H药汉斯状®获批上市：复宏汉霖首款创新PD-1单抗 | 新闻稿

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关键词：上市获批

资讯来源：研发客

发布时间： 2022-03-27

2022年3月25日，上海——复宏汉霖（2696.HK）宣布，旗下首款自主研发的创新生物药PD-1抑制剂H药——汉斯状^®（通用名：斯鲁利单抗注射液）正式获得国家药品监督管理局（NMPA）批准，用于经既往标准治疗失败的、不可切除或转移性微卫星高度不稳定（MSI-H）的成人晚期实体瘤适应症，为患者提供治疗新选择，也为国内肿瘤精准免疫治疗赋能添势，助力推进中国生物医药行业高质量发展。

复宏汉霖董事长、执行董事兼首席执行官张文杰表示：“ 非常高兴看到H药汉斯状^®的首个适应症在中国获批，作为国内首批率先开启‘泛癌种’治疗MSI-H实体瘤的PD-1抑制剂，汉斯状^®将在临床实践中充分发挥自身优势，助力延长患者高质量生存期，推进肿瘤免疫治疗加速发展。H药是公司第5个上市的产品，作为创新升级的重大成果将进一步推动公司向Biopharma进化，促进更多以患者需求为核心的创新产出。”

H药汉斯状^®关键性II期临床研究主要联合研究者、南京金陵医院肿瘤中心秦叔逵教授表示：“ 以PD-1抑制剂为代表的免疫检查点抑制剂已在众多疾病领域展开了积极的探索，并在多个肿瘤治疗领域取得了突破性的进展。汉斯状^®针对MSI-H实体瘤的临床研究数据优异，相信能够积极改善临床疗效，为中国肿瘤精准治疗提供新思路和新选择。”

H药汉斯状^®关键性II期临床研究主要联合研究者、上海同济大学附属东方医院肿瘤科李进教授指出：“ 汉斯状^®的获批上市给MSI-H实体瘤患者带去了新希望，更好地满足肿瘤临床治疗用药需求，该产品在推动国内肿瘤治疗发展的同时，对于提升‘泛癌种’治疗认知及推动肿瘤精准免疫治疗发展起到了积极的作用。”

“泛癌种” 治疗惠及更广泛患者

此次获批主要是基于一项单臂、多中心、关键性II期临床研究，该试验的主要终点为独立影像评估委员会（IRRC）依据RECIST v1.1标准评估的客观缓解率（ORR）。截止到2021年7月10日，本试验共入组108名患者，其中68名经中心实验室或研究中心确认MSI-H的患者被纳入主要疗效分析人群。主要疗效分析人群中，经IRRC评估的ORR为39.7%（95%CI：28.03，52.30; 3例完全缓解，24例部分缓解）。研究结果表明，H药单药治疗既往标准治疗失败的、不可切除或转移性MSI-H实体瘤获益显著，达到预设的主要终点标准，且具有良好的安全性和耐受性。该项临床试验结果以口头汇报形式于第24届全国临床肿瘤学大会暨2021年CSCO学术年会上首次发布。

“微卫星 (Microsatellite)” 是基因中的一类短串联重复DNA序列，在DNA复制时插入或缺失引起微卫星序列长度的改变，被称为微卫星不稳定（Microsatellite Instability, MSI）^[1] 。大量研究表明，MSI与肿瘤的发生密切相关，在临床实践中，MSI已成为部分实体瘤预后和制定辅助治疗方案的重要生物标志物。在MSI的分类中，2种或2种以上位点改变被称为微卫星高度不稳定(MSI-H)，常见于子宫内膜癌、结直肠癌、胃癌等癌症，此类患者通常对于免疫检查点抑制剂有较高的应答率^[2-3]，PD-1/PD-L1作为重要的免疫抑制分子对于MSI-H特征型实体瘤患者具有较好的治疗效果。据统计，中国每年新发MSI-H肿瘤患者逾30万^[4]，其中部分患者缺乏有效治疗，并且，目前我国鲜有针对MSI-H晚期实体瘤获批的PD-1抑制剂，临床治疗需求远未被满足。H药的“横空出世”为国内治疗该适应症再添“利器”，将在实际临床中以独特的创新和高品质提升肿瘤临床诊疗能力，实现患者获益最大化，推动构建肿瘤防治体系建设。

