2023-5年5月22日，成都-复宏汉霖（2696.HK）发表声明，有限公司自己研发团队的创新技术抗PD-1单抗H药——汉斯状®（通用的名：斯鲁利单抗注射器液）合力含氟尿嘧啶类和铂类口服药物应用于PD-L1阳型的不得切掉产品局部后期/反复病发或移转性食管鳞状人体血细胞系癌(ESCC)的带兵人的手术疗法新转变症的挂牌上市注册申请表申请表(NDA)荣获一个国家产品开展管理工作局换取许可，为食管鳞癌人群提拱了的手术疗法新使用。现已，H药已获准的手术疗法微遥感卫星较高不稳定性高(MSI-H)实体模型瘤、鳞状非小人体血细胞系肺良性肿瘤（sqNSCLC）和多方面期小人体血细胞系肺良性肿瘤（ES-SCLC）3项转变症。复宏汉霖不间断积极推进H药在肺良性肿瘤、代谢道良性肿瘤等方面的不一致性化、多向度合理布局，得以推动了人群荣获挺高收效。
复宏汉霖股东长兼连接股东张文杰
H药获准第4项适应性症应用于方法食管鳞癌，logo着是一款优质质量抗PD-1单抗使唤治的肠蠕动道良性肿癌行业层面介绍新渴望。自22年9月获准挂牌上市来，H药在监床实行中大面积谋福利肠蠕动道良性肿癌、非小细胞肺癌等行业层面朋友，牢固树立起良好的的性价比，并出现企业效果。未来的发展，企业将仍然引领H药好处和竟争力，推动H药股票市场户外拓展步法，为全球排名大量朋友带去可压力的多元化药。
复宏汉霖进行监事、顶尖进行官、总截兼顶尖账务官朱俊
以临床医学中药医疗需要为支撑，复宏汉霖发展肿癌天然免疫细胞靶向中药医疗邻域，聚焦点肿癌重點病种，深入开发H药多瘤种调整布局，乐观进行其在全球排名区间云同步开发的各项天然免疫细胞聯合中医疗法做实验的时候。圆满结束H药应用食管鳞癌，进那步认可了H药的中药医疗成长性，有力突显复宏汉霖的研制创新技术水准。期盼H药十年后的中国更加多乐观临床医学中药医疗最终的爆出，进那步惠及更具有广泛性的肿瘤患儿。
H药食管鳞癌Ⅲ期临床研究主要研究者、国内 医药学地理学校肿癌医生黄镜院士
食管鳞癌为食管癌中最为常见的病理类型，临床需求较大且总体预后相对较差。斯鲁利单抗围绕不能手术切除的局部晚期或转移性食管鳞癌开展了一项Ⅲ期临床研究（ASTRUM-007）并取得优异结果，该研究基于大样本量的本土人群数据，充分确证了斯鲁利单抗联合化疗一线治疗局部晚期/转移性、PD-L1阳性（PD-L1 CPS≥1）食管鳞癌患者，能够带来PFS、OS的显著获益，期待其在临床实践中惠及更多患者。
食管癌是全球第六大癌症死亡原因，也是我国的高发恶性肿瘤。统计显示，中国食管癌发病率和死亡率分别位列恶性肿瘤的第六和第四位，其中食管鳞癌为最常见的病理类型，约占中国所有食管癌病例的85.79%[1]。由于早期症状不明显，在我国约70%的患者确诊时已为局部晚期或转移性食管鳞癌，失去了手术治疗机会[2]。近年来，多项研究表明抗PD-1单抗联合化疗可为食管癌患者带来生存获益，免疫检查点抑制剂联合化疗已成为我国食管癌的一线治疗标准[3]。
此次获批主要基于一项随机、双盲、多中心的Ⅲ期临床研究（ASTRUM-007），旨在研究斯鲁利单抗对比安慰剂联合化疗（顺铂+5-FU）在既往未接受治疗、PD-L1阳性（PD-L1 CPS≥1）的晚期食管鳞癌患者中的疗效和安全性。根据世界著名学术讨论刊物Nature Medicine发表的ASTRUM-007临床研究结果显示，斯鲁利单抗联合化疗带来了总生存期（OS）和无进展生存期（PFS）的全面生存获益，并具备良好的安全性。值得注意的是，PD-L1高表达人群接受斯鲁利单抗联合化疗较意向性治疗（ITT）人群具有更大生存获益，在针对PD-L1 CPS≥10人群的分析中，斯鲁利单抗联合化疗组的中位OS长达18.6个月，较对照组绝对延长4.7个月，死亡风险降低41%。目前，ASTRUM-007学习成就已争相品牌发布于2022 ESMO Asia公司、2023 ASCO公司等全国学术界电视电话会议，获得了国.际学术性界角度承认。
