更新于：2024-07-01

Nintedanib esylate

乙磺酸尼达尼布

更新于：2024-07-01

概要

概要

基本信息

药物类型

小分子化药

别名

CYNEDIV、Intedanib、methyl (3Z)-3-[(4-{methyl[(4-methylpiperazin-1-yl)acetyl]amino}anilino)(phenyl)methylidene]-2-oxo-2,3-dihydro-1H-indole-6-carboxylate

+ [18]

靶点

CSF-1R x FGFRs x FLT3 x PDGFR x VEGFR

作用机制

CSF-1R拮抗剂(集落刺激因子1受体拮抗剂)、FGFRs拮抗剂(成纤维细胞生长因子受体家族拮抗剂)、FLT3抑制剂(酪氨酸蛋白激酶受体FLT3抑制剂)

治疗领域

肿瘤呼吸系统疾病皮肤和肌肉骨骼疾病+ [6]

在研适应症

进行性肺纤维化间质性肺疾病系统性硬皮病+ [20]

非在研适应症

大肠腺癌晚期结直肠腺癌晚期肝细胞癌+ [55]

原研机构

Boehringer Ingelheim International GmbH

在研机构

National Cancer Institute

Woodstock Sterile Solutions

美莱普（北京）医药研究有限公司

+ [10]

非在研机构

Blade Therapeutics, Inc.

Avalyn Pharma, Inc.

Martin-Luther-Universität Halle-Wittenberg

+ [2]

最高研发阶段批准上市

首次获批日期

美国 (2014-10-15),

特发性肺纤维化

最高研发阶段(中国)批准上市

特殊审评突破性疗法 (美国)、快速通道 (美国)、孤儿药 (美国)、优先审评 (中国)、特殊审批 (中国)、孤儿药 (日本)、孤儿药 (澳大利亚)

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结构

分子式C33H39N5O7S

InChIKeyMMMVNAGRWOJNMW-FJBFXRHMSA-N

CAS号656247-18-6

关联

284

项与乙磺酸尼达尼布相关的临床试验

NCT06297096 / Not yet recruiting临床3期IIT

Multicentre Clinical Trial Evaluating the Safety and Efficacy of the Combination of Nintedanib+Tocilizumab Compared to Standard Treatment in Patients With Systemic Sclerosis and Interstitial Lung Disease. Analysis With Theranostic Approach

The study includes adult patients with systemic sclerosis (SSc) with interstitial lung disease (ILD) to evaluate the efficacy and safety of nintedanib plus tocilizumab combination therapy compared to standard therapy (methotrexate, mycophenolate mofetil) for 56 weeks.

开始日期2024-04-01

申办/合作机构

Medical Research Agency

CTR20233766 / CompletedN/A

评估乙磺酸尼达尼布软胶囊150 mg和Ofev®（乙磺酸尼达尼布软胶囊）150 mg在健康成年男性受试者餐后状态下的生物等效性研究。

研究餐后状态下单次口服受试制剂乙磺酸尼达尼布软胶囊（规格：150 mg）与参比制剂乙磺酸尼达尼布软胶囊（Ofev®，规格：150 mg）在健康受试者体内的药代动力学，评价餐后状态口服两种制剂的生物等效性和安全性。

开始日期2024-02-23

申办/合作机构

齐鲁制药有限公司

CTR20232598 / Recruiting临床3期

一项多中心、双盲、随机、安慰剂对照的 12 个月（包括 12 个月的双盲延长）平行比较0.1%和0.2%CBT-001 与安慰剂（每日给药两次）治疗翼状胬肉患者的安全性和有效性的研究

评估 0.1%和 0.2%的 CBT-001 乳液每天给药两次在24 个月内与安慰剂相比在减少结膜充血和防止翼状胬肉进展方面的安全性和有效性。

开始日期2024-01-31

申办/合作机构

拨康视云生物医药科技（广州）有限公司

[+2]

100 项与乙磺酸尼达尼布相关的临床结果

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100 项与乙磺酸尼达尼布相关的转化医学

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100 项与乙磺酸尼达尼布相关的专利（医药）

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1,599

项与乙磺酸尼达尼布相关的文献（医药）

2024-12-31·Journal of enzyme inhibition and medicinal chemistry

Searching for novel MDM2/MDMX dual inhibitors through a drug repurposing approach

Article

作者: Wen, Hongmei ; Li, Wei ; Hu, Wenshu ; Li, Keting ; Liu, Jian ; Chen, Wenxing ; Wang, Yingjie ; Wang, Bo

Disruption of p53-MDM2/MDMX interaction by smaller inhibitors is a promising therapeutic intervention gaining tremendous interest. However, no MDM2/MDMX inhibitors have been marketed so far. Drug repurposing is a validated, practical approach to drug discovery. In this regard, we employed structure-based virtual screening in a reservoir of marketed drugs and identified nintedanib as a new MDM2/MDMX dual inhibitor. The computational structure analysis and biochemical experiments uncover that nintedanib binds MDM2/MDMX similarly to RO2443, a dual MDM2/MDMX inhibitor. Furthermore, the mechanistic study reveals that nintedanib disrupts the physical interaction of p53-MDM2/MDMX, enabling the transcriptional activation of p53 and the subsequent cell cycle arrest and growth inhibition in p53^+/+ cancer cells. Lastly, structural minimisation of nintedanib yields H3 with the equivalent potency. In summary, this work provides a solid foundation for reshaping nintedanib as a valuable lead compound for the further design of MDM2/MDMX dual inhibitors.

