等，以巩固默克在肿瘤治疗领域的竞争力。如今距离完成收购仅不到一年的时间，默克便为优化研发资源配置，“及时止损”。 M9466的终止更令人唏嘘。M9466是一款选择性、高活性、可口服的PARP1小分子抑制剂，由恒瑞医药研发。2023年10月，默克以1.6亿欧元的首付款及高达14亿欧元的总交易额，引进了M9466，该产品曾被默克高管公开称赞“具有高度组合潜力”。但是随着PARP1抑制剂赛道已进入白热化竞争阶段，市场预期严重缩水，默克果断选择仍处于研发阶段的M9466。另外，默克还叫停了已上市药物Ogsiveo用于卵巢颗粒细胞瘤新适应症的探索试验。默克此次看似突然的砍管线，背后是业绩承压的无奈之举。未来的业绩支柱？默克在砍管线的同时，也在进行资源聚焦，默克首先选择力推 Precem-TcT，这是一款CEACAM5（癌胚抗原相关细胞粘附分子5）ADC，在治疗经过重度预治疗的结直肠癌（CRC）Ⅰ期临床中，客观缓解率（ORR）达31%，中位无进展生存期（mPFS）为6.9个月。基于此结果，默克决定跳级进入Ⅲ期临床，并在今年第二/三季度启动，反映了默克抢占先发优势的急迫性。此外，默克已与和誉医药合作，获得其CSF-1R小分子抑制剂Pimicotinib的全球商业化权益，该药于2025年12月获中国药监局批准上市，用于治疗无法手术切除或手术风险高的腱鞘巨细胞瘤（TGCT）。默克预计于2026年在美国递交上市申请。对于核心产品Mavenclad，默克并未完全放弃，而是转向下一代剂型与适应症扩展，以延长Mavenclad的生命周期：拓展儿科适应症，将Mavenclad的适用人群扩展至青少年MS患者，以获取新的市场独占期。联合疗法探索：研究Mavenclad与其他药物（如BTK抑制剂）的序贯疗法，将其作为免疫诱导剂，融入到更复杂的治疗方案中，从而跳出单纯的单药竞争。当下的默克，正站在一个尴尬的历史交汇点：一边是其赖以生存的核心产品正面临史上最猛烈的仿制药浪潮冲击，另一边则是寄予厚望的在研管线频频遭遇临床失败。当“现金牛”日渐衰老，而“新王”尚未加冕，默克的未来蒙上了一层厚厚的阴影。被寄予希望的CEACAM5 ADC、CSF-1R小分子抑制剂能给默克带来一个清晰的未来吗？我们拭目以待。主要参考资料： 1.https://www.fiercepharma.com/pharma/after-generic-defense-fails-merck-kgaa-expects-no-us-mavenclad-sales-after-march. 2.Kopetz S, Boni V, Kato K, Raghav KPS, Vieito M, Pallis A, Habermehl C, Siddiqui A, Courlet P, Sloot W, Raab-Westphal S, Hart F, Rodriguez-Rivera I. Precemtabart tocentecan, an anti-CEACAM5 antibody-drug conjugate, in metastatic colorectal cancer: a phase 1 trial. Nat Med. 2025 Jul 30. doi: 10.1038/s41591-025-03843-z. Epub ahead of print. PMID: 40739424. END 智药研习社近期直播来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