包围H药，有限公司准确把握肺癌患者与肠蠕动道肺部肿瘤三大癌种，正极扎实推进H药与机构其它的企业产品的信息化甚至与科技创新治疗的连合，于全世界搜集抓好10麦克劳林公式恶性肿瘤免疫力聯合辽法临床治疗做实验的时候，累计到组逾3600名受试者，國际化的医学研究方案数据分析有希望为世界企业申报出具坚实支持力。真对转化道淋巴肿瘤，H药已应用MSI-H物理瘤适合症，而以MSI-H比较严重的结肠道癌和胃溃疡等患有带去调理愿。互相，该药在直肠癌新辅助工具的/辅助工具的个方面已進入Ⅲ期药学学习，即将使直肠癌客户在前线便从癌症免疫系统治疗中收效。1.1.肝癌行业领域，H药已应用sqNSCLC和ES-SCLC两种适于症，并为全球最大率先应用一专多能诊治小血细胞膜1.1.肝癌（SCLC）的抗PD-1单抗，有限公司亦进度表于2024年下大半年就H药一专多能诊治非鳞状非小血细胞膜1.1.肝癌（nsNSCLC）在中提交成功上市申报。与此直接，H药制疗SCLC再度收获了荷兰肉食品非处方药参与工作制度局（FDA）和欧盟委员会国家编委会会（EC）评为的遗孤药资证界定，该药中俄原油管道制疗ES-SCLC的欧盟委员会国家纳斯达克上市经营使用（MAA）早已于202四年1月收获澳洲非处方药工作制度局（EMA）业务办理，可能于2023年上一年后收获批准书。复宏汉霖亦在韩国的进行好几回项H药评测品牌规范方法阿替利珠单抗于ES-SCLC的头对头桥接耐压试验，策划于2023年在韩国的出具发售经营学生申请（BLA)。最后，复宏汉霖还稳步发展积极推动H药优越性期小上皮细胞肺腺癌（LS-SCLC）的中国多主Ⅲ期临床药学钻研。
工业服务开拓个方面，复宏汉霖对应性H药通过了超前意识性的空间页面布局，并不间断多要素、多推广方式优化该货品的可及性，到现如今，H药已受惠逾3.5万名我国患儿，并在我国镜内进行29个市县的招投标挂网，一起，已来到杭州市、程度市、温州市、深圳市、广东省、内蒙古回族自治权区等二十二个省/地市级个性型工业服务补整形稳定导航。对应性在俄罗斯贸易市面上，复宏汉霖与KGbio于今年确定联手，授于其H药首位单药的治疗方法及2项联手的治疗方法在东南方亚的地区10个國家的强势来袭研发和工业服务化财产权利；2026年9月，平台进两步就H药在中东地区北非区域划分1俩个國家的的强势来袭工业服务化财产权利授于KGbio。不仅而且，平台还授于HAHA体育
国药H药在俄罗斯贸易市面上的强势来袭工业服务化财产权利，一体化开拓H药的在俄罗斯贸易市面上空间页面布局，倾力覆盖住全世界更诸多的患儿目标群体。
的前景，复宏汉霖将持继上升研产销量全产链总体有实力，发展精准扶贫治愈与转变研究分析的治愈体系建设，多关键点实行H药临床检验價值，持继塑造癌症免疫抗体治愈新标竿，为世界各国自身带去关注与可能。
H药 汉斯状®为重组人源化抗PD-1单抗注射液（通用名：斯鲁利单抗注射液），是全球首个获批一线治疗小细胞肺癌的抗PD-1单抗，目前已有4项适应症获批上市，1项适应症上市申请在欧盟获受理，10余项临床试验同步在全球开展。
2022年3月，H药正式获批上市，目前可用于治疗微卫星高度不稳定（MSI-H）实体瘤、鳞状非小细胞肺癌（sqNSCLC）、广泛期小细胞肺癌（ES-SCLC）及食管鳞状细胞癌（ESCC）。H药联合化疗一线治疗广泛期小细胞肺癌（ES-SCLC）的上市申请也获得欧盟EMA受理。聚焦肺癌和消化道肿瘤，复宏汉霖积极推进H药与公司其他产品的协同以及与创新疗法的联合，相继获得中国、美国、欧盟等国家及地区的临床试验许可，在全球同步开展10余项肿瘤免疫联合疗法临床试验。截至目前，H药已于中国、美国、土耳其、波兰、格鲁吉亚等国家和地区累计入组超3600人，其中2项国际多中心临床试验入组白人的比例超过30%，是拥有国际临床数据较多的抗PD-1单抗之一。H药的3项关键性临床研究结果分别发表于知名期刊《美国医学会杂志》（JAMA）、《自然-医学》（Nature Medicine）和British Journal of Cancer。此外，H药还荣获《CSCO 小细胞肺癌诊疗指南》、《CSCO 非小细胞肺癌诊疗指南》、《CSCO 食管癌诊疗指南》、《CSCO 结直肠癌诊疗指南》、《CSCO 免疫检查点抑制剂临床应用指南》和《中国食管癌放射治疗指南》等多部权威指南推荐，为肿瘤临床诊疗提供重要参考。海外方面，H药治疗SCLC也已获得美国FDA和欧盟EC的孤儿药资格认定，并在美国启动了一项H药对比一线标准治疗阿替利珠单抗用于ES-SCLC的头对头桥接试验。
