A Randomized Phase II Study of Tepotinib With or Without Ramucirumab in Participants With MET Exon 14 Skipping Positive Stage IV or Recurrent Non-Small Cell Lung Cancer (LUNG-MAP SUB-STUDY)

This phase II Expanded Lung-MAP treatment trial tests tepotinib with or without ramucirumab for the treatment of patients with advanced non-small cell lung cancer that has spread from where it first started (primary site) to other places in the body (stage IV) or that has come back after a period of improvement (recurrent). Tepotinib is used in patients whose cancer has a mutated (changed) form of a gene called MET. It is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal MET protein that signals tumor cells to multiply. This helps slow or stop the spread of tumor cells. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Giving tepotinib with ramucirumab may lower the chance of the cancer from growing or spreading in patients with stage IV or recurrent non-small cell lung cancer.

开始日期2024-08-08

申办/合作机构

Eli Lilly & Co.

[+2]

NCT06083857 / Recruiting临床1/2期IIT

An Open-Label Phase I/II Study to Evaluate the Safety and prelimiBasnary Efficacy of Amivantamab and Tepotinib Combination in MET-altered Non-small Cell Lung Cancer (NSCLC)

To learn if the combination of amivantamab and tepotinib can help to control NSCLC. The safety of this drug combination will also be studied.

开始日期2024-06-18

申办/合作机构

The University of Texas MD Anderson Cancer Center

NCT06106802 / Not yet recruiting临床2期IIT

Lazertinib and Tepotinib for EGFR Mutant NSCLC in MET Overexpressed or Amplified Who Progressed After Lazertinib Treatment: A Phase II Multi-center Trial

As the 3rd generation, EGFR TKI has become a standard treatment option for the 1st line therapy in EGFR mutated patients, the necessity for evaluating resistant mechanism to determine the matched subsequent therapeutic option has been highlighted. From the 1st line Osimertinib treatment, the heterogenous resistance mechanism has been observed showing most commonly by MET amplification (7-15%) followed by additional on-target EGFR mutation (6-10%), BRAF, PI3KCA, KRAS, HER2 mutation (13-14%) and still 40 to 50% remain unknown for the mechanism. (A. Leonetti et al.British Journal of Cancer(2019))
Based on the observation showing the MET amplification as the most common resistance mechanism to the 3rd generation EGFR TKI treatment, the "TATTON" study, a multi-arm, phase IB trial, demonstrated early clinical data of Osimertinib in combined with savolitinib. Among the patients, c-MET amplified patients who were previously treated with 3rd generation EGFR TKI, a combination of Osimertinib and savolitinib, showed an objective response rate of 33% and median PFS of 5.5 months. (G. Oxnard et al. Annals of Oncology(2020))
The clinical efficacy of Osimertinib with savolitinib in MET overexpressed or amplification patients are reported from the global phase II, "SAVANNAH" study. The preliminary results from the SAVANNAH trial showed that Osimertinib plus savolitinib demonstrated an objective response rate of 49% in patients with a high level of MET overexpression and/or amplification, defined as IHC90+ and/or FISH 10+, whose disease progressed on treatment with Osimertinib. The highest ORR was observed in patients with a high level of MET who were not treated with prior chemotherapy (52%). In patients whose tumors did not show a high level of MET, the ORR was 9% (MJ Ahn, WCLC, 2022). There are ongoing global Phase III SAFFRON study to validate the outcome from SAVANNAH study.
It has been reported that around 62% of tumor in Osimertinib progressed sample has MET overexpression and/or amplification, and more than one-third (34%) met the defined high MET level cut-off.
As Lazertinib is about to be approved as the treatment option for the treatment naïve EGFR mutated NSCLC, it is also becoming important to develop a further treatment plan based on the MET amplification status. In this study, the investigators designed a phase II study based on the MET amplification status to evaluate the clinical efficacy of Lazertinib + tepotinib.

开始日期2024-02-02

申办/合作机构

Samsung Medical Center

100 项与盐酸特泊替尼相关的临床结果

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100 项与盐酸特泊替尼相关的转化医学

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100 项与盐酸特泊替尼相关的专利（医药）

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170

项与盐酸特泊替尼相关的文献（医药）

2024-11-01·Thoracic Cancer

Remarkable pathological response to neoadjuvant tepotinib in lung adenocarcinoma with MET exon 14 skipping mutation: A case report

Article

作者: Zhong, Wei ; Liu, Xiaoyan ; Li, Rongzhen ; Zhao, Jing ; Wang, Mengzhao ; Xu, Yan ; Gao, Xiaoxing ; Chen, Minjiang

AbstractMesenchymal–epithelial transition (MET) exon 14 (METex14) skipping mutation is a rare (3%–4%) driver mutation in non‐small cell lung cancer (NSCLC). Tepotinib, a selective MET inhibitor, has shown promise in treating METex14 skipping‐mutated NSCLC. However, its feasibility for perioperative application remains unclear. This report describes a 60‐year‐old man with stage IIIA (cT2N2M0) lung adenocarcinoma harboring a METex14 skipping mutation. After initial treatment with savolitinib was discontinued due to grade 4 transaminitis, the patient was switched to tepotinib, resulting in significant tumor regression. Six months later, further shrinkage was observed, and surgery revealed remarkable pathological response with no residual tumor in lymph nodes (ypT2N0M0, IB). Postoperative tepotinib continued, with no relapse at 6‐month follow‐up. This case highlights the potential of tepotinib as neoadjuvant therapy for resectable METex14 skipping‐mutated NSCLC, warranting further clinical trials.