2024-05-01·The Journal of pharmacology and experimental therapeutics

Paclitaxel Aggravating Radiation-Induced Pulmonary Fibrosis Is Associated with the Down-Regulation of the Negative Regulatory Function of Spry2

Article

作者: Huang, Yihao ; Chen, Chun ; Zheng, Jianxing ; Xie, Lingfeng ; Hong, Jinsheng ; Wu, Jiandong

Paclitaxel (PTX) is capable of aggravating radiation-induced pulmonary fibrosis (RIPF), but the mechanism is unknown. Spry2 is a negative regulator of receptor tyrosine kinase-related Ras/Raf/extracellular signal regulated kinase (ERK) pathway. This experiment was aimed at exploring whether the aggravation of RIPF by PTX is related to Spry2. The RIPF model was established with C57BL/6 mice by thoracic irradiation, and PTX was administered concurrently. Western blot was used to detect the expression level of ERK signaling molecules and the distribution of Spry2 in the plasma membrane/cytoplasm. Co-immunoprecipitation (co-IP) and immunofluorescence were used to observe the colocalization of Spry2 with the plasma membrane and tubulin. The results showed that PTX-concurrent radiotherapy could aggravate fibrotic lesions in RIPF, downregulate the content of membrane Spry2, and upregulate the levels of p-c-Raf and p-ERK in lung tissue. It was found that knockdown of Spry2 in fibroblast abolished the upregulation of p-c-Raf and p-ERK by PTX. Both co-IP results and immunofluorescence staining showed that PTX increased the binding of Spry2 to tubulin, and microtubule depolymerizing agents could abolish PTX's inhibition of Spry2 membrane distribution and inhibit PTX's upregulation of Raf/ERK signaling. Both nintedanib and ERK inhibitor were effective in relieving PTX-exacerbated RIPF. Taken together, the mechanism of PTX's aggravating RIPF was related to its ability to enhance Spry2's binding to tubulin, thus attenuating Spry2's negative regulation on Raf/ERK pathway. SIGNIFICANCE STATEMENT: This study revealed that paclitaxel (PTX) concurrent radiation therapy exacerbates radiation-induced pulmonary fibrosis during the treatment of thoracic tumors, which is associated with PTX restraining Spry2 and upregulating the Raf/extracellular signal regulated kinase signaling pathway, and provided drug targets for mitigating this complication.

2024-04-01·American journal of respiratory cell and molecular biology

The Regulation of Fatty Acid Synthase by Exosomal miR-143-5p and miR-342-5p in Idiopathic Pulmonary Fibrosis

Article

作者: Rehbini, Ohoud ; Hayek, Hassan ; Bolla, Sudhir ; Bahmed, Karim ; Brandt, Thomas ; Criner, Gerard J ; Kishore, Raj ; Kosmider, Beata ; Bowler, Russell P ; Marchetti, Nathaniel ; Chatila, Wissam

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease caused by an aberrant repair of injured alveolar epithelial cells. The maintenance of the alveolar epithelium and its regeneration after the damage is fueled by alveolar type II (ATII) cells. Injured cells release exosomes containing microRNAs (miRNAs), which can alter the recipient cells' function. Lung tissue, ATII cells, fibroblasts, plasma, and exosomes were obtained from naive patients with IPF, patients with IPF taking pirfenidone or nintedanib, and control organ donors. miRNA expression was analyzed to study their impact on exosome-mediated effects in IPF. High miR-143-5p and miR-342-5p levels were detected in ATII cells, lung tissue, plasma, and exosomes in naive patients with IPF. Decreased FASN (fatty acid synthase) and ACSL-4 (acyl-CoA-synthetase long-chain family member 4) expression was found in ATII cells. miR-143-5p and miR-342-5p overexpression or ATII cell treatment with IPF-derived exosomes containing these miRNAs lowered FASN and ACSL-4 levels. Also, this contributed to ATII cell injury and senescence. However, exosomes isolated from patients with IPF taking nintedanib or pirfenidone increased FASN expression in ATII cells compared with naive patients with IPF. Furthermore, fibroblast treatment with exosomes obtained from naive patients with IPF increased SMAD3, CTGF, COL3A1, and TGFβ1 expression. Our results suggest that IPF-derived exosomes containing miR-143-5p and miR-342-5p inhibited the de novo fatty acid synthesis pathway in ATII cells. They also induced the profibrotic response in fibroblasts. Pirfenidone and nintedanib improved ATII cell function and inhibited fibrogenesis. This study highlights the importance of exosomes in IPF pathophysiology.