复宏汉霖（2696.HK）也是家國际化的技术革新动物化工司，迫切需要打造于为世界各国求美者打造可的负担的高品格动物药，品牌合并癌肿、自己天然免疫症状、护眼症状等范畴，已在国家发行5款品牌，在國际发行1款品牌，19项不适应症获准，2发行办理差别获荷兰FDA和欧盟委员会委员会EMA结案。自20十多年成为今年以来，复宏汉霖已建造立体式化动物化工软件网站，有效及技术革新的专业化核心思想专业能力包括产品研发、产出及商业运作营运全产业化链。司已建立联系健全完善有效的世界各国技术革新心中，遵循國际进口药品产出质的管理规程（GMP）规格采取产出和质监督控制，逐渐夯实基层基础立体式化全方位的产出软件网站，这之中，北京徐汇机地已换取国家和欧盟委员会委员会GMP认真，松江机地（一）也已换取国家GMP认真。
复宏汉霖前瞻性布局了一个多元化、高质量的产品管线，涵盖20多种创新单克隆抗体，并全面推进基于自有抗PD-1单抗H药 汉斯状®的肿瘤免疫联合疗法。继国内首个生物类似药汉利康®（利妥昔单抗）、中国首个自主研发的中欧双批单抗药物汉曲优®（曲妥珠单抗，欧洲商品名：Zercepac®，澳大利亚商品名：Tuzucip®和Trastucip®）、汉达远®（阿达木单抗）和汉贝泰®（贝伐珠单抗）相继获批上市，创新产品汉斯状®（斯鲁利单抗）已获批用于治疗微卫星高度不稳定（MSI-H）实体瘤、鳞状非小细胞肺癌、广泛期小细胞肺癌和食管鳞状细胞癌，并成为全球首个获批一线治疗小细胞肺癌的抗PD-1单抗。公司亦同步就16个产品在全球范围内开展30多项临床试验，对外授权全面覆盖欧美主流生物药市场和众多新兴市场。
Henlius' Novel Anti-PD-1 mAb HANSIZHUANG (Serplulimab) Approved for the Treatment of ESCC
Shanghai, China, Sep 22nd, 2023 – Shanghai Henlius Biotech, Inc. (2696. HK) announced that the new drug application (NDA) for new indication of HANSIZHUANG (serplulimab injection), an innovative anti-PD-1 monoclonal antibody independently developed by the company, in combination with drugs containing fluorouracil and platinum for the first-line treatment of patients with PD-L1 positive unresectable locally advanced/recurrent or metastatic esophageal squamous cell carcinoma (ESCC), has been approved by the National Medical Products Administration (the "NMPA"), providing a new treatment option for patients with ESCC. Up to date, HANSIZHUANG has been approved for the treatment of microsatellite instability-high (MSI-H) solid tumors, squamous non-small cell lung cancer (sqNSCLC), and extensive stage small cell lung cancer (ES-SCLC). To further benefit patients, Henlius continues to differentiate and optimize product portfolios and the roadmap of HANSIZHUANG in lung cancer, gastrointestinal cancer, and other cancers.
