BioDrugs 发表复宏汉霖汉曲优®国际多中心 III 期临床研究结果
近日，由中国医学科学院肿瘤医院国家新药（抗肿瘤）临床研究中心主任徐兵河教授牵头开展的汉曲优®（曲妥珠单抗，欧盟商品名：Zercepac®）国际多中心III期临床试验HLX02-BC01（临床试验号：NCT03084237；欧洲临床试验号：2016-000206-10）研究结果在生物药领域老牌权威杂志Biodrugs上成功发表。此前，汉曲优®的质量对比研究和I期临床试验（HLX02-HV01，NCT02581748）研究结果曾分别刊登于Biodrugs和肿瘤治疗领域知名杂志Cancer Chemotherapy and Pharmacology。
首个经国际多中心III期临床试验评估的国产生物类似药
HLX02-BC01是一项在中国、菲律宾、波兰、乌克兰等89个中心同步开展的随机、双盲、国际多中心的III期临床研究，旨在评估汉曲优®和原研曲妥珠单抗在未经系统治疗的HER2阳性复发及转移性乳腺癌患者中的疗效、安全性和免疫原性。该研究共计入组了649例受试者，为国内HER2阳性乳腺癌中样本量最大的生物类似药临床研究。受试者按照1:1的比例随机分为两组，分别静脉注射给予汉曲优®联合多西他赛或欧洲市售曲妥珠单抗联合多西他赛（初始剂量为8 mg/kg，随后每三周注射6 mg/kg药品至12个月）。研究的主要终点为24周的总缓解率（ORR24w）。
此前，该项研究结果曾多次在国际学术会议上进行发表和汇报。复宏汉霖于2019年CSCO大会上首次发布了HLX02-BC01的亚组分析结果，并于2019年ESMO大会及ESMO Asia大会上报告了该试验用药24周的有效性、安全性数据。2020年ESMO大会上，公司进一步分享了该研究随访1年的有效性、安全性数据和群体药代动力学数据。此外，该研究的临床获益率（CBR）、疾病控制率（DCR）、缓解持续时间（DoR）和无进展生存期（PFS）等研究数据也于2020年第十二届欧洲乳腺癌大会（EBCC）上公布。
汉曲优®组（n = 324）和欧洲市售曲妥珠单抗组（n = 325）的ORR24w分别为71.3%和71.4%。组间差异为−0.1%（95%置信区间：−7%, 6.9%），完全落在预设的等效范围内（±13.5%）。且所有的次要疗效分析均无显著的统计学差异。汉曲优®和欧洲市售曲妥珠单抗的安全性和免疫原性结果相似。研究结果充分证明汉曲优®与原研曲妥珠单抗在招募的全球各地区的HER2阳性复发或转移性乳腺癌患者中具有相似的疗效和安全性。
国际品质开启中国生物医药国际化新篇章
HLX02-BC01的临床结果进一步证实了汉曲优®与原研曲妥珠单抗的相似性，有效支持了汉曲优®作为HER2阳性乳腺癌领域可负担的、高品质的治疗新选择的临床应用。基于汉曲优®的质量对比研究、临床前研究及HLX02-HV01、HLX02-BC01的关键临床研究结果，2019年复宏汉霖同步向中国国家药品监督管理局（NMPA）和欧洲药品管理局（EMA）递交了汉曲优®的上市申请。2020年7月及8月，汉曲优®先后在欧盟和中国获得批准上市，用于HER2阳性乳腺癌和胃癌的治疗，成为中国首个自主研发的中欧双批单抗药物，以对标国际标准的质量开启了中国生物医药研发成果的国际化新篇章。目前，汉曲优®已在包括德国、西班牙、法国、爱尔兰、意大利、匈牙利等近20个欧盟国家和地区成功上市，并在英国进入国家医保和全球多家顶级医院，包括伦敦的Chelsea Hospital、Westminster and Kings College Hospital等。
同时，汉曲优®的获批上市也对国内HER2治疗的临床实践产生了积极影响，进一步解决了患者和临床医生未满足的用药需求，提升了我国单抗生物药的可及性。截至目前，汉曲优®已开通全国所有省市的医保准入，于28个省市完成招标挂网，为惠及更多患者打下了坚实基础。复宏汉霖亦计划进一步扩充汉曲优®的销售队伍并加强销售网络计划，并着力夯实HER2阳性患者诊疗生态圈建设，积极与相关企业展开合作，加快推进产品的市场下沉，“不让一个HER2阳性患者落下”。
关于Biodrugs
Biodrugs为生物药领域老牌权威期刊，主要围绕基于生物技术的药物和诊断产品的开发和应用，覆盖生物医学、药学、生物技术、肿瘤与血液学、金融、商业和银行业等领域，是生物疗法领域科学家、专业研发人员和临床医生的重要参考资源。
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3款产品，在欧盟上市1款产品，3款产品获得中国上市注册申请受理。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单抗斯鲁利单抗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，欧盟商品名：Zercepac®）、公司首个自身免疫疾病治疗产品汉达远®（阿达木单抗）相继获批上市，创新产品斯鲁利单抗MSI-H实体瘤的上市注册申请已纳入优先审评审批程序，HLX04贝伐珠单抗及HLX01利妥昔单抗类风湿关节炎新适应症的上市注册申请也正在审评中。公司亦同步就10个产品、8个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国家市场。
Biodrugs Published the Results of the International Multicentre Phase 3 Clinical Trial of 汉曲优®
Recently, Biodrugs published the results of the global multicentre Phase 3 clinical trial (HLX02-BC01, NCT03084237 and EudraCT: 2016-000206-10) of 汉曲优®, (trastuzumab, EU brand name: Zercepac®) which was led by Professor Binghe Xu, the director of the National New Drug Clinical Research Centre of Cancer Hospital Chinese Academy of Medical Sciences. Previously, the analytical and preclinical study and Phase 1 clinical study (HLX02-HV01, NCT02581748) results of 汉曲优® were published on Biodrugs and Cancer Chemotherapy and Pharmacology, a well-known oncology journal, respectively.
The First China-manufactured Biosesimilar evalsuated in an International Multicentre Phase 3 Clinical Study