国际品质助力海外市场布局

围绕H药，复宏汉霖已在全球开展并加速推进多元化的肿瘤免疫联合疗法，广泛覆盖肺癌、食管癌、头颈癌和胃癌等高发癌种，全面覆盖肺癌一线治疗。截至目前，H药全球累计入组超2800受试者，是拥有国际临床数据较多的PD-1抑制剂之一，为未来在全球范围内的上市注册申请打下扎实基础。值得一提的是，该产品针对鳞状非小细胞肺癌（sqNSCLC）和广泛期小细胞肺癌（ES-SCLC）的两项国际多中心III期临床试验在中国、土耳其、波兰、格鲁吉亚等国家和地区先后开设了研究中心，入组的高加索人群占比超30%，为临床研究提供了更全面的病例数据。其中治疗局部晚期或转移性sqNSCLC的NDA已获NMPA受理，有望今年获批上市。H药联合化疗一线治疗ES-SCLC的国际多中心III期研究已达到主要终点总生存期（OS），公司计划于2022年在中国及欧盟递交该适应症的上市注册申请，H药有望成为全球首个一线治疗SCLC的PD-1抑制剂。

在开展国际多中心临床研究的同时，复宏汉霖也在积极规划H药的海外商业化布局。早在2019年公司即与PT Kalbe Genexine Biologics（KG Bio）达成合作，授予其H药首个单药疗法及两项联合疗法在东南亚地区10个国家的独家开发和商业化权利。接下来，公司将携手更多商业合作伙伴，稳健持续拓展H药的海外布局，以优质的国际品质走上世界PD-1的舞台。

未来，复宏汉霖将持续以患者需求为核心，凭借高效及创新的自主核心能力持续推进更多汉霖“质”造，为中国乃至全球患者提供最高品质的药物和服务，打造生物制药领域民族品牌。

关于 H药汉斯状^®

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），是复宏汉霖首个自主研发的创新型单抗，该产品已获批用于治疗微卫星高度不稳定（MSI-H）实体瘤。围绕H药，复宏汉霖积极推进其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9项肿瘤免疫联合疗法临床试验，广泛覆盖肺癌、食管癌、头颈癌和胃癌等适应症，全面覆盖肺癌一线治疗。截至目前，H药已于中国、土耳其、波兰、格鲁吉亚等国家和地区累计入组超2800人，其中2项国际多中心临床试验入组高加索人种的比例超过30%，是拥有国际临床数据较多的抗PD-1单抗之一。H药联合化疗治疗局部晚期或转移性鳞状非小细胞肺癌（sqNSCLC）的NDA已获得NMPA受理，有望今年获批。H药联合化疗一线治疗广泛期小细胞肺癌（ES-SCLC）的国际多中心III期研究达到主要终点总生存期（OS），公司计划于2022年在中国及欧盟递交该适应症的上市注册申请，有望成为全球首个一线治疗SCLC的抗PD-1单抗。

关于复宏汉霖

复宏汉霖（2696.HK）是一家国际化的创新生物制药公司，致力于为全球患者提供可负担的高品质生物药，产品覆盖肿瘤、自身免疫疾病、眼科疾病等领域，已在中国上市5款产品，在欧盟上市1款产品，13项适应症获批，1个上市注册申请获得中国药监局受理。自2010年成立以来，复宏汉霖已建成一体化生物制药平台，高效及创新的自主核心能力贯穿研发、生产及商业运营全产业链。公司已建立完善高效的全球研发中心，按照国际药品生产质量管理规范（GMP）标准进行生产和质量管控，位于上海徐汇的生产基地已获得中国和欧盟GMP认证。

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^®）、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，其鳞状非小细胞肺癌适应症的上市注册申请也正在审评中。公司亦同步就12个产品、9个免疫联合治疗方案在全球范围内开展20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 Receives NMPA Approval for its First Innovative Monoclonal Antibody HANSIZHUANG

Shanghai, China, March 25^th, 2022 – Shanghai Henlius Biotech, Inc. (2696. HK) announced that its first self-developed innovative PD-1 inhibitor HANSIZHUANG (generic name: serplulimab injection) has been approved by the National Medical Products Administration (NMPA) for the treatment of adult patients with advanced unresectable or metastatic MSI-H (Microsatellite Instability-High) solid tumors that have failed to respond to previous standard treatments, providing an alternative treatment option for patients. Furthermore, it also empowers the domestic precision immunotherapy for tumors and promotes the high-quality development of China's biopharmaceutical industry.