214

项与乙磺酸尼达尼布相关的新闻（医药）

2024-06-23

·药渡

欧洲杯来了！哪些国家最有望夺得“最佳药物管道”奖杯？

来源：药渡撰文：Maskey 编辑：哦呼欧洲杯激战正酣，各国球队为了荣誉和胜利而奋力拼搏。但如果换个角度，设想一下，若是让这些参加欧洲杯的国家在“最佳药物管道”这一特殊领域展开角逐，谁又将脱颖而出，问鼎桂冠呢？目前，世界各地的制药公司都在竞相开发最具创新性和最有效的常见人类疾病治疗方法。他们进行临床前研究和临床试验，希望他们的治疗方法能得到监管机构的批准。监管机构会为可能治疗严重疾病的新型试验药物授予突破性疗法认定和快速通道认定。近年来，越来越多的新型治疗方法（如细胞和基因疗法、单克隆抗体和抗体-药物偶联物）已获得监管机构的批准[1]。因此，制药公司正在加大对这些创新疗法的开发投入。一些最大的制药公司位于欧洲，所有这些公司都在建立庞大的创新疗法药物管线。图1.近年来美国食品药品监督管理局(FDA)批准的新分子实体（NME）和生物制剂的数量【1】图2.获得批准的单克隆抗体百分比【2】德国拜耳是德国领先的制药公司之一。老年性黄斑变性药物阿柏西普、前列腺癌药物达罗他胺、抗凝药物利伐沙班和慢性肾病药物Finerenone是其产品组合中最有价值的药物。该公司正在开发33种新疗法，其中19种疗法正在进行1期临床试验，3种疗法正在进行2期临床试验[3]。该公司正在测试几种创新的重组腺相关病毒 (rAAV) 基因疗法，用于治疗亨廷顿氏病、帕金森氏病和庞贝氏病。另一家德国制药公司勃林格殷格翰正在临床试验中测试40多种药物[4]。该公司已经开发出用于治疗多种疾病的小分子药物、T细胞接合剂和癌症疫苗。该公司的产品组合中包括有效的治疗药物，包括肺纤维化药物尼达尼布和抗糖尿病药物恩格列净。默克集团是另一家德国制药公司，正在开发10多种用于治疗癌症、自身免疫性疾病和疟疾的药物[5]。其药物管线中一些有前景的在研药物包括小分子药物Enpatoran、抗体药物偶联物M9140和免疫检查点抑制剂avelumab。 BioNtech也是一家德国大型生物制药公司，与辉瑞公司成功开发了COVID-19疫苗BNT162b2(Comirnaty)。该公司还在对患有不同类型癌症（如结直肠癌和胰腺导管腺癌）的患者测试癌症疫苗Autogene Cevumeran[6]。BioNTech SE正在临床试验中测试30多种治疗方法，包括mRNA治疗、细胞疗法、基于蛋白质的疗法和小分子免疫调节剂。这些治疗方法旨在治疗癌症和传染病。其管道中最有前途的候选药物之一是单克隆抗体Gotistobart，正在非小细胞肺癌患者中进行测试。该公司开发的其他重要药物包括双特异性抗体Acasunlimab、BNT312/GEN1042和BNT327/PM8002。德国规模较小的生物制药公司也在努力扩大其药物研发线。Ethris开发了一种新型吸入式mRNA治疗药物ETH47，用于治疗呼吸道病毒感染。海德堡制药公司研发线中的一种主要候选药物是用于治疗多发性骨髓瘤的抗体-药物偶联物HDP-101。Affimed开发了用于治疗非小细胞肺癌的双特异性先天细胞接合剂AFM24。Atai Life Sciences研发线中有几种用于治疗抑郁症和焦虑症的药物。法国法国最大的制药公司赛诺菲拥有庞大的药物管线，包括60多种临床阶段治疗药物[7]。该公司正在开发双特异性抗体、疫苗、单克隆抗体、NK细胞接合剂、酶替代疗法和基因疗法。其最畅销的药物是与Regeneron合作开发的单克隆抗体度匹鲁单抗。该药物已被批准用于多种适应症，例如特应性皮炎、嗜酸性食管炎和哮喘。其投资组合中的另一项重要资产是与阿斯利康合作开发的呼吸道合胞病毒 (RSV) 疫苗nirsevimab。其管线中的几种药物，如小分子药物SAR441566、单克隆抗体Amlitelimab和单克隆抗体Frexalimab，都有可能获得监管部门的批准并成为变革性的治疗方法。法国还有几家不太知名的制药公司，包括Genfit、Abivax和Enterome，它们正在研发新的创新疗法。Genfit正在开发治疗胆管癌和高氨血症的新疗法。今年6月，FDA加速批准其药物Elafibranor，用于治疗原发性胆汁性胆管炎。Amolyt Pharma的药物管线包括治疗肢端肥大症和甲状旁腺功能减退症的药物。Enterome正在开发新的基于肽的免疫疗法，用于治疗惰性非霍奇金淋巴瘤和胶质母细胞瘤。Abivax已开发小分子药物obefazimod，用于治疗溃疡性结肠炎和克罗恩病。Antabio正在开发治疗铜绿假单胞菌感染和医院内感染的药物。Ipen的临床阶段管线中有10多种药物，包括治疗偏头痛、阿拉吉耶综合征、多发性骨髓瘤和胆道闭锁的药物[8]。英国英国-瑞典制药公司阿斯利康拥有最大的药物管线之一，拥有超过90种不同的临床阶段治疗药物[9]。该公司正在开发用于治疗癌症、呼吸系统疾病、代谢疾病、肾脏疾病和心血管疾病的新药。它拥有非常强大的肿瘤学产品组合，包括抗体药物偶联物trastuzumab deruxtecan和酪氨酸激酶抑制剂奥希替尼。该公司还通过购买和公司收购在其管线中增加了嵌合抗原受体T细胞(CAR-T)疗法、呼吸道合胞病毒疫苗和2型糖尿病药物。其与第一三共联合开发的抗体药物偶联物Datopotamab deruxtecan可能很快会在美国获得监管部门的批准。葛兰素史克 (GSK) 已开发出60多种用于治疗艾滋病毒、癌症、传染病以及呼吸道和免疫疾病的药物。