Netupitant

HONG KONG, Nov. 7, 2024 /PRNewswire/ -- On November 5, the 7th China International Import Expo (CIIE) opened at the National Exhibition and Convention Center in Shanghai. As a seven-time attendee of the CIIE, Fosun showcased the latest achievements in innovation and global operations at its Fosun Pharma booth in Hall 7.1, featuring cutting-edge medical devices and innovative pharmaceuticals that made their debut in China. Guo Guangchang, Chairman of Fosun International, remarked, "Over the past seven years, CIIE has improved every year, becoming a window for China to build a new development framework, a platform for high-level openness, and an international public product for global sharing. Fosun has been a participant, witness, and beneficiary of the CIIE. Leveraging the CIIE platform, our long-term innovations have continually been put into practice, transforming many 'exhibits' into 'products', and converting many overseas partners from 'exhibitors' into 'investors'. This year, we continue to showcase our latest achievements in integrated innovation in the medical device and health sector, including several 'world's firsts' and 'China's firsts'. We firmly believe that China remains a significant opportunity for global development. Together with more overseas companies and global partners, we will promote more cutting-edge innovations to take root in China, moving forward and achieving mutual success on the grand stage of the CIIE." Stars of CIIE Taking Root, Transforming Ion from "Exhibit" to "Product" Healthcare is one of Fosun's main businesses. With CIIE's "spillover effect," several star products from Fosun, supported by the CIIE "accelerator" effect, have successfully entered the market to serve Chinese patients, transforming from "exhibits" into "products". This year, following the popular da Vinci Surgical System, the Ion Robotic Bronchoscopy made its CIIE debut after receiving domestic approval. Since its first appearance at the CIIE in 2019, Ion caught the attention of visitors. By the end of 2022, Ion entered the National Medical Products Administration's 'Green Channel' for innovative products and gained approval in March 2024, with the first commercial application completed in September. Lung cancer is considered the leading cause of cancer deaths, with 1.06 million new cases in China in 2022. The five-year survival rate is only 19.7%, and bronchoscopy is a key diagnostic tool for early lung cancer detection. The Ion bronchoscopy navigation control system offers innovative features for precise, convenient clinical diagnosis, providing new options for patients. By the third quarter of this year, 736 Ion systems had been installed globally, with over 150,000 Ion procedures performed. Outside the CIIE exhibition hall, Fosun is accelerating the localization of advanced medical devices. In June this year, Intuitive Fosun's headquarter industrial base was launched in Shanghai, marking Intuitive's largest R&D, production, and training center