2026-03-11

·今日头条

中国创新药出海模式大变!恒瑞被“退货”后，新潮已起

引言：一场退货，掀翻中国创新药出海旧格局 2026年3月5日，一则消息震动整个医药圈：德国默克正式终止与恒瑞医药关于PARP1抑制剂HRS-1167的全球授权合作，这笔2023年签下、总金额高达14亿欧元（约合人民币超百亿元）的重磅交易，最终以“退货”收场。一时间，市场哗然：作为中国创新药“一哥”，恒瑞的海外授权被跨国药企终止，是否意味着中国创新药出海遇冷？曾经风靡的“卖青苗”模式，是否已经走到尽头？但真相恰恰相反。恒瑞被“退货”不是终点，而是中国创新药出海模式从1.0到3.0的关键转折点。一边是传统授权模式频频“翻车”，退货率攀升至40%；另一边是2026年开年仅2个月，中国创新药海外授权就达成44笔交易、总金额超532亿美元，创下历史新高。从“一锤子买卖”到“全球合伙人”，从“卖产品”到“卖技术平台”，从“被动授权”到“主动主导”，中国创新药出海正在经历一场彻底的模式革命。今天，我们以恒瑞“退货”事件为切口，深挖背后的行业真相，拆解2026年中国创新药出海的全新玩法，告诉你这场变革中，谁能抓住机遇，谁将被时代淘汰。一、恒瑞“退货”真相：不是药不行，是旧模式死了（一）事件还原：百亿交易终止，钱不退、药拿回 2023年10月，恒瑞医药与德国默克达成战略合作，默克以1.6亿欧元首付款（约12.3亿元人民币），拿下HRS-1167中国大陆以外的全球独家开发、生产及商业化权利，同时获得Claudin 18.2 ADC药物SHR-A1904的全球选择权，潜在总交易金额高达14亿欧元。这是恒瑞首次直接与跨国药企（MNC）达成重磅授权，被视为中国创新药出海的标志性事件。然而短短28个月后，合作戛然而止。默克给出的官方理由是：基于管线优先级排序，集中资源推进更具潜力的项目。但核心事实清晰： 1. 钱不用退：1.6亿欧元首付款已全额到账，协议无退款条款，恒瑞白拿12亿研发资金； 2. 药没毛病：HRS-1167处于临床Ib/II期，数据正常，终止原因与药物安全性、有效性无关； 3. 合作未断：2025年4月，双方已就另一款药物SHR7280达成新合作，默克仍认可恒瑞研发实力。（二）退货根源：跨国药企“断臂求生”，旧模式难以为继恒瑞被“退货”，本质是跨国药企战略收缩与赛道内卷双重压力下的必然结果，也是传统“授权出海”模式的集体困境。 1. 默克自身“爆雷”，砍管线保命默克核心在研药Xevinapant III期临床失败，PD-L1单抗Bavencio销售下滑，重磅药物Mavenclad面临专利悬崖，2026年全面收缩早期临床管线，不仅砍掉HRS-1167，连39亿美元收购的SpringWorks管线也全部清空。 2. PARP赛道挤爆，无利可图全球已有6款PARP抑制剂获批，国内4款纳入医保，2025年集采中奥拉帕利6家企业中标，原研阿斯利康直接丢标；第二代PARP1抑制剂全球40款进入临床，赛道内卷到“赔本赚吆喝”，默克果断放弃。 3. 旧模式致命缺陷：只卖权益，不掌话语权传统“license-out”模式，中国药企把海外权益一次性“卖断”，只赚首付款和微薄分成，后续临床、定价、商业化全由跨国药企掌控。一旦对方战略调整、资金紧张，项目就会被“弃子”，中国药企毫无反抗之力。数据显示，2020年中国药企62起海外授权，截至2025年已有25起终止，退货率高达40%。恒瑞不是第一个，也绝不会是最后一个。二、数据暴击：一边是退货潮，一边是出海狂潮（一）退货潮不止：旧模式批量淘汰恒瑞“退货”并非个例，2026年开年，宜明昂科两款抗癌药被美国Instil Bio终止授权；此前，多家创新药企海外合作因临床数据、资金问题夭折。