2024-11-01·Neoplasia

Spatial profiling of METex14-altered NSCLC under tepotinib treatment: Shifting the immunosuppressive landscape

Article

作者: Reischmann, Nadine ; Karachaliou, Niki ; Simard, Manon A ; Geist, Felix ; Cabrera-Galvez, Carlos ; Zühlsdorf, Michael ; Viteri, Santiago

MET inhibitors have demonstrated efficacy in treating patients with non-small cell lung cancer (NSCLC) harboring METex14 skipping alterations. Advancements in spatial profiling technologies have unveiled the complex dynamics of the tumor microenvironment (TME), a crucial factor in cancer progression and therapeutic response. This study uses spatial profiling to investigate the effects of the MET inhibitor tepotinib on the TME in a case of locally advanced NSCLC with a METex14 skipping alteration. A patient with resectable stage IIIB NSCLC, unresponsive to neoadjuvant platinum-based chemotherapy, received tepotinib following the detection of a METex14 skipping alteration. Paired pre- and post-treatment biopsies were subjected to GeoMx Digital Spatial Profiling using the Cancer Transcriptome Atlas and immune-related protein panels to evaluate shifts in the immune TME. Tepotinib administration allowed for a successful lobectomy and a pathological downstaging to stage IA1. The TME was transformed from an immunosuppressive to a more permissive state, with upregulation of antigen-presenting and pro-inflammatory immune cells. Moreover, a marked decrease in immune checkpoint molecules, including PD-L1, was noted. Spatial profiling identified discrete immune-enriched clusters, indicating the role of tepotinib in modulating immune cell trafficking and function. Tepotinib appears to remodel the immune TME in a patient with METex14 skipping NSCLC, possibly increasing responsiveness to immunotherapy. Our study supports the integration of genetic profiling into the management of early and locally advanced NSCLC to guide personalized, targeted interventions. These findings underscore the need to further evaluate combinations of MET inhibitors and immunotherapies.

2024-10-01·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 ; Bolleddula, Jayaprakasam ; Venkatakrishnan, Karthik ; Gao, Wei ; Klopp‐Schulze, Lena ; Strotmann, Rainer ; Lu, Hong ; Dong, Jennifer ; Li, Dandan ; Mukker, Jatinder Kaur ; Goteti, Kosalaram ; Terranova, Nadia

AbstractWith 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.

项与盐酸特泊替尼相关的新闻（医药）

2024-11-18

·Business Wire

U.S. Food and Drug Administration Approves FoundationOne®Liquid CDx as a Companion Diagnostic for TEPMETKO® (tepotinib) to Identify Patients with MET Exon 14 Skipping Alterations in Non-Small Cell Lung Cancer