Zhang Wenjie, Chairman, Executive Director, and CEO of Henlius, said, "I'm very glad to see the first indication of HANSIZHUANG was approved in China. As one of the pioneering PD-1 inhibitors for the 'pan-cancer' treatment of MSI-H solid tumors in China, HANSIZHUANG would give full play to its advantages in clinical practice to enable patients to live longer with more comfortable lives and accelerate the development of tumor immunotherapy. In addition, HANSIZHUANG is the fifth product launched by Henlius as well as a significant milestone in the company’s evolution toward Biopharma, which will actively drive Henlius to move forward, and inspire more innovative achievements centered on patient needs."

Professor Qin Shukui, one of the co-leading principal investigators of the pivotal phase II clinical study of HANSIZHUANG on MSI-H solid tumors, from the Tumor Center of Nanjing Jinling Hospital, said, "PD-1 inhibitor is one of the immune checkpoint inhibitors that has been explored in some diseases, which makes breakthroughs in many tumor treatments. The clinical research data of HANSIZHUANG for MSI-H solid tumors is outstanding and will actively improve the clinical efficacy and provide a new mindset and alternative option for the precision treatment for tumors in China."

Professor Li Jin, another co-leading principal investigator of the pivotal phase II clinical study of HANSIZHUANG on MSI-H solid tumors, from the Department of Oncology, Shanghai East Hospital, Tongji University, mentioned, "the approval of HANSIZHUANG brings new hope to patients with MSI-H solid tumors and better meets the demand of clinical treatment and medication of tumors. While promoting the development of domestic tumor treatment, this product plays a positive role in enhancing the recognition of 'pan-cancer' treatment and promoting the development of tumor precision immunotherapy."

"Pan-cancer" treatment benefits a broader patient population

The approval is mainly based on a single-arm, multi-center, pivotal phase II clinical study. The primary efficacy endpoint was objective response rate (ORR) assessed by independent radiological review committee (IRRC) per RECIST v1.1. As of July 10, 2021, 108 patients were enrolled, in which 68 patients with MSI-H confirmed by central laboratory or study sites were included in the main efficacy analysis population (MEAP). IRRC assessed ORR were 39.7% (95% CI: 28.03, 52.30; 3 CR, 24 PR) in MEAP. The study concludes that HANSIZHUANG monotherapy could bring significant benefits in the treatment of unresectable or metastatic MSI-H solid tumors that have failed to respond to previous standard treatments, met the primary endpoint criteria, and had good safety and tolerability. The results of this clinical study were first presented in oral at the 24th annual meeting of Chinese Society of Clinical Oncology (CSCO).

"Microsatellite" is a class of short tandem repeat DNA sequence in genes. It is called microsatellite instability (MSI) due to the change of microsatellite sequence length caused by insertion or deletion during DNA replication ^[1]. Many studies have shown that MSI is closely related to tumorigenesis, so in clinical practice, MSI is an important biomarker reference for the prognosis of some solid tumors and adjuvant treatment plans. MSI-H is one of the MSI types, in which two or more spots change, and commonly found in endometrial cancer, colorectal cancer, and gastric cancer, etc. These patients usually have high response to immune checkpoint inhibitors ^[2-3]. PD-1/PD-L1, important immunosuppressive molecules, have good therapeutic effect for patients with MSI-H solid tumors. It is estimated that there are more than 300,000 new MSI-H tumor patients in China every year^[4], and some of them have no access to effective treatment. Furthermore, there are few PD-1 inhibitors approved for MSI-H advanced solid tumors in China currently. The clinical treatment demand is far from being met. Therefore, the advent of HANSIZHUANG is a "weapon" for the treatment of MSI-H solid tumors in China. It is expected to enhance the clinical diagnosis and tumor treatment with unique innovation and superior quality in clinical practice to achieve maximum benefit for patients and promote the construction of tumor prevention and treatment system.