但这并非行业衰退，而是行业洗牌：低质量、同质化、无差异化的“伪创新”被淘汰，真正有核心技术、全球竞争力的创新药，反而迎来出海黄金期。（二）出海狂潮来袭：2个月532亿，刷新历史纪录与退货潮形成鲜明对比的，是2026年中国创新药出海的爆发式增长： - 交易规模破纪录：截至2月25日，年内完成44笔海外授权，总金额532.76亿美元，超过2025年全年的1/3； - 单笔金额创新高：石药集团与阿斯利康达成185亿美元战略合作，刷新中国创新药出海单笔交易纪录；荣昌生物RC148授权艾伯维，交易总额56亿美元，首付款6.5亿美元； - 合作密度空前：信达生物+礼来（88.5亿美元）、前沿生物+GSK（9.5亿美元）、和铂医药+Solstice（12亿美元），重磅交易密集落地。一退一进之间，中国创新药出海完成结构性切换：从“拼数量、卖低价”的1.0时代，迈入“拼质量、掌话语权”的3.0时代。三、模式革命：从“卖青苗”到“全球合伙人”，四大新潮崛起恒瑞被“退货”后，中国创新药出海彻底抛弃“一锤子买卖”，四大全新模式崛起，重新定义全球医药合作规则。（一）模式一：授权+股权，深度绑定利益共同体告别单纯的“首付款+里程碑+销售分成”，**“授权+股权”**成为2026年出海主流模式，中国药企从“合作方”变成“股东”，风险共担、收益共享。 - 典型案例：和铂医药与Solstice Oncology合作，不仅获得5000万美元首付款，还拿到超5000万美元股权，深度参与全球开发； - 恒瑞新玩法：将GLP-1产品组合授权美国Hercules公司，同时获得其19.9%股权，既赚授权费，又享长期分红； - 核心优势：避免“退货即止损”，跨国药企不会轻易放弃股东资产，中国药企牢牢绑定长期收益。（二）模式二：联合开发（Co-Co），平等主导全球研发不再是中国药企“交项目”、跨国药企“做全球”，而是双方联合开发、分区域主导，中国药企掌握核心话语权。 - 典型案例：信达生物与礼来合作，信达主导药物发现至中国临床II期，礼来负责大中华区以外全球开发，双方按比例分摊费用、共享收益； - 武田+信达：114亿美元合作，双方共同开发3款产品，信达保留大中华区权益，美国市场共享利润，成为全球Co-Co模式范本； - 核心优势：中国药企从“技术提供者”升级为“全球运营参与者”，不再是被动授权，而是平等共创。（三）模式三：平台出海，从卖产品到卖“武功秘籍” 这是2026年最颠覆性的变化：中国药企不再只卖单个药物，而是输出底层技术平台，实现从“产品出海”到“技术出海”的跨越。 - 标杆案例：石药集团与阿斯利康合作，输出缓释给药技术平台+多肽AI发现平台，开发4款长效多肽药物，总金额185亿美元； - 本质升级：卖产品是“卖鱼”，卖平台是“卖渔具”，一次性输出技术，持续获得多个产品的收益，价值提升百倍； - 行业意义：标志中国创新药研发能力，从“跟跑”到“领跑”，获得全球顶级药企认可。（四）模式四：全链条出海，自主掌控全球商业化头部药企彻底摆脱“借船出海”，自建海外团队、自主申报、自主商业化，实现从研发到销售的全链条掌控。 - 恒瑞自救：HRS-1167权益收回后，恒瑞自主推进国内II期临床，布局联合疗法，重新寻找全球合作方，不再依赖单一跨国药企； - 复宏汉霖：汉斯状®在全球40多个国家获批，自主搭建海外商业化团队，实现区域精准出海； - 核心逻辑：把命运握在自己手里，不再看跨国药企脸色，赚取全产业链利润。四、赛道重构：这些领域，中国创新药领跑全球模式升级的同时，中国创新药出海的赛道格局也彻底重构，从单一肿瘤赛道，走向多领域全面开花，部分赛道实现全球领跑。