该公司最近开发的最成功的治疗方法之一是呼吸道合胞病毒疫苗Arexvy，该疫苗已获得FDA批准用于50岁以上的人群[10]。该公司在开发高效疫苗方面有着良好的记录，例如Gardasil、Arexvy和 Shingrix。今年，GSK收购了一家新兴生物制药公司Aiolos Bio，该公司开发了一种新型哮喘药物。 Verona Pharma开发了一种用于治疗慢性阻塞性肺病的药物Ensifentrine，今年可能会获得FDA的批准。Ellipses Pharma正在对2期临床试验中的四种药物进行评估[11]。该公司正在研发不同类别的药物，例如用于治疗癌症的双重抑制剂、纳米颗粒-药物偶联物和选择性雄激素受体调节剂 (SARM)。Evox Therapeutics正在临床前研究中开发外泌体递送的腺相关病毒(AAV) 基因疗法，用于治疗苯丙酮尿症和心血管疾病[12]。瑞士罗氏的研发管线中有70多种药物[13]。该公司开发的转化疗法之一是双特异性单克隆抗体Faricimab，用于治疗糖尿病性黄斑水肿和新生血管性年龄相关性黄斑变性。其他成功获得监管部门批准的重要治疗方法是抗体-药物偶联物polatuzumab vedotin-piiq双特异性单克隆抗体Emicizumab和双特异性抗体glofitamab-gxbm。其阿尔茨海默氏症药物gantenerumab在3期临床试验中未能显示出疗效。该公司已将小分子抑制剂camonsertib和双特异性抗体RG6286等抗癌药物从其管线中移除。罗氏正在优先考虑那些更有可能获得监管机构批准的治疗方法。诺华是全球销售额最大的制药公司之一。其药物研发管线中有超过60种治疗方法[14]。其研发管线包括单克隆抗体、CAR-T疗法、基因疗法、小分子抑制剂、合成小干扰RNA (siRNA) 和其他治疗不同疾病的药物。其产品组合中的重要资产是心力衰竭组合药物Sacubitril/valsartan、多发性硬化症药物 Ofatumumab、乳腺癌药物ribociclib和高脂血症药物inclisiran。其布鲁顿氏酪氨酸激酶(BTK)抑制剂remibrutinib很有可能被批准用于治疗慢性自发性荨麻疹。 ADC Therapeutics正在临床试验中测试大约3种治疗方法[14]。该公司开发了抗体药物偶联物loncastuximab tesirine-lpyl，该药物已获得FDA加速批准，用于治疗大B细胞淋巴瘤。Alentis Therapeutics的研发管线中有大约4种治疗方法，包括抗体药物偶联物和单克隆抗体[15]。图3.销售额最高的制药公司和治疗方法【16】丹麦丹麦制药公司诺和诺德是欧洲最大的制药公司之一。诺和诺德的药物管线包括35多种药物，其中大多数药物正在对患有非酒精性脂肪性肝炎和糖尿病等慢性疾病的患者进行测试[17]。其最成功的药物是用于治疗肥胖症和糖尿病的索马鲁肽。诺和诺德开发了一种每周一次的糖尿病药物胰岛素Icodec，该药物已获准在欧洲使用。Genmab有10多种治疗方法正在临床试验中测试。它与辉瑞联合开发了抗体-药物偶联物tisotumab vedotin，该药物已获准用于治疗宫颈癌。其T细胞结合双特异性抗体epcoritamab也已获准用于治疗弥漫性大B细胞淋巴瘤。比利时比利时生物制药公司Union Chimique Belge (UCB)正在开发用于治疗系统性红斑狼疮和严重纤维肌痛综合征等神经和自身免疫性疾病的药物。其研发管线中有大约10种小分子药物和单克隆抗体[18]。其药物bimekizumab已在美国获批用于治疗斑块状银屑病。荷兰荷兰制药公司Argenx开发了抗体片段efgartigimod，该片段已获批用于治疗全身性重症肌无力。该公司正在对患有干燥综合征和特发性炎症性肌病的患者进行efgartigimod测试。该公司正在研发的另一种药物是单克隆抗体Empasiprubart，该药物已被开发用于治疗多灶性运动神经病。总之，欧洲几家大型制药公司正在开发用于多种疾病的一流和一流药物。这些公司通过研究、收购和与其他公司的联合合作建立了强大的药物管线。在这些欧洲国家中，德国、英国、瑞士和法国都有成熟和新兴的生物制药公司，专注于开发创新疗法。大多数公司都开发出了有效的治疗方法，并已在许多国家获准使用。编者按：在这场假想的“最佳药物管道”欧洲杯中，每个国家都有机会展现自己的实力和风采，我们都期待看到其在“赛场”上展现出最佳的状态。未来我们应给予各国更多在医药研究上付出与收获的关注，以及他们为全人类的健康福祉所作出的杰出贡献。参考文献（可上下滑动）： [1] Senior, M. (2023). Fresh from the biotech pipeline: fewer approvals, but biologics gain share. nature biotechnology, 41(2), 174. [2] Walsh, G., & Walsh, E. (2022). Biopharmaceutical benchmarks 2022. Nature Biotechnology, 40(12), 1722-1760. [3] Bayer (2024, 30 April ). Pharmaceuticals Pipeline Overview and Progress. https://www.bayer.com/sites/default/files/ph-rd-pipeline-2024-05-final-1.pdf [4] Boehringer Ingelheim (n.d.). Boehringer Ingelheim Human Pharma Clinical Pipeline. https://www.boehringer-ingelheim.com/bipdf/pipeline-february-2024 [5] Merck Group (n.d.). HEALTHCARE PIPELINE. https://www.merckgroup.com/en/research/healthcare-pipeline.html [6] BioNTech SE (2024, 7 April). Three-year Phase 1 Follow-Up Data for mRNA-based Individualized Immunotherapy Candidate Show Persistence of Immune Response and Delayed Tumor Recurrence in Some Patients with Resected Pancreatic Cancer. https://investors.biontech.de/news-releases/news-release-details/three-year-phase-1-follow-data-mrna-based-individualized [7] Sanofi (n.d.). Our Pipeline. https://www.sanofi.com/en/our-science/our-pipeline [8] Ipsen (n.d.). Pipeline. https://www.ipsen.com/pipeline/ [9] AstraZeneca (n.d.). Our pipeline. https://www.astrazeneca.com/our-therapy-areas/pipeline.html#cvrm [10] GSK. (2024, 7 June). US FDA approves expanded age indication for GSK’s Arexvy, the first respiratory syncytial virus (RSV) vaccine for adults aged 50-59 at increased risk. https://www.gsk.com/en-gb/media/press-releases/us-fda-approves-expanded-age-indication-for-gsk-s-arexvy-the-first-rsv-vaccine-for-adults-aged-50-59-at-increased-risk/#:~:text=GSK%20plc%20(LSE%2FNYSE%3A,who%20are%20at%20increased%20risk. [11] Ellipses Pharma (n.d.). PORTFOLIO. https://ellipses.life/portfolio/ [12] Evox Therapeutics (n.d.). Pipeline. https://www.evoxtherapeutics.com/pipeline/ [13] Johnston, I (2024, 24 April). Roche cuts drug pipeline in effort to revitalise business. Financial Times https://www.ft.com/content/d2dfc0c4-85e0-4cf5-b926-c10d630b2772 [14] ADC Therapeutics (n.d.). Our Pipeline. https://www.adctherapeutics.com/our-pipeline/ [15] Alentis Therapeutics (n.d.). Novel therapies for cancer and fibrosis. https://alentis.ch/pipeline/ [16] Verdin, P. (2024). Top companies and drugs by sales in 2023. Nature reviews. Drug Discovery. [17] Novo Nordisk (n.d.). R&D pipeline. https://www.novonordisk.com/science-and-technology/r-d-pipeline.html [18] UCB (n.d.). PIPELINE. https://www.ucb.com/our-science/pipeline *声明：本文仅是介绍医药疾病领域研究进展或简述研究概况或分享医药相关讯息，并非也不会进行治疗或诊断方案推荐，也不对相关投资构成任何建议。内容如有疏漏，欢迎沟通指出！点击下方“药渡“，关注更多精彩内容美国Arthrosi公司创新药AR882溶解痛风石，2期临床试验成果亮相2024欧洲风湿病学大会全球First-in-class！迪哲医药戈利昔替尼重磅获批 2024年上半年FDA批准药物或新适应症（下）点击蓝字关注我们