BOSTON--( BUSINESS WIRE )-- Foundation Medicine, Inc. today announced that it has received approval from the U.S. Food and Drug Administration (FDA) for FoundationOne ® Liquid CDx to be used as a companion diagnostic for TEPMETKO ® (tepotinib) developed by EMD Serono, the healthcare business of Merck KGaA, Darmstadt, Germany in the U.S. and Canada. TEPMETKO received accelerated approval from the FDA in February 2021 and traditional approval in February 2024 for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition ( MET ) exon 14 skipping alterations ( MET ex14). 1 FoundationOne Liquid CDx is the first FDA-approved companion diagnostic to identify patients who may be eligible for TEPMETKO. NSCLC accounts for approximately 85% of lung cancers, 2 of which 3-4% are associated with MET ex14. 3 MET ex14 skipping alterations in patients have been associated with advanced disease and a poor prognosis. 4 “Access to a high-quality liquid biopsy, like FoundationOne Liquid CDx, can help unlock the power of precision medicine for more patients with non-small cell lung cancer,” said Mia Levy, M.D., Ph.D., chief medical officer at Foundation Medicine. “We’re proud that our liquid biopsy is the first companion diagnostic approved in the U.S. for TEPMETKO as it will help identify more patients with MET ex14 skipping alterations who may be appropriate for targeted treatment.” Foundation Medicine is the only company with an FDA-approved portfolio of tissue and blood-based comprehensive genomic profiling tests. From a routine blood sample, FoundationOne Liquid CDx analyzes more than 300 cancer-related genes to provide genomic insights. With today’s approval, Foundation Medicine has more than 19 FDA-approved companion diagnostic indications for NSCLC, the most of any company. 5 “Targeted therapies have led a revolution to how lung cancer is treated,” said GO2 for Lung Cancer President and CEO Laurie Ambrose. “Biomarker testing plays a crucial part in getting these treatments into the hands of patients. We’re excited to see that patients with advanced NSCLC have more access to treatment options because of non-invasive liquid biopsies.” Foundation Medicine is the global leader in approved companion diagnostic indications, with 50% of all approved companion diagnostic indications for next-generation sequencing (NGS) testing in the United States and Japan. 6 Foundation Medicine ® and FoundationOne ® are registered trademarks of Foundation Medicine, Inc. About Foundation Medicine: Your Essential Partner in Cancer Care Foundation Medicine is a pioneer in molecular profiling for cancer, working to shape the future of clinical care and research. We collaborate with a broad range of partners across the cancer community and strive to set the standard for quality, scientific excellence, and regulatory leadership. Our deep understanding of cancer biology helps physicians make informed treatment decisions for their patients and empowers researchers to develop new medicines. Every day, we are driven to help our partners find answers and take action, enabling more people around the world to benefit from precision cancer care. For more information, please visit us on www.FoundationMedicine.com and follow us on LinkedIn and X . About FoundationOne ® Liquid CDx FoundationOne ® Liquid CDx is a qualitative next generation sequencing based in vitro diagnostic test for prescription use only that uses targeted high throughput hybridization-based capture technology to analyze 324 genes utilizing circulating cell-free DNA (cfDNA) isolated from plasma derived from anti-coagulated peripheral whole blood of advanced cancer patients. The test is FDA-approved to report short variants in over 300 genes and is a companion diagnostic to identify patients who may benefit from treatment with specific therapies (listed in Table 1 of the Intended Use) in accordance with the approved therapeutic product labeling. Additional genomic findings may be reported and are not prescriptive or conclusive for labeled use of any specific therapeutic product. Use of the test does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Patients who are negative for companion diagnostic mutations should be reflexed to tumor tissue testing and genomic alteration status confirmed using an FDA-approved tumor tissue test, if feasible. For the complete label, including companion diagnostic indications and complete risk information, please visit www.F1LCDxLabel.com . ____________________ 1 TEPMETKO. Prescribing Information. EMD Serono; 2024. Accessed May 24, 2024. https://www.emdserono.com/us-en/pi/tepmetko-pi.pdf 2 American Cancer Society. Key Statistics for Lung Cancer. Updated January 29, 2024. Accessed May 22, 2024. https://www.cancer.org/cancer/types/lung-cancer/about/what-is.html 3 The Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature . 2014;511:543-550. https://doi.org/10.1038/nature13385 4 Awad MM, Leonardi GC, Kravets S, et al. Impact of MET inhibitors on survival among patients with non-small cell lung cancer harboring MET exon 14 mutations: a retrospective analysis. Lung Cancer . 2019;133:96-102. https://doi.org/10.1016/j.lungcan.2019.05.011 5 Data on File, Foundation Medicine, Inc. 2024 6 Data on File, Foundation Medicine, Inc. 2024