in the Asia-Pacific region. At this base, in addition to the Ion shape-sensing bronchoscopy control system, advanced products and core components, including the da Vinci surgical robot, are gradually achieving "Made in China, joint R&D, and global sales." Accelerating Integrated Innovation to Lead in Neurological Disease Treatment Transformation Fosun has long committed to investing in cutting-edge areas of healthcare, fostering a continuous stream of breakthrough "solid achievements" through an open innovation ecosystem involving independent R&D, collaborative development, licensing, and industry investment. These innovations are continually transformed into new drivers of growth. At this year's CIIE, Fosun introduced several latest products that are leading industry transformation. In the field of neurological disease treatment, especially for conditions like essential tremor and Parkinson's disease, patients have long faced challenges with unmet clinical needs. Traditional drug and surgical treatments often have limitations, but advancements in non-invasive treatment technologies have brought new hope to these patients. Fosun has actively responded to this unmet clinical need. At this year's CIIE, the new V2 model of the CNS (Central Nervous System) innovative treatment technology, the V2 model of "Exablate Neuro FUS system" made its debut in China, generating high expectations within the industry. This new model has already received CE certification in Europe and FDA approval in the United States and submitted a registration application to China's National Medical Products Administration in 2024. The V2 model's innovation lies in providing a non-invasive surgical solution for clinically drug-resistant essential tremor and tremor-dominant Parkinson's disease, while also being compatible with a broader range of MRI models, further enhancing the accessibility of this technology. Last year, Fosun, in partnership with Insightec, showcased the "Exablate Neuro" at CIIE, drawing much attention and continuous interest in collaboration. Leveraging the CIIE's "spillover effect", Fosun Pharma and Insightec established a joint venture, Fosun-Insightec, in February this year. The venture is focused on the marketing and developing clinical efforts of Exablate Neuro FUS system in improving the lives of patient living with essential tremor and Parkinson's disease, working to help them regain their quality life and wellbeing. Focusing on innovating to meet real customer needs is a core methodology for Fosun. Data shows that Fosun has made long-term investments in technological innovation, with an investment of RMB 3.5 billion in the first half of this year. Connecting Globally to Enhance Accessibility of Innovative Drugs, Benefiting more Patients Leveraging the CIIE's openness, Fosun also presented innovative products focused on solid tumors, hematological tumors, and immune-inflammatory conditions. Fosun's seven-year journey at CIIE has facilitated the introductions of