基因疗法疫苗突破性疗法信使RNA临床1期

2024-06-10

·FiercePharma

With 2 planned launches, Boehringer Ingelheim looks to make a name for itself in oncology

Oncology is “not the largest” therapeutic area for Boehringer Ingelheim, but it's one where the company is “committed” to making a difference, global head of therapeutic areas Ioannis Sapountzis, Ph.D., said in an interview. (Boehringer Ingelheim) With 25 launches planned through 2030, Boehringer Ingelheim is gearing up for a busy few years. As a part of that, the German drugmaker is looking forward to flexing its oncology muscles with two new cancer drug launches in 2025. While the company’s overall pipeline is filled with early-stage assets acquired through recent business development deals, its oncology R&D efforts are largely centered around the late-stage prospects brigimadlin and zongertinib. Brigimadlin, a member of the MDM2-p53 antagonist drug class, recently entered a pivotal trial testing the candidate in patients with the rare cancer dedifferentiated liposarcoma (DDLPS). DDLPS is an ultra-rare aggressive cancer with “very, very dismal prognosis and a high unmet medical need,” Boehringer’s global head of therapeutic areas, Ioannis Sapountzis, Ph.D., said in an interview at this year’s annual American Society of Clinical Oncology (ASCO) conference in Chicago. The exec pegged the DDLPS patient population at around 3,000 worldwide. The disease space hasn’t seen “any innovation” in 40 years, Sapountzis said. Currently, DDLPS is treated primarily with chemotherapies including doxorubicin, which is nicknamed “red devil chemo” because of its harsh side effects. Brigimadlin is the product of 10 years of research and works by blocking the MDM2 oncoprotein from interacting with the cancer-surpressing p53 gene, helping patients fend off cancer cell growth, according to the company. Outside of DDLPS, the company aims to expand the drug's use to other sarcoma subtypes. At the ASCO conference, BI presented results from an early study testing the drug in combination with radiotherapy in newly diagnosed glioblastoma patients. The data support “continued investigation” of brigimadlin in the disease, investigators noted. As for zongertinib, the drug is a tyrosine kinase inhibitor being evaluated as a potential treatment for HER2-mutated non-small cell lung cancer (NSCLC). The company is looking to bring that therapy to market in the first half of 2025. Armed with an existing infrastructure for its marketed EGFR-mutated NSCLC med Giotrif, Boehringer is already busy building out its commercial resources, Sapountiz said. Besides Giotrif, BI's other commercial cancer drug is Vargatef for certain lung cancer patients. Oncology is “not the largest” therapeutic area in the Boehringer’s portfolio, Sapountzis acknowledged, but it’s one where the company has “been committed to really making a difference." Dealmaking focus BI has long been active in the M&A space and is “always looking for innovation,” Sapountzis noted. Just last month, the drugmaker shelled out 38.8 million euros ($42 million) to longtime partner OSE Immunotherapeutics in exchange for a preclinical anti-PD1/cytokine med and an expansion of a prior oncology research effort. So far this year, Boehringer has also signed a T-cell anti-cancer therapy partnership with 3T Biosciences and a collab with Suzhou Ribo Life Science and Ribocure Pharmaceuticals to use RNA to treat metabolic-associated steatohepatitis. “We want to be truly collaborative in everything we do,” Sapountzis said. “We feel that together, we can achieve more; together, we can really advance treatments much better.”

ASCO会议

2024-06-07

·Pharmaceutical Technology

Agomab wins FDA orphan drug status for idiopathic pulmonary fibrosis asset

Agomab is now eligible for market exclusivity and a range of financial incentives. Image credit: Shutterstock / HammadKhn. Six months after kicking off a Phase I trial for idiopathic pulmonary fibrosis (IPF) treatment AGMB-447, Agomab Therapeutics has now secured a US Food and Drug Administration (FDA) orphan drug designation for the asset. Recommended Buyer's Guides Buyer's Guide Leading Guide to Packaging Materials, Containers and Containment Services for the Pharmaceutical Industry Buyer's Guide Leading Guide to Compliance Software for the Pharmaceutical Industry The Belgium-based biotech will now be in line for tax credits for US-based clinical trials and, if the therapy is approved, the potential for seven years of market exclusivity in the designated indication. IPF is a rare, chronic lung disease that affects the air sacs – called alveoli – in the lungs. The condition is characterised by thickening of lung tissue that becomes stiff, causing breathing difficulties. It is not known what causes the disease, though the risk is increased with smoking and a family history of IPF. There are currently two FDA-approved drugs for IPF, Boehringer Ingelheim’s Ofev (nintedanib) and Genentech’s Esbriet (pirfenidone). Ofev is a tyrosine kinase inhibitor whilst Esbriet targets TGF-beta, a chemical mediator that plays a role in development of fibrosis. Agomab has gone down a similar route to Genentech, with AGMB-447 blocking the action of the TGFβ type 1 receptor. Agomab’s USP is that AGMB-447, which is inhaled, inhibits the TGFβ type 1 receptor, also known as ALK5, only in the lung. The biotech has achieved this by designing the drug to be rapidly metabolised through hydrolysis in the plasma, preventing exposure throughout the whole body. See Also: The tiny pills that may send shockwaves across immunology Roche’s PI3K inhibitor secures breakthrough status in breast cancer Agomab is evaluating AGMB-447 in a placebo-controlled Phase I trial that aims to enrol 76 patients with IPF. Participants will either receive a single dose or multiple doses of AGMB-447, the latter treatment will occur in two cohorts over seven days or 14 days. The randomised trial has primary endpoints comprising safety assessments up to eight weeks after therapy. Secondary endpoints include pharmacokinetic measurements. The biotech dosed the first patient in December 2023. Agomab’s chief medical officer Philippe Wiesel said: “As we progress through our ongoing first-in-human Phase I trial, we look forward to evaluating the data from the single ascending dose and multiple ascending dose evaluation of AGMB-447 in healthy subjects and IPF patients.” Agomab secured $100m in Series C financing in October 2023. In a statement at the time, the biotech said it would use part of the funds to progress Crohn’s disease candidate AGMB-129 – also an ALK5 inhibitor – through Phase II trials. Agomab’s designation comes only a few weeks after Alentis Therapeutics won orphan drug status for its candidate lixudebart in IPF. In the same announcement as its orphan drug designation, Alentis reported positive safety results from a Phase I trial evaluating lixudebart in IPF patients.