上市批准

2024-11-01

·凯莱英药闻

本周新药里程碑汇总：16款国产新药申请IND，包括首个环状RNA

欢迎关注凯莱英药闻（收集周期：10.28-11.1，国内部分为首次申请临床、首次批准上市的创新药）国内创新药IND汇总 1、益承康泰：伊匹乌肽雾化吸入溶液作用机制：p55PIK抑制剂适应症：消炎药 10月28日，益承康泰的伊匹乌肽雾化吸入溶液的临床试验申请（IND）获CDE受理。伊匹乌肽（Epivotide）是公司自主研发的一种高选择性p55PIK抑制剂，具有广谱抗炎功效，对人体的毒副作用非常小。p55PIK是磷脂酰肌醇3-激酶（PI3K）的一种亚型，PI3K信号通路在调节细胞生长、运动、存活、代谢和血管生成过程中起着重要作用。研究发现，由于深度参与了炎症过程（血管通透性，炎症参与细胞增殖，炎症细胞趋化和浸润），PI3K信号通路的过度活跃与多种炎症和自身免疫性疾病的发生和进展有显著的相关性。 2、莱恩医药：1D228片作用机制：c-Met/Trk抑制剂适应症：癌症 10月28日，莱恩医药的1D228片的IND获CDE受理。1D228是一款靶向c-Met和TRK的新型激酶抑制剂，可同时靶向肿瘤细胞和血管内皮细胞，表现出优异的抗肿瘤活性。体外模型实验发现，1D228对癌细胞增殖和迁移的抑制作用明显优于阳性药物tepotinib，可显著抑制体内c-Met和TRK原癌基因（TRKB）双表达肿瘤的肿瘤生长。此外，体内实验胃癌（MKN45细胞系）和肝癌（MHCC97H细胞系）肿瘤模型中，1D228都表现出显著的肿瘤抑制作用。重要的是，与tepotinib治疗相比，在MHCC97H和MKN45异种移植肿瘤模型中，1D228治疗显示出更强的抗肿瘤活性和更低的毒性。 3、欧科健生物：OCUL101注射液作用机制：靶向C5/VEGFR双抗适应症：脉络膜新生血管 10月30日，欧科健生物的OCUL101注射液的IND获CDE受理。OCUL101是一款靶向C5/VEGFR的双抗，不仅能够有效稳定和控制血管增生，减少视网膜血管末端的渗漏，且疗效不仅限于对VEGF抗体治疗敏感的患者，更有望惠及对VEGF抗体治疗无效的nAMD患者。一项评估眼内注射(IVT) OCUL101治疗续性视网膜新生血管化(PRNV或DL-AAA)兔模型中的疗效研究显示，所有治疗组的PRNV模型眼在治疗后两周内均观察到PRNV部位无血管造影泄漏现象。在荧光血管造影(FA)分析中，与安慰剂相比，OCUL101对PRNV泄漏的抑制效果在持续时间和强度上均有所差异。阳性对照组(PC组)的泄漏复发主要发生在治疗后约6~8周，而OCUL101组则延迟约12~16周。 4、环码生物：HM2002注射液作用机制：—— 适应症：缺血性心脏病 10月30日，环码生物的HM2002注射液的IND获CDE受理。HM2002是一种创新环形RNA（circRNA）药物，用于治疗性血管再生，以治疗缺血性心脏病。临床前研究显示，在心肌梗死动物模型中，HM2002注射液能够促进血管再生，减少梗死和纤维化面积，显著改善心功能。 5、MedRegen：MRG-001注射液作用机制：CXCR4拮抗剂；CaN/FKBP12分子胶适应症：免疫调节和组织再生疗法 10月31日，MedRegen的MRG-001注射液的IND获CDE受理。MRG-001是普乐沙福与他克莫司形成的复方制剂，临床前研究表明，MRG-001可以改善伤口愈合，促进组织再生，防止同种异体移植排斥反应。一项I期试验显示，MRG-001在选定剂量范围内是安全的，没有明显的实验室异常；中剂量组对白细胞、干细胞和免疫调节细胞的作用最显著。 6、派金生物：PJ008注射液作用机制：—— 适应症：苯丙酮尿症 10月31日，派金生物的PJ008注射液的IND获CDE受理。PJ008通过MAS-PEG平台的专有基因改造，再经定向聚乙二醇修饰得到PL5。目前，该药物已完成结构筛选，通过体内评价；研究显示该药物具有低免疫原性、可实现每周一次皮下给药。 7、柯君医药：苯磺酸CG-0255胶囊作用机制：P2Y12受体拮抗剂适应症：血栓 11月1日，柯君医药的苯磺酸CG-0255胶囊的IND获CDE受理。