Leverage the world-class quality to explore overseas market

With HANSIZHUANG as the backbone, Henlius conducts and accelerates various clinical trials with immuno-oncology combination therapies worldwide in a wide variety of high-incidence solid tumors, including lung cancer (LC), esophageal carcinoma, head and neck carcinoma, gastric cancer, etc., and covering the full range of first-line treatments of lung cancers. Up to date, more than 2,800 subjects have been enrolled worldwide for HANSIZHUANG clinical trials, which makes it a PD-1 inhibitor with one of the largest global clinical data pools and lays a solid foundation for future applications across the world. On the other hand, two global multi-center phase III clinical trials regarding sqNSCLC and ES-SCLC are conducted in China, Turkey, Poland, Georgia and other countries and regions, in which the Caucasian accounts for more than 30% of the total enrolled subjects, providing more diverse cases for clinical research. The NDA of the treatment for locally advanced or metastatic squamous non-small cell lung cancer (sqNSCLC) has been accepted by the NMPA and is expected to be approved in 2022. The global multi-center phase III study of HANSIZHUANG in combination with chemotherapy for the first-line treatment of ES-SCLC met the primary study endpoint of the overall survival (OS) with remarkable readouts. Its NDA in China and MAA in the EU are expected to be filed in 2022, making HANSIZHUANG potentially the world’s first PD-1 inhibitor for the first-line treatment of SCLC.

Henlius actively explores overseas commercialization of HANSIZHUANG, while proceeding its global multi-center clinical research. As early as 2019, the company forged a partnership with PT Kalbe Genexine Biologics（KG Bio）to grant it an exclusive license to develop and commercialize HANSIZHUANG in relation to a monotherapy and two combination therapies in 10 Southeast Asian countries. Going forward, Henlius will continue to expand global commercialization layout of HANSIZHUANG to reach out to more countries and regions, which urges this product to step on to the world PD-1 stage and benefits a broader patient population worldwide with its world-class quality.

In the future, Henlius will keep focusing on patient needs and inspire more "made-by-Henlius" products with efficient and innovative in-house capabilities, aiming to provide highest quality solutions and services for patients in China and across the world and to build a national brand in biopharmaceutical industry.

参考文献

[1] Thibodeau S N, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon[J]. Science, 1993, 260(5109): 816-819.

[2] Michael J Overman, Ray McDermott, Joseph L Leach, et al. Nivolumab in patients with metastatic DNA mismatch repair deficient/microsatelliteinstability-high colorectal cancer (CheckMate 142): results of an open-label,multicenter, phase 2 study[J]. Lancet Oncology, 2017,18(9):1182-1191.

[3] Aurelien Marabelle, Dung T Le, Paolo A Asciert, et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase IIKEYNOTE-158 Study[J]. J Clin Oncol, 2020, 38(1): 1-10.

[4] Chen, W., et al., Cancer statistics in China, 2015. CA Cancer J Clin, 2016.

About HANSIZHUANG

HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first innovative monoclonal antibody developed by Henlius. It is approved by the NMPA for the treatment of MSI-H solid tumors. Henlius actively promotes HANSIZHUANG in conjunction with in-house products of the company and innovative therapies. It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 9 clinical trials on immuno-oncology combination therapies of HANSIZHUANG worldwide in a wide variety of indications, such as lung cancer, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc., and covering the full range of first-line treatments of lung cancers. Up to date, the company has enrolled more than 2,800 subjects in China, Turkey, Poland, Georgia and other countries and regions, and the proportion of Caucasian is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The NDA of the treatment for squamous non-small cell lung cancer (sqNSCLC) has been accepted by the NMPA and is expected to be approved in 2022. Furthermore, the global multi-center phase 3 clinical study of HANSIZHUANG in combination with chemotherapy in previously untreated extensive small-cell lung cancer (ES-SCLC) met the primary endpoint of overall survival (OS) with remarkable readouts and its NDA in China and MAA in the EU are expected to be filed in 2022, making this product potentially the world’s first anti-PD-1 mAb for the first-line treatment of SCLC.

About Henlius

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 in European, 13 indications approved worldwide, and 1 New Drug Application (NDA) accepted for review in China. 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 a Shanghai-based manufacturing facility certificated by China and the EU Good Manufacturing Practice (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, Zercepac^® in Europe), 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 and its NDA for the treatment of squamous non-small cell lung cancer is under review. What's more, Henlius has conducted over 20 clinical studies for 12 products and 9 combination therapies worldwide, expanding its presence in major market as well as emerging market.

联系方式

媒体：PR@Henlius.com

投资者：IR@Henlius.com