global products and enabled the export of local innovations to benefit more patients worldwide. In 2017, Fosun introduced China's first CAR-T cell therapy product, Yi Kai Da (ejilunsai injection). Since then, by continuously participating in the CIIE, Fosun has enabled the public to gain an in-depth understanding of this advanced therapy. At this year's CIIE, Fosun highlighted Yi Kai Da's latest developments in the "accessibility and treatability" in lymphoma treatment. Yi Kai Da is now included in over 110 urban customized commercial health insurances and more than 80 commercial insurances, created a new path of payment mode for patients; and over 170 high-standard treatment centers across 28 regions in China providing treatments for over 900 lymphoma patients, achieving revolutionary innovative breakthroughs for cancer care. As a global company rooted in China, Fosun has an extensive industrial presence in over 35 countries and regions worldwide, with robust global R&D capabilities and impressive progress. This year, Fosun also showcased several innovative products, including the world's first and only dual-channel fixed-dose combination oral formulation, Akynzeo® oral (Netupitant and Palonosetron hydrochloride), which blocks both NK-1 and 5-HT3 receptors; the immunoglobulin Thymoglobulin® for improving transplant patient outcomes; the world's first oral targeted medication for psoriasis, Otezla® (apremilast tablets); a new third-generation COMT inhibitor Ongentys® (Opicapone) for managing symptom fluctuations in adult Parkinson's disease patients; and Parsabiv® (Etelcalcetide Hydrochloride Injection), the only peptide-based calcimimetic for treating secondary hyperparathyroidism in adult dialysis patients with chronic kidney disease. Guo Guangchang concluded, "Participating in CIIE has been a top priority for Fosun for seven consecutive years. We have witnessed CIIE become a crucial platform for global companies to share in China's development opportunities and deepened our global partnerships through this platform. We believe the CIIE stage will continue to expand, and Fosun's journey of innovation and globalization will grow broader." SOURCE Fosun WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

关于NK1R神经激肽受体 1 (Neurokinin 1 receptor, NK1R), 又被称为速激肽受体 1 (tachykinin receptor 1, TACR1) 或物质P受体 (substance P receptor, SPR), 隶属于 GPCR 家族，主要存在于中枢神经系统和周围神经系统中，其内源性配体是 P 物质，它对其他一些速激肽也有一定的亲和力。物质 P (一种神经肽) 通过激活 NK1R，对突触神经传递进行持久调节。例如，物质 P 在神经系统中的作用对疼痛、情绪、呼吸和恶心有重要影响，其次，物质 P 在其他组织中的作用与炎症或平滑肌收缩有关。大量研究表明，NK1R 拮抗剂对物质 P 活性的抑制可能会导致对疼痛、炎症和情绪失调的有效治疗。根据智慧芽新药情报库统计，到目前为止，靶向 NK1R 的拮抗剂开发主要用于临床治疗化疗引起的恶心和呕吐。全球获批的 NK1R 拮抗剂一共5款，包括 Fosnetupitant, Rolapitant，Netupitant (与5-HT3R 拮抗剂 Palonosetron 的复方制剂)，Fosaprepitant，Aprepitant 等；在中国获批上市的主要是后三者。5款靶向 NK1R 的拮抗剂药物Aprepitant 是全球首款获批上市的 NK1R 受体拮抗剂产品，由 Merck 公司原研并进行临床适应症开发。Aprepitant 可与其他止吐药联合使用，用于预防与高致吐性癌症化疗初始疗程和重复疗程相关的急性和迟发性恶心和呕吐。Aprepitant (L-754030, MK-869) 是一种选择性高亲和力人源 NK1R 受体拮抗剂，它对5-羟色胺（5-HT3）、多巴胺和皮质类固醇受体几乎没有亲和力，而这些受体也是现有化疗引起的恶心和呕吐疗法的靶点。