Wenjie Zhang, Chairman, and Executive Director of Henlius, remarked, "ESCC is the fourth approved indication of HANSIZHUANG and its approval signifies that this high-quality anti-PD-1 mAb offers a new ray of hope for the treatment of difficult-to-treat gastrointestinal cancer. Since it launched in March 2022, HANSIZHUANG has benefited a wide range of patients with lung cancer, gastrointestinal cancer, and other tumors, further solidifying its positive reputation with a strong brand effect. Moving forward, we will continue leveraging the strengths of HANSIZHUANG and fully tapping its potential to accelerate market expansion to provide affordable, innovative treatments to more patients worldwide."
Jason Zhu, Executive Director, Chief Executive Officer, President and Chief Financial Officer of Henlius, said, "Henlius is driven by unmet clinical needs and has devoted itself to precision immunotherapy for tumors. We are focusing on major cancer types, steadily expanding the clinical layout of HANSIZHUANG in multiple cancer types, and actively initiating immune combination therapy trials worldwide. The approval of ESCC further validates the potential of HANSIZHUANG and demonstrates the innovation capabilities of Henlius. We look forward to more positive study results of HANSIZHUANG to make further contributions to cancer treatment for more cancer patients."
Prof. Jing Huang, the leading principal investigator of ASTRUM-007, from Cancer Hospital Chinese Academy of Medical Sciences, said, "ESCC is the most common pathological type of esophageal cancer with high clinical demand and relatively poor overall prognosis. The phase 3 clinical study (ASTRUM-007) on serplulimab plus chemotherapy for unresectable locally advanced/metastatic esophageal cancer achieved promising results, which was conducted on a large sample of the local population and fully demonstrated that serplulimab in combination with chemotherapy as a first-line treatment for locally advanced/metastatic and PD-L1 positive (PD-L1 CPS≥1) esophageal cancer patients can significantly improve progression-free survival (PFS) and overall survival (OS). We are hoping that serplulimab will benefit more patients in clinical practice."
Providing a new solution for urgent clinical needs
Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide as well as a prevalent malignant tumor in China. According to the data, the incidence and mortality of esophageal cancer rank sixth and fourth, respectively, among all malignant tumors in China, of which ESCC is the most common pathological type that accounts for about 85.79% of all esophageal cancer cases[1]. As the symptoms of early esophageal cancer are often subtle, about 70% of patients are diagnosed at mid-to-late stage, missing out on surgical treatment[2]. In recent years, many studies have shown that anti-PD-1 mAb combined with chemotherapy can bring survival benefits to patients with esophageal cancer. Up to date, immune checkpoint inhibitor combined with chemotherapy has become the standard first-line treatment for advanced esophageal cancer in China[3].