临床1期孤儿药临床结果临床2期上市批准

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KEGG	Wiki	ATC	Drug Bank
D10396	乙磺酸尼达尼布	L01XE31	DB09079

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适应症	国家/地区	公司	日期
进行性肺纤维化	美国	Boehringer Ingelheim Pharmaceuticals, Inc.	2020-03-09
间质性肺疾病	日本	Nippon Boehringer Ingelheim Co., Ltd.	2019-12-20
系统性硬皮病	日本	Nippon Boehringer Ingelheim Co., Ltd.	2019-12-20
系统性硬化相关的间质性肺病	美国	Boehringer Ingelheim Pharmaceuticals, Inc.	2019-09-06
肺腺癌	欧盟	Boehringer Ingelheim International GmbH	2014-11-21
肺腺癌	冰岛	Boehringer Ingelheim International GmbH	2014-11-21
肺腺癌	列支敦士登	Boehringer Ingelheim International GmbH	2014-11-21
肺腺癌	挪威	Boehringer Ingelheim International GmbH	2014-11-21
非小细胞肺癌	欧盟	Boehringer Ingelheim International GmbH	2014-11-21
非小细胞肺癌	冰岛	Boehringer Ingelheim International GmbH	2014-11-21
非小细胞肺癌	列支敦士登	Boehringer Ingelheim International GmbH	2014-11-21
非小细胞肺癌	挪威	Boehringer Ingelheim International GmbH	2014-11-21
特发性肺纤维化	美国	Boehringer Ingelheim Pharmaceuticals, Inc.	2014-10-15

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适应症	最高研发状态	国家/地区	公司	日期
慢性间质性肺病	申请上市	欧盟	Accord Healthcare SLU	2024-02-22
翼状胬肉	临床3期	美国	Cloudbreak Therapeutics LLC初创企业	2022-06-30
翼状胬肉	临床3期	中国	Cloudbreak Therapeutics LLC初创企业	2022-06-30
翼状胬肉	临床3期	澳大利亚	Cloudbreak Therapeutics LLC初创企业	2022-06-30
翼状胬肉	临床3期	印度	Cloudbreak Therapeutics LLC初创企业	2022-06-30
翼状胬肉	临床3期	新西兰	Cloudbreak Therapeutics LLC初创企业	2022-06-30
肺纤维化	临床3期	美国	Boehringer Ingelheim International GmbH	2015-11-30
肺纤维化	临床3期	日本	Boehringer Ingelheim International GmbH	2015-11-30
肺纤维化	临床3期	阿根廷	Boehringer Ingelheim International GmbH	2015-11-30
肺纤维化	临床3期	澳大利亚	Boehringer Ingelheim International GmbH	2015-11-30

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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


