Desidustat

7月5日，石药集团中诺药业宣布，其开发的罗沙司他胶囊获NMPA批准上市。该品种是首款在国内获批上市的罗沙司他胶囊仿制药。 part 01 在中国首发上市的HIF-PH抑制剂 罗沙司他原研公司为珐博进（FibroGen），是一款小分子缺氧诱导因子-1脯氨酰羟化酶（HIF-PH）抑制剂。其作用机理为通过模拟低氧环境下的生理反应，激活HIF通路，促进内源性促红细胞生成素（EPO）的产生，改善铁的吸收和动员以及下调铁调素，促进红细胞生成，以纠正贫血。 常氧及低氧情况下HIF通路机制 来源：参考2 2004年9月，安斯泰来与珐博进达成协议，获得罗沙司他的日本权益。 2006年4月，安斯泰来扩大协议至欧洲、独联体国家（CIS）、中东和南非地区。 2013年7月，阿斯利康出资8.15亿美元获得罗沙司他在美国、中国以及安斯泰来未授权地区的开发和商业化权益（2024年2月已终止）。 2018年12月，罗沙司他首次在中国获批上市（商品名：Evrenzo），用于治疗正在接受透析治疗的患者因慢性肾脏病（CKD）引起的贫血。值得一提的是，这一获批让中国第一次成为首创新药的首批国家，标志着中国在全球医药创新领域的重要地位。 2019年，罗沙司他的适用人群扩大至非透析CKD患者。2023年8月，罗沙司他新适应症再次获CDE受理，用于治疗化疗引起的贫血（CIA）。根据珐博进2023年财报，去年罗沙司他在中国销售额为2.84亿美元，同比增长36%。 珐博进2023年财报 然而就是这么一款销售额增长强劲的产品，在美国的上市之路却充满坎坷，最终折戟。 part 02 罗沙司他梦碎美利坚，阿斯利康提分手 CKD正逐渐成为影响人类健康的重大挑战。根据国际肾脏病学会（ISN）的数据，全球CKD的患病率约为10%—15%的成年人口。随着全球人口老龄化，CKD的患病率预计将继续上升。 据统计，我国CKD患者约1.2亿，50%以上患者合并贫血，透析患者贫血患病率高达95%。过去，治疗肾性贫血的药物主要是促红细胞生成制剂（ESAs）和铁剂，但它们具有一定的局限性：大剂量ESA治疗可增加肿瘤、心血管事件和脑血管事件的风险；另外对于功能性铁缺乏的患者，其储存铁处于相对较高水平，过度铁剂治疗使患者更易发生感染、过敏和铁过载等风险，间接增加死亡风险。 相对与ESAs等传统治疗药物，罗沙司他的优点在于：在促进患者内源性EPO生成的同时，还可以改善患者自身对铁的吸收与利用，对静脉铁依赖性减弱，避免了静脉铁剂应用的不良反应；另外，罗沙司他口服给药、无需注射的特性，也避免了针剂使用的不便，提升患者的依从性。 尽管如此，罗沙司他仍未敲开FDA的大门。2019年5月，珐博进和阿斯利康联合公布了罗沙司他的安全性结果，但该结果被FDA认为其在心血管副作用上相较于传统的促红细胞生成素类药物阿法依泊汀，并未体现出优势，并对其上市评定日期一推再推。 2020年12月， FDA要求阿斯利康和珐博进澄清III期临床数据分析，并将罗沙司他审批上市的时间再次推迟3个月。有意思的是，在推迟期间，珐博进还公开承认更改了部分用于分析罗沙司他在CKD患者的心脏安全性数据，其股价还因此大跌43%。 紧接着，FDA对罗沙司他的内部审查也发现了更多的安全性问题，如死亡、血栓和感染风险增加等。最终在2021年8月，珐博进收到了FDA的最终判决：“目前暂时不会批准罗沙司他的上市申请，并要求珐博进在再次提交上市申请之前进行额外的临床研究。” 伴随着罗沙司他在美国上市被拒，阿斯利康提出了“分手”。2024年2月26日，珐博进宣布已与阿斯利康达成一致，将终止2013年7月30日签订的关于罗沙司他的合作协议。珐博进将重新获得罗沙司他在美国及其他地区的所有权利（除了中国和韩国）。 图片来源：珐博进官网 虽然罗沙司他在冲击美国市场的过程中吃到了闭门羹，但在其他国家的获批一路顺遂。目前，罗沙司他已在日本、智利和韩国等国获批上市，并且在中国递交的治疗化疗引起的贫血（CIA）新适应症申请已获CDE受理。 part 03 HIF-PH抑制剂研发现状 对于CKD患者来说，贫血是常见并发症之一。这是因为正常情况下，健康的肾脏会自然分泌EPO，促进红细胞生成。而CKD患者的肾功能会逐渐丧失，最终出现肾衰竭。肾功能受损后，肾脏生成EPO的水平将下降或丧失，从而导致贫血。HIF-PH抑制剂则通过增加内源性EPO的生成、改善铁的利用率和降低铁调素的水平来促进红细胞生成，是治疗CKD的有效策略。 目前在全球市场，共有六款HIF‐PH抑制剂获批上市，除了罗沙司他，还有Japan Tobacco/信立泰的恩那度司他（Enarodustat）、拜尔的莫立司他（Molidustat）在日本获批上市、GSK的达普司他（Daprodustat）在美国和日本两地上市、康哲药业的德度司他在印度获批上市。 由于珐博进在美国市场闯关失败，这给细分领域带来了一定的市场空白。2023年2月，GSK的达普司他片剂成为FDA首个批准的HIF-PH抑制剂。 在国内，处于临床开发阶段的有三生制药HIF-117、恒瑞医药DDO-3055、东阳光药业HEC-53856等。 据估计，中国有超过1.2亿CKD患者，CKD1～5期患者贫血患病率依次为：22.0%、37.0%、45.4%、85.1%和98.2%。而治疗达标率（血红蛋白水平达到靶目标值（110～120 g/L））对于非透析CKD贫血来说仅为8.2%，因此国内存在巨大的未被满足的治疗需求。这也解释了阿斯利康没有放弃中国市场的原因。 总的来说，HIF-PH抑制剂的出现，引领了肾性贫血治疗模式的变革。目前，该赛道尚不拥挤，但未来在仿制药和创新药的共同角逐下，竞争将逐渐激烈。国内在此布局的药企应抓住窗口期，早日将产品推向市场。 参考来源 1.公司官网 2.MLA style:Press release.NobelPrize.org.Nobel Prize Outreach AB 2024.Tue.16 Apr 2024. 3.Takubo K, et al. Regulation of the HIF-1alpha level is essential for hematopoietic stem cells.Cell Stem Cell. 2010;7(3):391-402. 4.Francesco Locatelli , et al. Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients. Am J Nephrol. 2017;45(3):187-99.  5.https://www.fiercepharma.com/pharma/astrazeneca-finally-drops-roxadustat-us-rights-after-fda-rejection-trial-failure.

SHENZHEN, CHINA, June 18, 2024 (GLOBE NEWSWIRE) -- Innovative drug Methylthioninium Chloride Enteric-coated Sustained-release Tablets (Lumeblue®) is an oral diagnostic drug, approved by China’s NMPA for enhancing visualisation of colorectal lesions in adult patients undergoing screening or surveillance colonoscopy. The results of the Phase III clinical trial in China show that the Product can significantly improve the detection rate of non-polypoid colorectal lesions (the primary endpoint of the study), leading to an improved detection rate of dangerous lesions such as non-polypoid adenomas (the secondary endpoint). The Product can be taken during the bowel preparation step, ensuring that colorectal staining is completed by the time colonoscopy is conducted. This not only enhances the detection rate of colorectal lesions but also potentially simplifies the colonoscopy procedure, making the examination more efficient and improving the screening benefits. As of now, CMS's newly launched innovative portfolio has been expanded to 5 products, continuously generating driving force to the Group’s sustainable and healthy development. China