1999 年，《新英格兰医学杂志》首次发表了一项使用选择性神经激肽-1 受体拮抗剂 (Aprepitant, L-754030) 对接受抗癌化疗的患者的止吐效果。结果显示，在化疗病人的急性呕吐期，每日服用 L-754,030 (第 1 组) 和单次服用 (第 2 组) 中 93% 的患者没有呕吐，而对照组 (第 3 组) 中 67% 的患者没有呕吐。在迟发性呕吐期，第 1 组有 82% 的患者没有呕吐，第 2 组有 78% 的患者没有呕吐，第 3 组有 33% 的患者没有呕吐。整体而言，每日服用 L-754,030 在迟发性呕吐阶段的恶心评分中位数明显低于对照组。L-754,030 治疗未引发严重不良事件。随后的临床研究，进一步表明，每日口服一次 NK1R 受体拮抗剂 MK-869 可有效减少大剂量化疗治疗后的延迟性呕吐和恶心。与此同时，MK-869 与 5HT3R 受体拮抗剂和 dexamethasone 的三联疗法对急性呕吐的控制效果最佳，这进一步扩展NK1R 与 3-HT3R 双靶点联用治疗的可能性。2003 年，多项相继公布的临床研究证据，验证了 Aprepitant 对于化疗引起的恶心和呕吐的安全性和疗效。Aprepitant 于 03 年 3 月被美国 FDA 批准上市。Fosaprepitant (L-758,298, MK-0517) 是由 Merck 公司开发上市的全球第二款 NK1R 受体拮抗剂，首批适应症依然为化疗引起的恶心和呕吐。L-758,298 是 L-754,030 的一种水溶性静脉注射原药，它是一种强效、选择性的NK1受体拮抗剂。根据 2001 年公布的一项双盲、随机、对照临床研究试验结果，评估了预防化疗治疗后急性（0-24 h）和延迟（第 2-7 天）呕吐的效果。在急性期，L-758,298 组和 5-HT3R 拮抗剂 ondansetron 组无呕吐的患者比例分别为 37% 和 52%（组间无显著差异）。在延迟期，L-758,298治疗组和 L-754,030 治疗组无呕吐的患者比例分别为72%和30%。与 ondansetron 组相比，L-758,298治疗组在延迟期的平均恶心评分分布较低。2007 年，Merck 团队进一步研究了 Fosaprepitant 在健康受试者中的耐受性以及与 Aprepitant 的生物等效性。72 小时的血浆浓度检测结果显示，静脉注射制剂 115 mg Fosaprepitant 与 125 mg Aprepitant 生物等效。2008 年后，Fosaprepitant 在多个国家和地区获批上市后。Netupitant/Palonosetron 是由瑞士Helsinn 医疗公司开发的一款 NK1R 受体拮抗剂Netupitant 与 5-HT3R 拮抗剂 Palonosetron 组成的复方制剂，首批适应症为化疗引起的恶心和呕吐。2019年后，多项 Netupitant/Palonosetron 复方制剂的临床研究成果先后发表。国内市场方面，2017年，Helsinn 医疗公司与诺思格（北京）医药科技提交上市申请。2019年8月，奈妥匹坦帕洛诺司琼胶囊 (奥康泽, Netupitant/Palonosetron) 在中国成功获批，用于成人患者预防高度致吐性化疗引起的急性恶心呕吐和延迟性恶心呕吐，预防中度致吐性化疗引起的急性恶心呕吐和延迟性恶心呕吐。2021 年 10 月，上海复星医药从 Helsinn 医疗公司共同宣布，双方签署独家许可和分销协议，Helsinn 授权复星医药在中国内地和港澳地区独家分销、推广和销售奥康泽。2023年01月，《国家基本医疗保险、工伤保险和生育保险药品目录（2022年）》正式公布，复星医药的止吐药物奈妥匹坦帕洛诺司琼胶囊成功进入国家医保目录。另外，多个药企也陆续启动奈妥匹坦帕洛诺司琼胶囊的仿制药研究，其中，四川科伦和齐鲁药业的等效性临床研究已完成。2023年4月，四川科伦药业递交的奈妥匹坦帕洛诺司琼胶囊仿制药上市申请获受理，国内首家报产的本土药企。Fosnetupitant 是 Helsinn 医疗公司开发的一款 NK1R 受体拮抗剂，是 Netupitant 的原药。2018 年，美国 FDA 批准 Fosnetupitant 与 Palonosetron 固定剂量复方制剂的静脉注射剂型合用，该复方制剂在欧盟和加拿大也被批准用于临床治疗呕吐用途。据研究，患者或健康受试者单次静脉注射 235 mg Fosnetupitant 和 0.25 mg Palonosetron 后，Fosnetupitant 的最大浓度在 30 分钟输注结束时达到。每种动物的口服生物利用度差异很大，大鼠、狗和猴子的生物利用度分别为42-105%、34-83%和37-62%。Rolapitant (SCH-619734) 是由先灵葆雅公司（Schering Plough Corporation）原研开发的一款高选择性 NK1R 受体拮抗剂。2009 年全球经济危机，默沙东以411亿美元收购先灵葆雅。收购时“被赠送”的 K 药，后来成为可默沙东王牌产品。也是 2009 年，OPKO Health 公司从先灵葆雅收购了 Rolapitant 和其他神经激肽-1 资产，并于 2010 年将 Rolapitant 的开发、生产和商业化独家授权给专注于肿瘤的生物制药公司 TESARO 公司。根据2009年发表的一篇研究论文，Rolapitant 是一种具有选择性、生物可利用性、中枢神经系统穿透性的神经激肽 NK1R 受体拮抗剂，可在呕吐动物模型中显示出行为效应。体外研究表明，Rolapitant 对人类 NK1R 受体的亲和力为 0.66 nM，对人类 NK2R 和 NK3R 亚型的选择性大于 1000 倍。（来源于，DOI: 10.1016/j.pbb.2012.03.021）在静脉注射和口服最低有效剂量为 0.1 mg/kg的情况下，Rolapitant 可逆转 NK1R 激动剂诱发的沙鼠足部叩击长达 24 小时。Rolapitant 在雪貂急性和延迟性呕吐模型中的活性剂量分别为 0.1 mg/kg 和 1 mg/kg，这与其他 NK1 拮抗剂的临床数据一致。止吐药的临床疗效与雪貂致呕吐模型的疗效高度相关，这表明 Rolapitant 是这一适应症的可行临床候选药物。2015 年，TESARO 公司团队在《柳叶刀-肿瘤学》杂志发表了两项临床3期研究成果，分别研究了 Rolapitant 预防癌症患者接受中度致吐化疗或蒽环类和环磷酰胺方案、接受顺铂为基础的高致吐性化疗后化疗引起的恶心和呕吐的安全性和有效性。同年7月，恒瑞医药发布公告称，公司与美国 Tesaro 公司达成协议，引进 Tesaro 公司用于肿瘤辅助治疗的止吐专利药 Rolapitant，恒瑞将被授权负责该药在中国的临床开发、注册和市场销售。目前该药处于申请上市阶段。以上文章来源于GPCR drug diacovery，作者段思研本文仅作信息交流之目的，文中观点不代表相关疾病治疗立场，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。