（一）双抗/ADC：全球争抢的“黄金赛道” PD-1/VEGF双抗成为全球爆款，康方生物依沃西单抗头对头击败K药，荣昌生物RC148授权艾伯维，全球前十大跨国药企4家重仓中国双抗资产；ADC药物凭借高疗效、低毒性，成为海外授权热门，恒瑞、科伦博泰多款ADC出海。（二）GLP-1：代谢疾病全球争霸中国GLP-1研发速度、成本优势全球领先，石药SYH2802、先为达口服GLP-1纷纷出海，与跨国药企同台竞技，成为继双抗之后第二大出海赛道。（三）小核酸：前沿领域弯道超车小核酸被誉为“第三波创新浪潮”，中国药企在递送系统领域突破壁垒，前沿生物、瑞博生物与GSK、Madrigal合作，抢占全球基因沉默市场。（四）自免/罕见病：低风险高价值新蓝海跨国药企逐步转向临床终点清晰、政策风险低的自免、罕见病领域，中国药企在该领域的创新成果，成为出海新宠。五、深层逻辑：中国创新药出海，为何能完成模式逆袭？短短三年，中国创新药从“被退货”到“被疯抢”，从“卖青苗”到“卖平台”，背后是三大核心支撑，让全球药企不得不正视中国力量。（一）研发实力质变：从模仿到全球首创 2025年中国批准上市创新药76个，在研管线占全球30%，位居全球第二；从“快速跟进”到“全球首创（First-in-class）、同类最优（Best-in-class）”，中国创新药的临床数据、疗效安全性，达到全球标准。（二）临床效率碾压：成本低、速度快中国患者入组速度是欧美3倍，乳腺癌III期临床仅需8个月，美国需28个月；单个患者试验成本4.2万元，不到美国的1/5，高效低成本的临床资源，成为中国药企核心竞争力。（三）政策+资本双重加持国家药监局深化药品监管改革，加速创新药出海审批；高瓴、红杉等资本组建海外BD团队，礼来设立30亿美元中国基金，全球资本重仓中国创新药，为模式升级提供资金支撑。六、风险警示：出海新潮下，三大陷阱必须避开模式升级不代表“躺赢”，2026年中国创新药出海，仍有三大陷阱，稍有不慎就会重蹈“退货”覆辙。（一）警惕“伪创新”内卷扎堆PD-1、GLP-1等热门赛道，无差异化、无核心数据，即便签下授权，也会因赛道拥挤被终止，最终沦为“弃子”。（二）防范跨国药企“套路” 部分跨国药企以高额首付款为诱饵，锁定中国创新药，却因自身战略收缩搁置项目，中国药企虽不退款，但错失最佳商业化窗口期。（三）补齐国际化短板 FDA、EMA审批严格，CMC生产合规、临床数据全球认可、海外团队运营能力，仍是中国药企的短板，恒瑞“双艾”组合两次获FDA CRL，就是生产合规问题导致。七、未来展望：中国创新药出海，下一个十年怎么走？恒瑞被“退货”，是中国创新药出海的成人礼。它宣告了“单纯授权”旧模式的终结，也开启了“平等合作、技术输出、自主掌控”的新时代。未来5年，中国创新药出海将呈现三大趋势： 1. 模式常态化：授权+股权、联合开发、平台出海成为主流，退货率逐步下降，交易质量持续提升； 2. 价值高端化：从小分子、抗体，到小核酸、CGT、AI制药，中国药企抢占全球前沿技术高地； 3. 格局全球化：诞生一批全球医药巨头，中国创新药从“中国智造”变成“全球标准”，彻底改变全球医药格局。结语：退货不是终点，而是新的起点恒瑞被“退货”，不是中国创新药的失败，而是行业升级的必然。曾经，我们靠“卖青苗”换取微薄收益，看人脸色、任人摆布；如今，我们靠核心技术、全球视野，成为跨国药企的“全球合伙人”，输出技术、掌控话语权。旧模式已死，新潮已起。中国创新药出海，早已不是“能不能出去”的问题，而是“如何主导全球”的问题。恒瑞的教训，让所有中国药企清醒：只有掌握核心技术、坚守创新本质、升级合作模式，才能在全球医药舞台上，站稳脚跟、赢得尊重。这场变革，才刚刚开始。中国创新药的黄金时代，正在到来！