Medical System Holdings Limited (the “Company”, together with its subsidiaries, the “Group” or “CMS”) is pleased to announce that on 11 June 2024, the New Drug Application (NDA) of the Group’s innovative drug methylthioninium chloride enteric-coated sustained-release tablets (Lumeblue®) (the “Product”) has been approved by the National Medical Products Administration of China (NMPA). The drug registration certificate was obtained on 18 June 2024. The Product is indicated to enhancing visualisation of colorectal lesions in adult patients undergoing screening or surveillance colonoscopy, and it is the first oral methylthioninium chloride enteric-coated sustained-release tablets in China. The Group will synergize with existing gastroenterology products and resources to advance the commercialization and academic promotion related works of the Product in an orderly manner, aiming to achieve nationwide large-scale clinical application as soon as possible so as to benefit patients with colorectal disease. Lumeblue® is an oral diagnostic drug that uses patented multi-matrix (MMX) technology to deliver active substances directly to the colon and release them locally in a controlled manner. As an enhancer dye, the Product increases the contrast between colorectal lesions and healthy mucosa. The results of the Phase III clinical trial in China show that the Product can significantly improve the detection rate of non-polypoid colorectal lesions (the primary endpoint of the study), leading to an improved detection rate of dangerous lesions such as non-polypoid adenomas (the secondary endpoint)[1]. In addition, the Product can be taken during the bowel preparation step, ensuring that colorectal staining is completed by the time colonoscopy is conducted. This not only enhances the detection rate of colorectal lesions but also potentially simplifies the colonoscopy procedure, making the examination more efficient and improving the screening benefits. According to the diagnosis and treatment data of the Digestive Endoscopy Branch of the Chinese Medical Association, approximately a total of 28 million gastroenteroscopies were completed nationwide in 2012, including 5.83 million colonoscopies. In 2019, approximately 38.73 million gastroenteroscopies were completed nationwide, an increase of 34.62% compared with 2012[2]. The Chinese consensus of early colorectal cancer screening recommends that people aged 50 to 75 years old should be screened for colorectal cancer regardless of whether they have alarm symptoms[3]. There are approximately 400 million people aged 50 to 75 in China in 2020[4]. With the popularity of early screening for colorectal cancer in China, it is expected to witness a considerable growth of the number of colonoscopies in China in the future. The Product has been approved by the European Medicines Agency (EMA) to be commercialized in the European Union under the trade name Lumeblue™ in August 2020. The Group obtained an exclusive license for the Product from Cosmo Technologies Ltd, a fully owned subsidiary of Cosmo Pharmaceuticals NV, on 3 December 2020. Driven by the twin-wheel of "Collaborative R&D and Independent R&D", CMS has continuously deployed global first-in-class (FIC) and best-in-class (BIC) innovative products guided by patient and clinical demands. With enhancing R&D capabilities in developing differentiated innovative products, CMS has empowered the continuous transformation of scientific research outcomes into clinical application, continuously releasing the value of innovation. As of now, CMS's newly launched innovative portfolio has been expanded to 5 products, continuously generating driving force to the Group’s sustainable and healthy development. Desidustat Tablets and Methotrexate Injection (rheumatoid arthritis), CMS’s innovative pipeline products, are currently under NDA review in China. Meanwhile, over 10 innovative pipeline products are undergoing clinical trials in China, mainly randomized controlled trials (RCT). CMS is expected to launch