CG-0255是新型抗血小板药物，是基于氯吡格雷活性成分设计的世界第一个巯基前药，也是世界上第一个既可以口服，也可以静脉注射的P2Y12抑制剂。CG-0255创新性地通过羧酸酯酶转化生成活性代谢产物 H4，这与氯吡格雷通过 CYP 酶转化生成的活性代谢产物 H4 相同。此外，CG-0255 无需通过 CYP 酶发挥抗血小板作用，有望使得存在 CYP 酶功能缺失的广大患者受益。一项在健康受试者中评估其安全性和耐受性，以及药物代谢动力学和药效学的数据显示：（1）CG-0255药物的个体差异性低于氯吡格雷，其中注射剂型起效时间小于15分钟，口服剂型起效时间小于30分钟。（2）口服剂型2 mg低剂量组血小板聚集抑制率约40%，和氯吡格雷300 mg组药效相当。注射和口服剂型的剂量-药效关系都比较明确。（3）CG-0255不经过CYP代谢，减少了药物之间的相互作用；可以和其他经CYP代谢的药物安全联用。（4）注射剂型可以一次推注给药，不需要持续滴注，且药效持续超过一天。 8、诺华：PIT565注射液作用机制：靶向CD3/CD2/CD19三抗适应症：肿瘤、自身免疫性疾病 11月1日，诺华的PIT565注射液的IND获CDE受理。PIT565是一款靶向CD3/CD2/CD19三抗药物，具有潜在同类首创的作用机制，目前正开发用于包括B细胞急性淋巴细胞白血病、B细胞淋巴瘤、系统性红斑狼疮、非霍奇金淋巴瘤在内的多个适应症。与 CD3 双特异性抗体相比，通过 PIT565 进行的 CD2 共刺激可以克服 T 细胞耗竭并增加患者的反应深度和持续时间；研究显示：（1）在采用 CD19+ 肿瘤细胞和原代T细胞共培养的重定向 T 细胞细胞毒性 (RTCC) 体外试验中，与对照双特异性产品相比，PIT565 在肿瘤细胞杀伤和增殖中介导更持久的 T 细胞活性。（2）在人外周血单核细胞过继转移模型中，PIT565 在已建立的弥漫性大 B 细胞淋巴瘤肿瘤模型中，表现出比对照双特异性产品更强的抗肿瘤反应。（3）在安全性和药理学研究中，PIT565 在食蟹猴中表现出 IgG 样药代动力学和与 CD3 双特异性产品相似的预期药理学和耐受性特征。国内创新药上市获批 1、葛蓝新通：甲磺酸普雷福韦片作用机制：核苷类似物适应症：乙型肝炎 10月28日，葛蓝新通的甲磺酸普雷福韦片的上市申请获得NMPA批准，用于治疗成人慢性乙型肝炎。甲磺酸普雷福韦（甲磺酸帕拉德福韦）是一款采用HepDirectTM前药技术开发的阿德福韦（PMEA）的前药。该药在血液及非靶器官稳定，使其代谢产物的组织暴露量低；口服进入靶器官肝脏后释放活性代谢产物，提高了抗病毒效率，抗耐药性也更强，同时还解决了阿德福韦酯肾毒性大的问题。III期临床试验与富马酸替诺福韦二吡呋酯（TDF）头对头比较研究显示，其结果达到预期，各项疗效指标与对照组一致或好于对照，尤其对高病毒载量病人的应答率治疗组中的疗效更为突出。 2、礼来：匹妥布替尼片作用机制：BTK 抑制剂适应症：套细胞淋巴瘤 10月29日，礼来的匹妥布替尼片的上市申请获得NMPA批准，用于既往接受过布鲁顿氏酪氨酸激酶（BTK）抑制剂治疗的复发或难治性套细胞淋巴瘤（MCL）成人患者。匹妥布替尼（pirtobrutinib）是一款非共价、具高度选择性的BTK抑制剂，是获FDA批准的首个非共价（可逆转）BTK抑制剂，同时也是首个获批用以治疗已对BTK共价抑制剂产生抗性的MCL患者的BTK抑制剂。与前两代BTK共价抑制剂不同，pirtobrutinib与C481没有直接的相互作用，对BTK的选择性更高，可减少治疗产生的不良事件，有望解决前两代BTK抑制剂耐药问题。研究显示，在MCL患者中，接pirtobrutinib治疗患者的总缓解率为50%，分别有13%与38%的患者达到了完全缓解和部分缓解，中位缓解时间为1.8个月(0.8-4.2)，中位缓解持续时间为8.3个月，6个月DOR率为65.3%。全球新药III期临床汇总感谢关注、转发，转载授权、加行业交流群，请加管理员微信号“hxsjjf1618”。 “在看”点一下