引进/卖出抗体药物偶联物并购申请上市临床3期

2026-02-12

·EndPoints

Sanofi’s new CEO Belén Garijo gets frosty reception as Dupixent challenge awaits

The negative reaction to the impending departure of Sanofi CEO Paul Hudson, and Merck KGaA leader Belén Garijo as his replacement, is perhaps surprising given the French company’s muted performance under Hudson’s leadership. Sanofi’s shares fell about 3% in Paris and 4% in New York, a cold shoulder that may simply reflect the scale of the challenge that Garijo faces when she takes the reins in late April. She’ll have less than five years before the company’s immunological juggernaut Dupixent goes generic. Investors are concerned Garijo doesn’t have a track record of delivering R&D productivity at Merck KGaA, Jefferies managing director Michael Leuchten told Endpoints News in an interview. He considers that criticism “a little unfair” because the German conglomerate focused its capital allocation on areas other than pharma. “We thought the negative reaction on share price was harsh and kind of misses some of the nuances of what may be going on here,” Leuchten said. The company’s shares have lost about a quarter of their value in the past year. Garijo and her team will have to find pragmatic ways to extend Dupixent’s exclusivity, which could be possible through patent settlements and building on its joint venture with Regeneron, because there isn’t time to “rebuild an R&D organization from scratch” before Dupixent’s patent expires, Leuchten said. “One scenario that I think is possible is for Sanofi to go and acquire some assets that they fully fund and put those assets into the joint venture,” Leuchten said. Sanofi’s strategic priorities will remain unchanged under Garijo, a company spokesperson told Endpoints in an email. At Merck KGaA, Garijo’s history of dealmaking wasn’t scintillating. The biggest deal the company closed under her leadership was the $3.9 billion SpringWorks acquisition , and the rare cancer drugs Merck KGaA obtained haven’t been particularly lucrative so far. Another aspect driving some of the skepticism is that Garijo has had trouble delivering on promises in the past. In a letter in early 2022, she set out a goal for Merck KGaA known as “25 by 25” — achieving €25 billion ($27 billion) in total sales by 2025. The group won’t report its 2025 earnings until next month, but last October it guided to 2025 net sales between €20.8 billion and €21.4 billion. This missed goal is undeniably partly due to pipeline misfires. The failure of Merck KGaA’s evobrutinib in multiple sclerosis in late 2023 was followed by the cancellation of the pivotal trial of the head and neck cancer drug xevinapant in June 2024, after an interim analysis concluded the study was headed for failure. But Sanofi’s efforts to improve its drug development under Hudson didn’t always go as planned either. In 2019, at the beginning of his tenure as CEO, Hudson highlighted six programs as priorities. Two made it to market, Qfitlia (for hemophilia) and Beyfortus (for respiratory syncytial virus), but the others have either disappointed or failed entirely. Hudson also stopped developing a GLP-1 program for diabetes called efpeglenatide, just as other drugmakers were stepping up development efforts of this mechanism in obesity. There is no guarantee that asset would have gone on to do well, but the decision looks poor in retrospect. Sanofi’s current strategy involves going big on vaccines and investing in deals with a budget of up to €15 billion to spend across four key therapeutic areas: immunology, vaccines, neurology and rare diseases. This seems unlikely to compensate for Dupixent’s loss of exclusivity, since the drug accounted for 36% of Sanofi’s 2025 revenues. It was perhaps Sanofi’s eagerness on immunology that led things to go wrong at the French drugmaker under Hudson in the first place, Leuchten said. Sanofi assumed that immunology can be approached rationally and with acceptable risk, but time has shown that the space is “a lot more complicated than we thought,” Leuchten said. “The placebo response rates are all over the shop, you get intratrial variability, so the rational approach doesn’t work as well as anybody thought.” Sanofi’s change at the top seems to have happened fast; CEO transitions can be planned around a year in advance in the normal run of things. But Sanofi has ousted leaders with unceremonious haste before. In 2014 it sacked then-CEO Chris Viehbacher after a boardroom clash over Viehbacher’s management style.

高管变更

100 项与 Xevinapant 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16305

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
头颈部鳞状细胞癌	临床3期	中国	默克雪兰诺（北京）医药研发有限公司	2022-10-06
头颈部鳞状细胞癌	临床3期	中国台湾	默克雪兰诺（北京）医药研发有限公司	2022-10-06
头颈部肿瘤	临床3期	美国	Debiopharm International SA	2022-01-30
局部晚期头颈部鳞状细胞癌	临床3期	美国	Merck KGaA	2020-08-07
局部晚期头颈部鳞状细胞癌	临床3期	中国	Merck KGaA	2020-08-07
局部晚期头颈部鳞状细胞癌	临床3期	日本	Merck KGaA	2020-08-07
局部晚期头颈部鳞状细胞癌	临床3期	阿根廷	Merck KGaA	2020-08-07
局部晚期头颈部鳞状细胞癌	临床3期	澳大利亚	Merck KGaA	2020-08-07
局部晚期头颈部鳞状细胞癌	临床3期	奥地利	Merck KGaA	2020-08-07
局部晚期头颈部鳞状细胞癌	临床3期	比利时	Merck KGaA	2020-08-07