differentiated innovative products every year in the future with higher efficiency and more controllable costs, continuing to optimize its product portfolio and build fresh driving forces for the mid- to long-term development of the Company. About CMS CMS is a platform company linking pharmaceutical innovation and commercialization with strong product lifecycle management capability, dedicated to providing competitive products and services to meet unmet medical needs. CMS focuses on the global first-in-class (FIC) and best-in-class (BIC) innovative products, and efficiently promotes the clinical research, development and commercialization of innovative products, enabling the continuous transformation of scientific research into clinical practices to benefit patients. CMS deeply engages in several specialty therapeutic fields, and has developed proven commercialization capabilities, extensive networks and expert resources, resulting in leading academic and market positions for its major marketed products. CMS continues to promote the in-depth development of its advantageous specialty fields and expand business boundaries. While strengthening the competitiveness of the cardio-cerebrovascular/gastroenterology business, CMS independently operates its dermatology and medical aesthetics business, and ophthalmology business, aiming to gain leading positions in specialty therapeutic fields, whilst enhancing the scale and efficiency. At the same time, CMS has expanded its business territory to the Southeast Asian market, striving to become a "bridgehead" for global pharmaceutical companies to enter the Southeast Asian market, further escorting the sustainable and healthy development of the Group. Reference: The results of the Phase III clinical trial in China was published and can be found at: The diagnosis and treatment data of the Digestive Endoscopy Branch of the Chinese Medical Association Chinese consensus of early colorectal cancer screening (2019, Shanghai)，Chinese Journal of Internal Medicine，DOI： 10.3760/cma.j.issn.0578-1426.2019.10.004 CHINA POPULATION CENSUS YEARBOOK 2020, can be found at： CMS Disclaimer and Forward-Looking Statements This press release is not intended to promote any products to you and is not for advertising purposes. This press release does not recommend any drugs, medical devices and/or indications. If you want to know more about the diagnosis and treatment of specific diseases, please follow the opinions or guidance of your doctor or other medical and health professionals. Any treatment-related decisions made by healthcare professionals should be based on the patient’s specific circumstances and in accordance with the drug package insert. This press release which has been prepared by CMS does not constitute any offer or invitation to purchase or subscribe for any securities, and shall not form the basis for or be relied on in connection with any contract or binding commitment whatsoever. This press release has been prepared by CMS based on information and data which it considers reliable, but CMS makes no representation or warranty, express or implied, whatsoever, and no reliance shall be placed on, the truth, accuracy, completeness, fairness and reasonableness of the contents of this press release. Certain matters discussed in this press release may contain statements regarding the Group’s market opportunity and business prospects that are individually and collectively forward-looking statements. Such forward-looking statements are not guarantees of future performance and are subject to known and unknown risks, uncertainties and assumptions that are difficult to predict. Any forward-looking statements and projections made by third parties included in this press release are not adopted by the Group and the Company is not responsible for such third-party statements and projections. Media Contact Brand: China Medical System Holdings Ltd. Contact: CMS Investor Relations Email: ir@cms.net.cn Website: Source: China Medical System Holdings Ltd.