The approval was primarily based on ASTRUM-007, a randomized, double-blind, multicenter, phase 3 study aiming to compare the efficacy and safety of serplulimab versus placebo in combination with chemotherapy (5-FU + cisplatin) in patients with previously untreated, PD-L1–positive (PD-L1 CPS≥1), advanced ESCC. According to the study results published in the international leading journal Nature Medicine, serplulimab in combination with chemotherapy significantly improved progression-free survival (PFS) and overall survival (OS), its safety was also manageable. Notably, the PD-L1 high-expression group receiving serplulimab combined with chemotherapy gained a greater survival benefit comparing to the intention-to-treat (ITT) group, in the analysis of the group with PD-L1 CPS≥10, the combination of serplulimab and chemotherapy group had a median OS of 18.6 months, with an absolute extension of 4.7 months compared to the control group and a 41% reduction in the risk of death. The results of ASTRUM-007 have been released at many world-class conferences, such as the 2022 ESMO Asia Congress and the 2023 ASCO Annual Meeting, receiving high recognition from the international academic community.
Widening indication coverage for patients worldwide
Henlius focuses on lung and gastrointestinal cancer and promotes the synergy of HANSIZHUANG with innovative therapies, in which more than 10 clinical trials on immuno-oncology combination therapies have been initiated worldwide. As of now, the company has enrolled more than 3,600 subjects, and the global clinical research data will provide strong support for its NDAs in overseas markets. In terms of gastrointestinal cancer, HANSIZHUANG has been approved for the treatment of MSI-H solid tumours, which brings hope to patients with MSI-H colorectal cancer and MSI-H gastric cancer. Furthermore, HANSIZHUANG has led the way with a phase 3 clinical study on neoadjuvant/adjuvant therapies for gastric cancer, striving to benefit gastric cancer patients from the early line of immunotherapy. In the field of lung cancer, HANSIZHUANG has been approved for sqNSCLC and ES-SCLC, making it the world's first anti-PD-1 mAb for the first-line treatment of SCLC. The company also plans to submit a marketing application for HANSIZHUANG as a first-line treatment for non-squamous non-small cell lung cancer (nsNSCLC) in China in the second half of 2023. In addition, HANSIZHUANG was also granted orphan drug designations by the U.S. Food and Drug Administration (FDA) and European Commission (EC) for the treatment of SCLC, and its Marketing Authorization Application (MAA) for the first-line treatment of ES-SCLC was validated by the European Medicines Agency (EMA) in March 2023, with the expectation of approval in the first half of 2024. Henlius also lanuched a head-to-head bridging trial of HANSIZHUANG versus first-line standard-of-care atezolizumab for ES-SCLC in the U.S. and the company plans to submit a Biologics License Application (BLA) for HANSIZHUANG in the U.S. in 2024. Furthermore, Henlius is steadily advancing a global multi-center clinical research of HANSIZHUANG for the limited stage small cell lung cancer (LS-SCLC).
Henlius proactively promotes the commercialization of HANSIZHUANG to enhance its accessibility through multiple dimensions and channels. Up to date, HANSIZHUANG has benefited over 37,000 Chinese patients and has completed the tendering process on the procurement platform in 29 provinces in Chinese mainland and was included into the customized commercial medical insurance directory in 26 Provinces and cities such as Shanghai, Chengdu, Ningbo, Xiamen, Fujian, Ningxia Hui Autonomous Region, etc. For the overseas market, Henlius forged a partnership with Kalbe Genexine Biologics (KGbio) to grant it an exclusive license to develop and commercialize HANSIZHUANG in relation to its first monotherapy and two combination therapies in 10 Southeast Asian countries. In August 2023, the company further granted KGbio exclusive development and commercialization authorizations of HANSIZHUANG in 12 Middle East and North Africa (MENA) countries. In addition, Henlius entered into an exclusive license agreement with Fosun Pharma for the commercialization of HANSIZHUANG in the U.S., aiming to expand the overseas market layout of HANSIZHUANG and reach out to a wider range of global patients.
In the future, Henlius will continue to enhance its capabilities in innovation, manufacturing, and commercialization, dedicating its efforts to the development of a system for precision treatment and translational medicine research and maximizing the clinical value of HANSIZHUANG to set the pace in tumor immunotherapy to deliver warmth and hope to patients all over the globe.
【借鉴医学文献】
[1] Chen R, Zheng R, Zhang S, et al. Patterns and trends in esophageal cancer incidence and mortality in China: an analysis based on cancer registry data[J]. Journal of the National Cancer Center, 2023.