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


NCT05386550 (XRay Vision, CTgov)	临床3期	头颈部鳞状细胞癌 \| 局部晚期头颈部鳞状细胞癌	166	IMRT+Xevinapant (Xevinapant +IMRT)	夢窪廠蓋壓築範顧築簾(鹽鹽膚鑰繭衊積壓願衊) = 艱襯淵築夢繭願襯網觸簾蓋膚簾餘壓鏇蓋膚糧 (製鹹淵衊壓醖構鏇窪觸, 願積鑰顧糧繭積遞簾齋 ~ 積醖憲鏇憲鏇鹽壓遞選) 更多	-	2026-02-19
				Placebo (Placebo +IMRT)	夢窪廠蓋壓築範顧築簾(鹽鹽膚鑰繭衊積壓願衊) = 獵憲繭鬱淵憲願製壓餘簾蓋膚簾餘壓鏇蓋膚糧 (製鹹淵衊壓醖構鏇窪觸, 淵積醖壓廠鑰衊襯夢艱 ~ 鬱艱選願襯艱憲醖艱選) 更多
NCT04459715 (TrilynX, Pubmed \| J Clin Oncol)	临床3期	局部晚期头颈部鳞状细胞癌	730	Xevinapant plus CRT	積範獵鹽鏇夢糧廠艱襯(膚糧築鑰鹽餘願鏇鹹構) = 構鑰鑰簾獵鹽鏇鑰憲糧憲餘夢憲獵積網襯鏇糧 (壓選鏇壓獵壓淵遞簾夢, 14.5 ~ NE) 更多	不佳	2025-10-10
				Placebo plus CRT	積範獵鹽鏇夢糧廠艱襯(膚糧築鑰鹽餘願鏇鹹構) = 淵糧夢積憲艱願蓋顧範憲餘夢憲獵積網襯鏇糧 (壓選鏇壓獵壓淵遞簾夢, 21.0 ~ NE) 更多
NCT04459715 (TrilynX, CTgov)	临床3期	局部晚期头颈部鳞状细胞癌	730	carboplatin+Cisplatin+Debio 1143 (Sequence 1: Debio 1143 + CRT)	簾鏇構願積衊顧築夢獵(襯築簾蓋艱襯醖醖鑰夢) = 鏇糧鹽膚蓋夢築窪壓糧繭壓鏇網窪願淵築網餘 (範鹹膚顧憲鑰膚鏇顧觸, 齋鹹餘範餘網窪顧顧積 ~ 積獵蓋壓蓋顧築顧積網) 更多	-	2025-10-08
				Placebo (Sequence 2: Placebo + CRT)	簾鏇構願積衊顧築夢獵(襯築簾蓋艱襯醖醖鑰夢) = 糧膚蓋繭製糧繭製衊積繭壓鏇網窪願淵築網餘 (範鹹膚顧憲鑰膚鏇顧觸, 淵願築獵觸遞鏇積鏇鑰 ~ 鑰製夢構鹽觸糧鑰憲製) 更多
NCT06056310 (CTgov)	临床1期	口咽肿瘤 \| 局部晚期头颈部鳞状细胞癌 \| 头颈部肿瘤	18	Cisplatin+Xevinapant	壓壓憲繭醖選鏇夢憲遞 = 顧製壓選網糧餘構窪窪獵觸鬱鑰鹽觸膚夢壓鹽 (獵齋夢遞顧鹹製鏇鑰衊, 襯繭選網齋簾糧膚遞憲 ~ 膚鬱製鬱憲選廠簾鬱顧) 更多	-	2025-09-29
NCT05519540 (CTgov)	临床1期	-	24	Xevinapant (Debio 1143) (Group 1: Japanese Participants: Xevinapant (Debio 1143))	鏇簾繭築顧範鏇餘鏇簾(顧壓糧衊製襯簾網夢顧) = 廠衊範築憲壓願選衊選鬱齋憲艱獵艱選繭鏇醖 (餘繭夢繭繭憲築窪獵鹽, 34.6) 更多	-	2025-08-20