NCT02902484 (ESMO_GI2024) 人工标引	临床1期	晚期胰腺腺癌	13	Nintedanib combination with chemotherapy gemcitabine (Gem) and nab-paclitaxel (Nab-P)	膚醖製鹹顧繭願齋艱糧(鹹醖觸鏇構鹽顧壓鹹淵) = nintedanib was 200 mg twice daily 膚壓顧積憲淵築糧鑰觸 (襯鹹蓋鹽製範窪膚鬱獵 ) 更多	积极	2024-06-27
NCT02902484 (CTgov)	临床1/2期	晚期胰腺腺癌	14	Nab-paclitaxel+gemcitabine+nintedanib (All Participants)	網襯壓範鏇願選鑰淵廠(廠廠壓鏇繭築艱觸鬱夢) = 憲構願鹹憲積膚壓壓膚範獵夢齋製壓遞網餘獵 (遞憲網廠觸衊壓繭鹹鏇, 窪夢繭鹽蓋淵醖廠鹽鬱 ~ 製繭網糧願繭夢鏇襯蓋)	-	2024-06-03
				Nintedanib (Nintedanib 150 mg)	簾壓膚鹽構艱網鏇壓壓(構積壓繭醖糧範餘觸網) = 鑰膚築願衊憲範憲鬱範艱簾鬱繭鏇繭鏇範選襯 (壓齋顧網醖壓顧製衊觸, 壓憲齋簾淵壓範範襯鏇 ~ 襯觸積憲範糧醖蓋襯衊) 更多
NCT05262751 (CTgov)	临床1期	-	21	Ofev (Cohort 1: Reference (R))	鏇餘積製選遞願艱憲遞(鹽願築蓋衊艱觸範選鏇) = 鏇壓壓觸鏇願觸觸餘顧鹽獵鑰夢鹽簾遞糧夢觸 (蓋壓淵廠積獵築選範鏇, 構淵齋願艱壓簾積遞範 ~ 衊願積繭願窪鏇製築膚) 更多	-	2024-05-29
				Nintedanib (Cohort 1: Test Treatment 1 (MR1-1))	鏇餘積製選遞願艱憲遞(鹽願築蓋衊艱觸範選鏇) = 顧鏇壓顧膚夢醖觸鏇鏇鹽獵鑰夢鹽簾遞糧夢觸 (蓋壓淵廠積獵築選範鏇, 衊鹽膚顧艱淵簾範憲鹽 ~ 顧顧夢憲網衊簾醖構獵) 更多
NCT03313180 (CTgov)	临床3期	系统性硬化相关的间质性肺病	444	Nintedanib	壓觸窪顧衊衊顧構淵製(觸簾鬱簾鏇壓壓繭衊襯) = 繭鏇網夢蓋醖簾觸餘顧製憲鬱壓餘壓簾鹽鏇廠 (遞鑰窪獵獵構積繭蓋製, 積繭艱醖製鏇積醖廠顧 ~ 積遞淵簾壓糧醖鏇壓鏇) 更多	-	2024-02-20
ACR2023	N/A	进行性肺纤维化 serum KL-6	25	Nintedanib + Immunosuppressive Agents	積願築壓壓製繭艱醖獵(簾網醖窪餘網窪製壓獵) = 13 patients 壓築積積顧淵餘齋選鏇 (夢壓繭齋積網鬱繭壓廠 ) 更多	积极	2023-11-12
				Nintedanib
NCT03820726 (CTgov)	临床3期	进行性肺纤维化	435	nintedanib	遞艱醖網鹹糧膚獵網築(齋廠衊蓋淵觸襯鏇鬱網) = 願觸衊築觸憲鏇廠繭觸願構構窪壓網淵範繭壓 (廠繭積膚築齋衊廠獵淵, 壓齋鹹糧淵構鏇繭淵製 ~ 繭齋築構鹽範鹽選遞膚) 更多	-	2023-09-13
JPRN-jRCTs031190119 (TORG 1835 / NEXT-SHIP, WCLC2023) 人工标引	临床2期	小细胞肺癌	33	Carboplatin+Etoposide+Nintedanib	膚製糧獵衊鏇糧艱艱壓(顧鏇獵積夢壓鬱醖觸衊) = 襯膚鑰簾願襯顧憲夢壓築齋觸製築窪醖壓構醖 (製鹹鏇築衊壓構願築淵, 0.2 ~ 13.6) 达到更多	积极	2023-09-12
NCT04938453 (CTgov)	临床1期	-	20	Nintedanib (Nintedanib 1 X 100 mg (R))	鏇簾鹹積鏇鬱構壓襯鹽(範壓遞鏇艱製齋製鏇範) = 醖顧憲願網構艱簾襯鑰襯窪醖壓襯餘繭齋襯糧 (窪夢積鏇繭獵遞構顧願, 壓繭鏇鏇襯鹽鏇範簾窪 ~ 顧構鹽鬱憲壓餘糧憲獵) 更多	-	2023-07-17
				Nintedanib (Nintedanib 4 X 25 mg (T))	鏇簾鹹積鏇鬱構壓襯鹽(範壓遞鏇艱製齋製鏇範) = 選鹽繭遞積網窪遞蓋築襯窪醖壓襯餘繭齋襯糧 (窪夢積鏇繭獵遞構顧願, 獵觸積顧艱廠鹹積選鹹 ~ 顧鏇築憲積網膚餘淵遞) 更多
INBUILD (EULAR2023)	N/A	进行性肺纤维化 KL-6	24	Nintedanib + Immunosuppressive agents	夢襯齋網鹹鬱醖蓋壓鑰(鑰鏇觸構構網遞簾製鏇) = 鹽艱糧糧餘餘製願齋襯窪糧顧膚憲襯鹹鏇網齋 (齋鹽選廠壓憲鏇廠壓範 ) 更多	积极	2023-05-31
				Nintedanib	夢襯齋網鹹鬱醖蓋壓鑰(鑰鏇觸構構網遞簾製鏇) = 鹹夢憲願製選構淵製壓窪糧顧膚憲襯鹹鏇網齋 (齋鹽選廠壓憲鏇廠壓範, mL) 更多
EULAR2023	N/A	结缔组织病相关间质性肺疾病	22	Nintedanib	壓網衊構廠願膚鬱淵製(獵膚鏇觸廠鬱膚襯糧鹹) = The most common side effect of nintedanib was diarrhea 繭壓衊繭鹹鑰積鏇膚夢 (簾鬱製繭鬱齋醖鹹衊艱 )	-	2023-05-31