[2] 王天云, 张瑜, 徐泳, 卢铀, & 彭枫. (2018). 胆襄癌食管鳞癌爱美者四线肺癌晚期化疗药用价值及长期生存剖析. 北京省治癌行业行业协会网站老人癌肿中药治疗专委会第三个次学界公司暨北京省治癌行业行业协会网站治癌中成药专业理事会会第1次学界公司. 北京省治癌行业行业协会网站.
[3] 食管癌医疗规范（22年版）. 中国有祖国卫生学营养常务联合会.
HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first anti-PD-1 mAb for the first-line treatment of SCLC. Up to date, 4 indications are approved for marketing in China, 1 marketing application is under review in the EU, and more than 10 clinical trials are ongoing across the world.
HANSIZHUANG was launched in March 2022 and has been approved by the NMPA for the treatment of MSI-H solid tumours, squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC). Its marketing applications of the first-line treatment for ES-SCLC are under review by the EMA. Focusing on lung and gastrointestinal cancer, the synergy of HANSIZHUANG with in-house products of the company and innovative therapies are being actively promoted. It has successively obtained clinical trial approvals in China, the U.S., the EU and other countries and regions to initiate more than 10 clinical trials on immuno-oncology combination therapies in a wide variety of indications. As of now, the company has enrolled more than 3,600 subjects in China, the U.S., Turkey, Poland, Georgia and other countries and regions, and the proportion of White is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The results of 3 pivotal trials of HANSIZHUANG were published in the Journal of the American Medical Association (JAMA), Nature Medicine and the British Journal of Cancer, respectively. Furthermore, HASIZHUANG was recommended by the CSCO Guidelines for Small Cell Lung Cancer, the CSCO Guidelines for Non-Small Cell Lung Cancer, the CSCO Guidelines for Esophageal Cancer, the CSCO Guidelines for Colorectal Cancer, the CSCO Clinical Practice Guidelines on Immune Checkpoint Inhibitor, the China Guidelines for Radiotherapy of Esophageal Cancer, and other definitive guides, providing valuable references for clinical diagnosis and treatment of tumours. On the other hand, serplulimab was granted orphan drug designations by the U.S. FDA and the EC for the treatment of SCLC, and its bridging head-to-head trial in the United States to compare HANSIZHUANG to standard of care atezolizumab (anti-PD-L1 mAb) for the first-line treatment of ES-SCLC is well under way.
Henlius (2696.HK) is a global biopharmaceutical company with the vision to offer high-quality, affordable, and innovative biologic medicines for patients worldwide with a focus on oncology, autoimmune diseases, and ophthalmic diseases. Up to date, 5 products have been launched in China, 1 has been approved for marketing in overseas markets, 19 indications are approved worldwide, and 2 marketing applications have been accepted for review in the U.S., and the EU, respectively. Since its inception in 2010, Henlius has built an integrated biopharmaceutical platform with core capabilities of high-efficiency and innovation embedded throughout the whole product life cycle including R&D, manufacturing and commercialization. It has established global innovation centers and Shanghai-based manufacturing facilities in line with global Good Manufacturing Practice (GMP), including Xuhui Plant certificated by China and the EU GMP and Songjiang First Plant certificated by China GMP.
Henlius has pro-actively built a diversified and high-quality product pipeline covering over 20 innovative monoclonal antibodies (mAbs) and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as backbone. Apart from the launched products HANLIKANG (rituximab), the first China-developed biosimilar, HANQUYOU (trastuzumab for injection, trade name in Europe: Zercepac®; trade names in Australia: Tuzucip® and Trastucip®), the first China-developed mAb biosimilar approved both in China and Europe, HANDAYUAN (adalimumab) and HANBEITAI (bevacizumab), the innovative product HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumors, squamous non-small cell lung cancer (sqNSCLC) and extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC), making it the world's first anti-PD-1 mAb for the first-line treatment of SCLC. What's more, Henlius has conducted over 30 clinical studies for 16 products, expanding its presence in major markets as well as emerging markets.