临床申请

2024-11-01

·药智网

2024医保谈判收官，创新药企的最关键一年

2024年医保谈判，比往年提前了一点，赶在了最冷的时节到来之前。全国人大会议中心的门口反而没有像往年那样人头攒动。场外陪同的企业人士格外的少，谈判代表进场后，他们站在商务车附近，分散在全国人大中心街道上和附近的胡同里，随时准备接应从会场出来的谈判代表。今年谈判代表依然三缄其口，从现场出来后三两步走到车上，扬长而去。除了谈判企业，还有前来了解风向的其他投资方和企业方人士。一位药企人士在场外驻足一会，本想跟同行聊一聊，但来的时间不巧，没遇到熟人。他今年没参与谈判，是为了明年做准备，“今年预示明年，如果今年严峻，明年只会更严峻。” 01 没有灵魂砍价，但依然艰巨的谈判从谈判企业来看，第一天谈判品种主要是代谢、心血管、镇痛等，第二天主要是降糖药和肿瘤药，第三天以肿瘤药和中药为主，最后一天多为非独家竞价品种。从场外很难看出总体风向，无法用温和或者严峻的词汇一概而论，所有情况都因品种而论。 PD-1格局或许有变，目录外的PD-1中，誉衡生物的赛帕利单抗、正大天晴/康方生物的派安普利单抗去年放弃谈判资格，今年是首次参与。恒瑞、君实和百济神州也要进行新增适应症谈判。糖尿病药物和肺癌药物依然竞争激烈。糖尿病药物品种多，专家过评率较高，主打一个混战。今年诺和诺德公司的依柯胰岛素周制剂，海思科的DPP-4抑制剂考格列汀片，信立泰的DPP-4抑制剂福格列汀、恒瑞的（SGLT2）抑制剂脯氨酸加格列净片、复方制剂恒格列净二甲双胍缓释片、武汉久安药物研究院的盐酸二甲双胍缓释片均前来谈判。肺癌领域按照靶点分成不同赛场。三代EGFR迎来新的搅局者，今年上市的圣和药业的瑞厄替尼片、倍而达的瑞齐替尼现身。MET抑制剂中三个特泊替尼（默克）、卡马替尼（诺华）、伯瑞替尼（鞍石生物）都出现在初审名单中。ROS1抑制剂方面，今年获批的瑞普替尼（再鼎医药）、安奈克替尼（正大天晴）在初审名单中，即将冲击两款进口药克唑替尼（辉瑞）、恩曲替尼（罗氏）的市场地位。大多数领域内资和外资已经在正面交锋，自免领域目前还是外资的主场，涉及的自免药物包括赛诺菲的度普利尤单抗、GSK的IL-5生物制剂美泊利珠单抗、诺华的司库奇尤单抗、辉瑞的JAK抑制剂阿布昔替尼。有的品种谈判时间不到半小时，康方生物的两款双抗产品和阿斯利康的DS-8201都在第二天上午进行谈判，他们结束得尤其的晚，康方生物董事长夏瑜下午一点才走出会场，比她更晚的还有阿斯利康中国区副总裁黄彬。一周前的预谈判会有更多拉锯。在专家评审阶段结束后，国家医保局会通过申报系统向相关企业反馈评审结果，包括经专家评审确定的谈判/竞价参照药品、谈判主规格和医保支付范围等内容。在预谈判阶段，药企可以了解到参照药品的选择。如果对参照药品的选择不满意，还有机会进行申诉的。药企对正式谈判的预期反而是比较明确的。但偶尔会出现意外插曲，现场因素也有可能对结果产生影响。一位企业代表听说同品种竞品已经完成续约，顿时紧张起来，该竞品是他们的参照药品，他担心竞品再次降价后，压缩了自己谈判的空间。不管客观情况如此，药企的主要任务就是证明自己值得被最大的支付方医保买单。业内人士对于谈判产品的最终成功率倒是有比较乐观的期待。“经过多年的谈判经验后，谈判双方更有默契，对于降价幅度、信封底价也有把握。” 值得关注的是，今年很少看到对灵魂砍价的宣传，在国家医保局官方公众号的评论区，精选留言中许多关于对创新药进医保的呼声。图片来源：深蓝观 02 什么是有价值的创新？今年医保谈判的特点之一，在于谈判品种较少，前期评审时的过评率较低。2023年国家医保谈判，121个品种谈判成功；而今年，通过形式审查的目录外药品249种，最终参加谈判或竞价的只有117种。一名医保研究者说到：“国谈现在主要是医保资金池子有限。降幅和通过率也都降低了不少。”根据医保局在谈判开始前发布的一系列文件，本次国谈以“加快创新药的临床应用”为重点，将主要关注创新护城河高的产品，对于普通品种的药物较往年而言筛选更严格。业内流传，今年医保局的一个重要任务是：支持创新药。国家医保局已经建立起一套在流程上科学、系统的医保准入程序，包括准备阶段、申报阶段、专家评审、谈判/竞价与结果公布，其中专家评审是实现“价值定价”的核心，包含综合评审与药品价格测算两大关键价值评估环节。从去年开始,医保部门在药物评审中新引入了药品分类方法,基于临床价值分为突破性疗法、改良型新药、药效相当、不及性药物4种。不及性药物指的是那些疗效不显著优于现有药物、毒副作用不更低、患者依从性不更佳的药物，这类药品在医保评审中不被视为优先考虑的对象。医保局格外强调对创新药的鼓励，但对于创新药的分类和出价，药企或许会有不同意见。这一偏差体现在医保局对参照药品的选择上，比如用一代药作为二代药的参照，用不同适应症的同类药作为参照。药企如果不满意参照药品的选择，可以进行申诉，但有说服力的理由不应该只是技术的迭代，而是真正的临床价值。从这个角度来看，今年有很多有讨论空间的品种。比如恒瑞的复方制剂恒格列净二甲双胍缓释片，是首个SGLT2抑制剂联合二甲双胍的固定复方缓释制剂，在疗效上提供了血糖控制和额外的心血管保护效果，最终能在价格上可能高于普通二甲双胍。