乳腺癌是全球女性发病率和死亡率最高的癌症，据GLOBOCAN数据显示，2022年全球乳腺癌新发病例达230万^[1]。其中，HER2阳性乳腺癌约占全部乳腺癌的20%-25%^[2]。另一方面，胃癌患者的HER2过表达比率约为12%-23%^[3]。曲妥珠单抗是治疗HER2阳性乳腺癌和胃癌的基石药物。

汉曲优^®为复宏汉霖按照中国、欧盟和美国等生物类似药相关法规开发和生产的曲妥珠单抗，用于治疗HER2阳性早期乳腺癌、转移性乳腺癌和转移性胃癌。2020年7月和8月，汉曲优^®先后获欧盟委员会（EC）和中国药品监督管理局（NMPA）批准于欧盟和中国上市。2024年4月，汉曲优^®获得美国食品药品监督管理局（FDA）批准上市，成为中美欧三批的“中国籍”单抗生物类似药，为其全球商业化进程增添了浓墨重彩的一笔。

复宏汉霖积极推动汉曲优^®的国际化商业布局，并携手全球商业合作伙伴Accord、Abbott、Eurofarma和KGbio等国际一流的生物制药企业，全面进军欧美主流生物药市场，并加快落子新兴市场。截止目前，该产品对外授权已覆盖约100个国家和地区，且已在包括中国、美国、英国、法国、德国、瑞士、澳大利亚、新加坡、泰国、阿根廷和巴西等在内的47个国家和地区获批，覆盖亚洲、欧洲、拉丁美洲、北美洲和大洋洲，是获批上市国家和地区最多的国产单抗生物类似药。近一年来，汉曲优^®在美国、泰国、菲律宾、巴西等国家和地区获批，海外版图进一步扩大，2023全年海外市场销售收入也实现了同比增长162.3%。另一方面，汉曲优^®已被纳入中国、英国、法国和德国等多个国家的医保目录，为当地患者提供更多剂型选择和灵活的组合用药方案，助力全球肿瘤诊疗高质量发展。

汉曲优^®在中国境内的销售推广由公司自建商业化团队主导，该团队以高效的执行力持续提升产品市场份额。上市四年来，凭借双规格、不含防腐剂、“即配即用”等差异化的优势，汉曲优^®获得了医生、患者以及行业等多方认可，持续引领乳腺癌治疗市场，人群覆盖不断扩大。汉曲优^®荣获了“十二五”/“十三五”国家重大新药创制专项项目支持、上海医药行业名优产品称号，入选《2022年度上海市生物医药“新优药械”产品目录》-名优产品，并获得《中国生物类似药专家共识（2020版）》、《CSCO乳腺癌诊疗指南（2023版）》、《CSCO胃癌诊疗指南（2023版）》以及《中国抗癌协会乳腺癌诊治指南与规范（2022版）》等多个权威指南和共识推荐，同时，人民日报健康客户端及健康时报第十三届健康中国年度论坛上也给予了汉曲优^®十大新药的荣誉，充分认可该产品的临床价值。此外，汉曲优^®近年来的销售额更是屡创新高，2023全年国内销售额高达人民币26.444亿元，同比增长56.1%。

复宏汉霖以国际认证的质量管理体系和强大的生产能力，为汉曲优^®的顺利出海保驾护航。2023年，汉曲优^®相关生产场地和设施接受并顺利通过美国FDA的批准前检查（Pre-license Inspection, PLI）。这是继中国和欧盟药品生产质量管理规范（GMP）认证后复宏汉霖再获国际认可，成为通过中国、欧盟、美国GMP认证的自主研发和生产抗体药物的生物制药企业。同时，公司生产基地已实现汉曲优^®对中国、欧洲、东南亚、拉美、中东等地区的商业化供货，满足全球用药需求。2024年6月，公司徐汇基地首次发货汉曲优^®至沙特阿拉伯，这也是公司首次商业化发货至中东北非地区。截至目前，汉曲优^®已在全球累计发货5,500,000+支，为全球广大HER2阳性乳腺癌和胃癌患者带来生存获益。

针对汉曲优^®，复宏汉霖致力以国际品质标准加速迈向国际化征途。从产品研发之初，复宏汉霖即开展了一系列的头对头比对研究，充分证明了汉曲优^®与原研曲妥珠单抗在质量、安全性和有效性方面高度相似，为产品的走出国门提供有力背书，其中，汉曲优^®多项质量对比研究、临床前研究及临床I期和国际多中心临床III期研究结果相继荣登BioDrugs、Cancer Chemotherapyand Pharmacology、Journal of Oncology等国际知名期刊。同时，复宏汉霖还持续发力产品的临床实践研究，多项真实世界研究先后于复旦大学肿瘤医院、南京鼓楼医院、牡丹江市肿瘤医院开展，为汉曲优^®的疗效和安全性进一步提供科学数据支持，增强全球临床用药信心，也为乳腺癌和胃癌临床研究带去更多启迪。

曲韵悠扬，四载同唱，复宏汉霖将始终秉持以患者为中心的理念，充分发挥研产销一体化的优势，将汉曲优^®等质高价优的国产生物药，带去世界更广阔的舞台，让中国制药力量真正赋能全球更多患者。

参考文献

[1] International Agency for Research on Cancer. Global Cancer Observatory: Cancer Today [DB/OL]. http://gco.iarc.who.int/today [2024-02-01]

[2] Kang S,Lee SH,Lee HJ,et al.Pathological complete response,long-term outcomes,and recurrence patterns in HER2-low versus HER2-zero breast cancer after neoadjuvant chemotherapy. Eur J Cancer.2022 Sep 29;176:30-40.

