肺癌是全球死亡率最高的癌症，据世界卫生组织国际癌症研究机构（IARC）发布的最新数据显示，2020年全球癌症死亡人数达996万，其中肺癌死亡人数约180万，占比约18%。在中国，肺癌的发病率和死亡率均列首位，且发病率呈逐年上升趋势^-1 。非小细胞肺癌（NSCLC）是肺癌最常见的组织学分型，约占肺癌患者的85%，其中又以非鳞状NSCLC的发病率最高^[3]。在NSCLC的治疗中，以PD-1/PD-L1为代表的免疫检查点抑制剂（ICI）发展迅速，抗PD-1单抗联合化疗已被美国国立综合癌症网络（NCCN）和中国临床肿瘤学会（CSCO）等指南推荐为非鳞状NSCLC的一线标准治疗方案^-1，H药针对该领域的治疗策略有望为患者提供更多治疗选择。

此次获受理主要基于一项比较H药联合化疗（卡铂-培美曲塞）与化疗（卡铂-培美曲塞）一线治疗晚期非鳞状非小细胞肺癌患者中的随机、双盲、多中心III期临床研究。研究结果显示，H药联合化疗对比化疗显著延长了无进展生存期（PFS），达到预设的优效标准，且安全性良好，未观察到新的安全性信号。

作为复宏汉霖首个自主研发的创新型单抗，H药聚焦肺癌和消化道肿瘤等高发癌种，并在全球开展10余项以H药为核心的免疫联合疗法临床研究，尤其在肺癌治疗领域，公司临床布局已全面覆盖肺癌一线治疗。其中，针对ES-SCLC，复宏汉霖于2022年在美国启动了一项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，以进一步支持H药在美国的上市申报，并且，H药联合化疗一线治疗ES-SCLC的上市申请也已获得欧盟EMA受理，有望于2024年上半年获得批准。此前，H药治疗小细胞肺癌（SCLC）已相继获得美国食品药品监督管理局（FDA）和欧盟委员会（EC）的孤儿药资格认定。在局限期小细胞肺癌（LS-SCLC）方面， H药联合化疗同步放疗一线治疗LS-SCLC的国际多中心III期临床研究也在积极推进中，目前已完成中国、美国、欧洲、澳大利亚等国家和地区的首例患者给药。

未来，复宏汉霖将继续以患者为核心，不断提升创研能力，推动产生更大的临床价值，为中国乃至全球患者提供更多优质、可及、可负担的产品和治疗方案。

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，2项适应症上市申请分别在中国和欧盟获受理，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）的上市申请也已获得欧盟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凯发期刊《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）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，在国际上市1款产品，19项适应症获批，3个上市申请分别获中国NMPA、美国FDA和欧盟EMA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创新中心，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，不断夯实一体化综合生产平台，其中，上海徐汇基地已获得中国和欧盟GMP认证，松江基地（一）也已获得中国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^®，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凯发市场。

The NDA for New Indication of Henlius Anti-PD-1 mAb Serplulimab in Combination with Chemotherapy for the First-line Treatment of non-squamous NSCLC Accepted by the NMPA

Shanghai, China, Dec. 12^th, 2023 – Shanghai Henlius Biotech, Inc. (2696.HK) announced that the NDA for new indication of HANSIZHUANG, serplulimab, an innovative anti-PD-1 mAb independently developed by the company, in combination with chemotherapy as a first-line treatment for patients with locally advanced or metastatic non-squamous non-small cell lung cancer (nsNSCLC) has been accepted by the National Medical Products Administration (NMPA), which is the fifth indication for HANSIZHUANG accepted by the NMPA. To date, HANSIZHUANG has been approved for the treatment of microsatellite instability-high (MSI-H) solid tumors, squamous non-small cell lung cancer (sqNSCLC) , extensive-stage small cell lung cancer (ES-SCLC) and esophageal squamous cell carcinoma (ESCC).

Lung cancer is the cancer with the highest global mortality rate. According to the latest data released by the International Agency for Research on Cancer (IARC) of the World Health Organization, the number of cancer deaths worldwide in 2020 reached 9.96 million, of which approximately 1.8 million died from lung cancer, accounting for 18%. In China, the incidence rate and mortality of lung cancer rank first, and the incidence rate is increasing year by year ^-1. The non-small cell lung cancer (NSCLC) is the most common histological type of lung cancer, accounting for about 85% of lung cancer patients, among which nsNSCLC has the highest incidence rate ^[3]. In the treatment of NSCLC, immune checkpoint inhibitors (ICI), such as PD-1/PD-L1, have developed rapidly, notably, the anti-PD-1 mAb plus chemotherapy has been recommended by the latest NCCN guidelines and CSCO guidelines as the first-line treatment for nsNSCLC^-1 ,?and serplulimab therefore is expected to bring a new option for patients.

The NDA for new indication of HANSIZHUANG is mainly based on a randomized, double-blind, multi-center phase 3 clinical study of HANSIZHUANG in combination with chemotherapy, or chemotherapy as a first-line treatment for patients with advanced non-squamous non-small cell lung cancer. The study results demonstrated that HANSIZHUANG in combination with chemotherapy significantly prolonged progression-free survival (PFS) compared with chemotherapy, which has met the pre-specified superiority criteria, with good safety and no detection of new safety signal.

HANSIZHUANG, Henlius’ first self-developed innovative monoclonal antibody, focuses on lung and gastrointestinal cancer and has initiated more than 10 clinical studies on immuno-oncology combination therapies worldwide. It covers the full range of first-line treatment of lung cancer, in which a head-to-head bridging trial of HANSIZHUANG versus first-line standard-of-care atezolizumab for ES-SCLC was launched in the U.S. in 2022, which is beneficial for its registration and commercialization in the U.S. In addition, the Marketing Authorization Application (MAA) for HANSIZHUANG on ES-SCLC has been validated by the European Medicines Agency (EMA), with approval expected in the first half of 2024. Previously, 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. Furthermore, Henlius is steadily advancing a global phase 3 multi-center clinical research of HANSIZHUANG for the limited stage small cell lung cancer (LS-SCLC) and its first patients in China, the U.S., Europe, and Australia have been dosed, respectively.?

In the future, Henlius will continue to improve its innovation capabilities to meet patients’ needs and create greater clinical value, aiming to provide more accessible, affordable, and high-quality products and solutions to patients around the world.

【参考文献】

[1] Sung H,Ferlay J,Siegel RL,Laversanne M,SoerjomataramI,Jemal A,Bray F.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin.2021 Feb 4.

[2] Cao W, Chen HD, Yu YW, Li N, Chen WQ.Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chin Med J (Engl). 2021;134(7):783-791.

[3] Schabath MB, Cote ML. Cancer Progress and Priorities: Lung Cancer. CancerEpidemiol Biomarkers Prev. 2019 Oct;28(10):1563-1579. doi:10.1158/1055-9965.EPI-19-0221.

[4] 《中国临床肿瘤学会（CSCO）非小细胞肺癌诊疗指南2023》

[5] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^® ) for Non-Small Cell Lung Cancer V.3.2023

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, 2?marketing applications?are?under review in China and?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 application?of the first-line treatment for ES-SCLC is?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, HANSIZHUANG 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 3?marketing applications have been accepted for review in China, 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.