康方的两款PD-1双抗，是相对于PD-1单抗的升级。目前医保目录内的四款PD-1单抗年治疗费用已经很低，按照用药时间12个月测算，恒瑞医药卡瑞利珠单抗年治疗费用约4.6万元、百济神州替雷利珠单抗年治疗费用约4.5万元、君实生物特瑞普利单抗年治疗费用约4.4万元. 康方生物在谈判前将卡度尼利单价从13220元/125mg/瓶降至6166元/125mg/瓶，降幅为53.4%，年治疗费用控制在20万元以下。依沃西单抗保持49.7万的年治疗费用。 HER2 ADC方面，阿斯利康的三代ADC德曲妥珠单抗的HER2阳性乳腺癌二线治疗、HER2低表达乳腺癌二线预计本次谈判，由之前的8860元/支降为6912元/支，并同步取消慈善赠药，年治疗费用依然在30万以上。其参照药是同为HER-2靶点的ADC药物注射用恩美曲单抗，罗氏的二代ADC恩美曲妥珠单抗目前共获批HER2阳性乳腺癌二线和辅助治疗2个适应症，已在医保目录中，预计今年到期续约。恩美曲妥珠单抗年用药费用为13.44万元，两者中间还有十多万的价格gap。医保局对这些升级换代药物的价值评定，要等到谈判结果出来之后才能揭晓。 03 最关键的一年从2015年开始，中国创新药行业经历了10年的研发阶段，现在正迎来自主创新药的收获阶段，走完第一个产业周期。药企到了关键时期，如果销售额无法覆盖研发投入，看不到商业化的希望，药企会早早将临床早期的管线以几千万美元的首付款授权给海外药企。近两年，海外BD“不得已的活跃”，成为药企的生存手段。能BD出海的管线，一定是存在国际竞争力的。这些管线在临床早期就被海外药企锁定，可能会减少国内企业从这些研发投入中获得的回报。由此会给整个产业链带来一个难题：前期投入的社会融资、政府引导基金、政府补贴就会代为补偿。这样损失的不仅是在第一个产业周期的投入，还有对下一个产业周期的预期。近几年里，今年尤为关键。从营收环境来看，今年转好希望有限。根据各企业中报，2024年上半年，医药板块的营业收入为1.3万亿元，较去年同期略有下降，降幅为0.44%。从投资规模来看，上半年医疗健康领域一级市场共发生630起投融资事件，同比下降27.8%，融资金额总计421.6亿人民币，同比下降1.1%。在生物制药融资寒冬之际，如果中国生物技术公司因为资金不足，将有潜力的药物授权给跨国药企来继续开发，那么这些药物最终由跨国公司上市，这会使医保谈判更难，因为跨国公司对药品价格的要求通常更高。在外界环境掣肘的条件下，此次产品是否能够进入医保目录，将影响着药企在未来一段时间的走向。但上述医保研究者也提到，这种“指望”本身是不平衡、不健康的，尤其在定价方面，医保方和企业方的逻辑是不同的。 “从研发，立项，临床，投资融资，等等环节，把创新药的未来市场预期和企业估值拉到一个脱离市场的水平。然后遇到了一个目前筹资只有一年3万亿左右不到的医保，中国药品行业市场营销就是不到一万亿的市场规模。之前有个专家做过统计，医保基金3万亿，换算成美元，仅仅跟全球最大的两家药企年营收持平。”上述研究者分析到。” 在我国医疗支付端结构以单一的医保基金支付为主的现状下，医保基金任务艰巨。在这种情况下，想要把投资方、产品方、支付方的期待拉平，一方面要对医保基金进行结构性调整。数据显示，2022年，医保对新药的支出从2019年的59.49亿元增长到481.89亿元，增长了7.1倍。浙商证券计算，2022年创新药占医保基金比例仅为1.96%。1.96%的占比说明医保基金对创新药支付的提升空间仍然很大，应该是医药板块少有的医保支出金额具有较大上行空间的行业（2017年美国医药市场创新药占比77%，中国创新药占比仍较低）。腾笼换鸟，涉及利益博弈，需要魄力和时间。另一方面要依靠市场上更多参与方的加入和稀释。这也是国家医保部门在谈判之外正在积极谋划的事务——构建多层次的保障体系。近期，上海医保局率先开始了多元支付的试点行动，参与方包括两家商保公司，12家公立医院，以及上海医保局、上海金融监管局、上海保交所等官方部门。患者在就诊后，可以即时享受“商保+医保”的一次性结算。同时，今年9月，国务院印发《关于加强监管防范风险推动保险业高质量发展的若干意见》，其中提到：推动商业健康保险与健康管理深度融合。鼓励面向老年人、慢病患者等群体提供保险产品。 “医保是保基本的前提下支持创新。其他资本可以在鼓励创新前提下兼顾基本。”上述医保研究者说到。在他看来，无论每年的谈判降幅如何浮动，最终落入的价格区间必定是在医保视野下的合理价格，为基本保障的目的而设置，只能兼顾鼓励创新。因此，讨论降幅变化的意义不大，只有将以鼓励创新为主要目的的市场化支付逻辑重新整合，中国创新药企业才能真正找到一条长久稳定的道路。来源 | 深蓝观（药智网获取授权转载）撰稿 | 吴妮李昀责任编辑 | 八角声明：本文系药智网转载内容，图片、文字版权归原作者所有，转载目的在于传递更多信息，并不代表本平台观点。如涉及作品内容、版权和其它问题，请在本平台留言，我们将在第一时间删除。商务合作 | 王存星 19922864877（同微信）阅读原文，是受欢迎的文章哦