[3] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Gastric Cancer V.3.2023

Shine with differentiated advantages and demonstrated international quality

The breast cancer is the cancer with highest incidence and mortality rates among women globally. According to the data from GLOBOCAN, there were 2.3 million new cases of breast cancer worldwide in 2022 ^[1], among which, HER2-positive breast cancer accounts for approximately 20% to 25% of all breast cancer cases ^[2]. On the other hand, the reported rates of HER2 positivity in patients with gastric cancer range from 12% to 23% ^[3]. Trastuzumab has long been a cornerstone of therapy for the treatment of HER2-positive breast and gastric cancers.

HANQUYOU is the trastuzumab biosesimilar developed in accordance with the National Medical Products Administration (NMPA), the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA) and other international biosesimilar guidelines, indicated for the treatment of HER2-positive early breast cancer, metastatic breast cancer and metastatic gastric cancer. In July and August 2020, it was approved in EU and China successively. In April 2024, it received marketing approval from FDA, a significant milestone for the product, making it a China-developed mAb biosesimilar approved in China, the EU, and the U.S.

Henlius has proactively pursued overseas commercialization of HANQUYOU, collaborating with global renowned partners such as Accord, Abbott, Eurofarma and KGbio to bring its therapeutics to patients in major biopharmaceutical markets in the U.S. and Europe, as well as emerging markets, covering about 100 countries and regions. Up to date, HANQUYOU has been approved in 47 countries and regions, including China, the U.S., the UK, France, Germany, Switzerland, Australia, Singapore, Thailand, Argentina and Brazil, covering Asia, Europe, Latin America, North America, and Oceania, making it the China-developed mAb biosesimilar with the most marketing approvals. Over the past year, HANQUYOU has successfully obtained approvals in the U.S., Thailand, the Philippines, Brazil and other countries and regions, further expanding its overseas layout, and its overseas revenue from product sales for the full year of 2023 also achieved a YoY growth of 162.3%. On the other hand, it is reimbursed nationally in countries and regions including China, the UK, France and Germany, providing more dosage forms and flexible combination drug solutions for local patients and contributing to the high-quality development of global oncology diagnosis and treatment.

Henlius has established a specialized commercial team to make full efforts to develop and further tap into China market. With the advantages of dual-dosage form, no preservatives and "ready-to-use" formulation, HANQUYOU has been widely used in clinical practice and achieved rapid market acceptance and strong commercial growth. Many authoritative guidelines and regulations, such as the Chinese Consensus on Biosesimilars (2020), CSCO Guidelines for Breast Cancer (2023), CSCO Guidelines for Gastric Cancer (2023), and CACA Breast Cancer Guideline (2022), recommend HANQUYOU. It was also honored as "13th China Health Annual Forum – Top 10 New Medicine" by Health Times. In addition, HANQUYOU has achieved record sales in recent years. Its domestic sales revenue in 2023 reached approximately RMB2.6444 billion, up by 56.1% YoY. 

Benefit global patients through robust manufacturing and R&D capabilities

With its internationally certified quality management system and strong production capacity, Henlius is able to guarantee the global supply of HANQUYOU. In 2023, the manufacturing site and facility where HANQUYOU is manufactured underwent and successfully passed the Pre-License Inspection (PLI) by the FDA. The success of the FDA PLI, as well as the previous GMP certifications from China and EU regulatory agencies, make Henlius a biopharmaceutical company GMP-certificated by China, the EU and U.S. for the manufacturing of self-developed antibody drugs. Meanwhile, the company has achieved commercial supply of HANQUYOU to countries and regions including China, Europe, Southeast Asia, Latin America and the Middle East to meet the growing global market demand. In June 2024, HANQUYOU made its first delivery to Saudi Arabia, a milestone that marks company’s first commercialized delivery to the Middle East and North Africa (MENA) countries. To date, a total of 5,500,000+ units of HANQUYOU have been shipped globally, bringing survival benefits to a large number of HER2-positive breast cancer and gastric cancer patients around the world.

Henlius has benchmarked HANQUYOU against international standards in the early stages of research to enable its global commercialization. A series of head-to-head clinical studies were initiated that compared HANQUYOU with the trastuzumab originator. The clinical results demonstrated the remarkable similarity between HANQUYOU and the trastuzumab originator in terms of quality, safety, and efficacy. The results of some comparative studies, preclinical research, as well as Phase 1 and international multicenter Phase 3 clinical trials on HANQUYOU have been published on many prestigious international journals such as BioDrugs, Cancer Chemotherapy and Pharmacology, and the Journal of Oncology. In addition, Henlius has also continued its efforts in clinical research. A number of real-world studies on HANQUYOU have been conducted at esteemed medical institutions, including Fudan University Shanghai Cancer Center, The Affiliated Drum Tower Hospital of Nanjing, and Mudanjiang Tumor Hospital, which have further provided scientific data to support the efficacy and safety of HANQUYOU, boosting the confidence in its clinical practice and bringing more enlightenment to clinical research of breast cancer and gastric cancer.

After four years of dedicated effort, Henlius remains committed to patient-centricity, and will give full play to the advantages of the integration of R&D, manufacturing and commercialization, and bring domestic affordable, high-quality treatment options such as HANQUYOU to a wider stage in the world, so that Chinese pharmaceuticals will truly empower more patients around the world.