				Xevinapant (Debio 1143) (Group 2: Non-Japanese East Asian Participants: Xevinapant (Debio 1143))	鏇簾繭築顧範鏇餘鏇簾(顧壓糧衊製襯簾網夢顧) = 鹹選膚網夢鑰餘簾簾製鬱齋憲艱獵艱選繭鏇醖 (餘繭夢繭繭憲築窪獵鹽, 21.4) 更多
NCT03270176 (Phase Ib study, Pubmed \| Ther Adv Med Oncol)	临床1期	晚期非小细胞肺癌 plasma IL-10 \| IL-1β \| IL-13 ... 更多	-	Xevinapant RP2D + Avelumab	製繭憲壓願膚簾鹽餘願(鬱淵醖壓夢淵膚繭艱構) = n = 13 (34.2%) 憲艱鹹淵積築積襯製簾 (構遞簾鏇遞範網鬱選夢 ) 更多	不佳	2025-01-01
NCT04459715 (TrilynX, BusinessWire) 人工标引	临床3期	局部晚期头颈部鳞状细胞癌	-	xevinapant + CRT	繭淵艱構鏇夢構選醖淵(鏇觸窪醖鹽觸衊觸觸製) = the trial would be unlikely to meet its primary objective of prolonging event-free survival. 壓網鬱鑰壓壓鏇顧網廠 (遞壓鹹繭憲壓齋衊衊窪 ) 未达到	不佳	2024-06-24
NCT02022098 (ASCO2024) 人工标引	临床2期	头颈部鳞状细胞癌	96	Xevinapant + CRT	齋衊糧願鏇製鬱鏇壓範(構夢顧蓋網窪鏇簾觸構) = 繭觸襯膚顧壓鑰顧餘鑰遞餘醖襯築膚範衊鹹衊 (觸簾襯積構壓糧壓選築 ) 更多	积极	2024-05-24
				Placebo + CRT	齋衊糧願鏇製鬱鏇壓範(構夢顧蓋網窪鏇簾觸構) = 築鹹觸餘築觸鹹憲願願遞餘醖襯築膚範衊鹹衊 (觸簾襯積構壓糧壓選築 ) 更多
NCT04122625 (SMARTPLUS-106, CTgov)	临床1/2期	女性生殖器官肿瘤 \| 原发性腹膜癌 \| 实体瘤 ... 更多	46	Nivolumab+Debio 1143 (Part A - Debio 1143 150 mg + Nivolumab)	糧醖醖齋鬱襯鏇鑰遞醖 = 製鹽鏇鑰觸鬱積膚蓋餘鑰夢壓膚醖壓鹹餘壓糧 (蓋襯鑰衊顧淵襯願餘遞, 觸夢鹽窪醖範積糧顧襯 ~ 網構鹹壓觸製蓋積鹹齋) 更多	-	2023-06-12
				Nivolumab+Debio 1143 (Part A - Debio 1143 200 mg + Nivolumab)	糧醖醖齋鬱襯鏇鑰遞醖 = 鑰鏇糧鏇獵糧網艱築鏇鑰夢壓膚醖壓鹹餘壓糧 (蓋襯鑰衊顧淵襯願餘遞, 鹽憲餘衊廠簾膚積壓憲 ~ 淵構醖壓襯鬱遞顧簾構) 更多
AACR2023 人工标引	临床1期	非小细胞肺癌	38	xevinapant 200 mg/day+avelumab 10 mg/kg	鏇繭製淵選鬱夢願齋艱(齋衊簾醖餘膚鹹製膚餘) = 衊範積獵醖齋齋鹽觸遞獵願餘鹹窪簾夢選襯製 (壓積餘艱範鑰觸選壓憲, 2.9 ~ 24.8) 更多	不佳	2023-04-14