100 项与盐酸特泊替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	L01XE	DB15133

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
MET外显子14跳变的非小细胞肺癌	韩国	Merck & Co., Inc.	2021-11-23
非小细胞肺癌	日本	Merck KGaA	2020-03-25

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
非小细胞肺癌	临床2期	奥地利	Merck KGaA	2016-07-14
非小细胞肺癌	临床2期	波兰	Merck KGaA	2016-07-14
非小细胞肺癌	临床2期	比利时	Merck KGaA	2016-07-14
非小细胞肺癌	临床2期	德国	Merck KGaA	2016-07-14
非小细胞肺癌	临床2期	西班牙	Merck KGaA	2016-07-14
非小细胞肺癌	临床2期	韩国	Merck KGaA	2016-07-14
非小细胞肺癌	临床2期	法国	Merck KGaA	2016-07-14
晚期肝细胞癌	药物发现	韩国	Merck KGaA	2014-01-06
晚期肝细胞癌	药物发现	中国台湾	Merck KGaA	2014-01-06
晚期肝细胞癌	药物发现	中国	Merck KGaA	2014-01-06

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临床结果

适应症

分期

评价

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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


NCT03940703 (INSIGHT 2, Pubmed) 人工标引	临床2期	非小细胞肺癌二线 \|	128	Tepotinib plus osimertinib (progression on first-line osimertinib)	(鑰製艱製選夢製簾簾壓) = 築憲鑰簾夢蓋鑰築簾蓋憲襯糧膚顧顧觸獵壓鹹 (窪鹹醖顧憲觸糧廠觸鬱, 39.7 ~ 60.3) 更多	积极	2024-08-25
NCT03546608 (CTgov)	临床1期	肝功能不全	18	Tepotinib (Healthy Participants (Control))	繭壓鹽壓淵鏇廠齋網製(齋夢鏇築遞繭齋製積鹹) = 選鏇鏇鑰選鏇鏇膚艱衊鹽鹽願齋構遞積鹹夢夢 (憲廠膚衊醖築築範築襯, 鹹網鏇糧鏇願製積糧糧 ~ 製範糧製築膚顧願願淵) 更多	-	2024-08-12
				Tepotinib (Mild Hepatic Impairment (Child-Pugh Class A))	繭壓鹽壓淵鏇廠齋網製(齋夢鏇築遞繭齋製積鹹) = 壓構壓淵餘顧鏇鑰顧鬱鹽鹽願齋構遞積鹹夢夢 (憲廠膚衊醖築築範築襯, 構築鏇糧構鏇顧窪遞襯 ~ 艱鏇網範襯廠願構齋蓋) 更多
NCT02864992 (VISION, ASCO2024) 人工标引	临床2期	非小细胞肺癌	248	tepotinib (Brain metastases)	(繭廠糧築鬱願憲鹽鹽鏇) = 醖簾製蓋構艱淵夢襯製構鏇廠窪夢網齋願鬱鹹 (構選觸衊齋餘積選範憲, 2.41) 更多	积极	2024-05-24
				tepotinib (Liver metastases)	(繭廠糧築鬱願憲鹽鹽鏇) = 鏇範願齋製衊繭繭衊憲構鏇廠窪夢網齋願鬱鹹 (構選觸衊齋餘積選範憲, 2.27) 更多
NCT04647838 (KCSG AL19-17, ASCO2024)	临床2期	实体瘤 \| 肿瘤转移 ctDNA \| METex14 \| METamplification ... 更多	35	Tepotinib	(膚淵範鑰獵選鑰築獵遞) = 淵觸鏇製鏇獵構膚積構鹽襯廠構糧膚餘憲蓋簾 (網繭顧鹹鏇顧簾艱鹹鏇 ) 更多	积极	2024-05-24
				Placebo	(膚淵範鑰獵選鑰築獵遞) = 鬱積繭醖蓋簾顧遞鏇遞鹽襯廠構糧膚餘憲蓋簾 (網繭顧鹹鏇顧簾艱鹹鏇 ) 更多
NCT02864992 (VISION, Pubmed)	临床2期	MET外显子14跳变的非小细胞肺癌	106	tepotinib 500 mg	(壓鑰遞衊窪艱醖艱襯淵) = 餘醖網醖範製醖獵積製鏇顧餘壓蓋選鑰選鬱顧 (選構糧廠築觸窪膚網艱 ) 更多	积极	2024-04-04
NCT05213481 (CTgov)	临床1期	-	18	Carbamazepine+Tepotinib	蓋製廠襯襯遞壓夢鹹築(蓋膚淵艱構築醖餘獵顧) = 鹽餘憲膚鬱遞餘範顧選鹹襯蓋壓窪鑰壓獵襯醖 (願築製願觸夢窪鹹選齋, 簾繭繭齋鏇獵構願觸獵 ~ 觸夢選選簾範廠膚鹽製) 更多	-	2024-03-08
NCT05203822 (CTgov)	临床1期	-	18	Tepotinib (Tepotinib)	齋簾糧壓鏇糧鬱繭觸糧(選蓋製醖淵鹹願鏇鏇製) = 壓淵獵餘簾願積願膚淵夢簾築憲醖壓顧壓繭鬱 (廠壓鏇衊艱齋顧簾鑰夢, 鬱構蓋鬱窪範顧遞憲夢 ~ 糧網壓願膚餘憲衊蓋蓋) 更多	-	2024-02-20
				Itraconazole+Tepotinib (Tepotinib and Itraconazole)	齋簾糧壓鏇糧鬱繭觸糧(選蓋製醖淵鹹願鏇鏇製) = 獵鏇遞網廠淵繭壓襯範夢簾築憲醖壓顧壓繭鬱 (廠壓鏇衊艱齋顧簾鑰夢, 鹹糧窪鏇鬱鹽蓋艱壓積 ~ 糧窪糧餘廠夢齋選糧製) 更多
NCT04204902 (CTgov)	临床1期	-	18	Tepotinib (Tepotinib Test Treatment)	廠餘窪醖遞鏇鹹夢鬱簾(糧艱淵繭鬱顧構廠衊築) = 範艱廠鹹夢網獵鏇艱鹹蓋積餘醖醖獵衊壓餘壓 (衊鏇窪積獵構窪鬱選窪, 餘糧膚築壓壓餘蓋積鹹 ~ 範鹹壓膚膚繭襯範膚襯) 更多	-	2023-11-08
				Tepotinib (Tepotinib Reference Treatment)	廠餘窪醖遞鏇鹹夢鬱簾(糧艱淵繭鬱顧構廠衊築) = 餘選鬱餘糧蓋遞艱醖遞蓋積餘醖醖獵衊壓餘壓 (衊鏇窪積獵構窪鬱選窪, 襯齋襯鏇鹽餘範廠願鏇 ~ 簾衊夢蓋餘壓鹹醖繭簾) 更多
NCT02864992 (VISION Cohort B, Pubmed \| Cell Rep Med)	临床2期	MET基因扩增非小细胞肺癌 METamp \| RB1 \| MYC ... 更多	24	Tepotinib	(獵糧鏇壓獵膚範鹽鏇鑰) = 膚醖簾積選艱獵選選蓋襯膚襯觸夢醖廠範鏇齋 (鑰積網衊壓遞糧範鹽淵, 22.1 ~ 63.4) 更多	积极	2023-11-01
NCT02864992 (VISION, ESMO2023) 人工标引	临床2期	晚期非小细胞肺癌	313	tepotinib (Treatment-naive; T+/L–)	(鬱顧憲壓膚襯簾網醖鑰) = 鏇廠餘淵築製餘蓋糧鹽廠簾醖積獵餘構壓艱觸 (製願構繭簾構鏇衊衊廠, 43.2 ~ 71.3) 更多	积极	2023-10-23
				tepotinib (Treatment-naive; T+/L+)	(鬱顧憲壓膚襯簾網醖鑰) = 遞膚窪願鹹遞醖膚窪齋廠簾醖積獵餘構壓艱觸 (製願構繭簾構鏇衊衊廠, 48.0 ~ 78.4) 更多