HLX02-BC01, a randomised, double-blind, international Phase 3 clinical study conducted at 89 centres in China, the Philippines, Poland, and Ukraine, was aimed to compare the efficacy, safety, and immunogenicity of 汉曲优® with reference trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive recurrent or metastatic breast cancer who had not received prior systemic treatment. In total, 649 patients were enrolled in this study, ranking it as the largest clinical trial conducted among HER2-positive patients in China. Eligible patients were randomised 1:1 to receive either 汉曲优® or European Union (EU)-sourced trastuzumab (initial dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks for up to 12 months) in combination with docetaxel intravenously. The primary endpoint was overall response rate up to week 24 (ORR24w).
The results of HLX02-BC01 were presented multiple times at different international academic congresses. The subgroup analysis results of HLX02-BC01 were released for the first time at the 2019 CSCO (Chinese Society of Clinical Oncology) Congress. The efficacy and safety results up to week 24 were presented at the 2019 ESMO (European Society for Medical Oncology) and ESMO-Asia Congress. The 1-year efficacy and safety results of HLX02-BC01 and the PopPK model were reported at the 2020 ESMO Congress. In addition, the clinical benefit rate (CBR), disease control rate (DCR), duration of response (DoR) and progression-free survival (PFS) results of this study were published at the 12th EBCC (European Breast Cancer Conference) in 2020.
The ORR24w were 71.3% in the 汉曲优® group (n = 324) and 71.4% in the EU-trastuzumab group (n = 325). The group difference was −0.1% (95% confidence interval: −7%, 6.9%), which fell entirely in the predefined equivalence margins (±13.5%). No statistically significant differences were observed in all secondary efficacy analyses. Safety profiles and immunogenicity were similar between 汉曲优® and the EU-trastuzumab. The results of the phase 3 study demonstrated that 汉曲优® and reference trastuzumab had equivalent efficacy and similar safety results in HER2-positive recurrent or metastatic breast cancer patients who were recruited from different regions of the world.
Accordance with International Quality Standards Opens up Global Era of Chinese Biologic Medicine
The reliable study results of HLX02-BC01 further demonstrated the similarity between 汉曲优® and reference trastuzumab and supported the clinical application of 汉曲优® as an affordable, high-quality new option in the treatment of HER2-positive breast cancer. On the basis of its analytical studies, preclinical studies, the Phase 1 clinical study and the pivotal global multicentre Phase 3 clinical study, Henlius submitted the new drug application(NDA) and marketing authorization application(MAA) of汉曲优® to NMPA and EMA and had been approved for the treatment of HER2 positive breast cancer and gastric cancer in the European Union(EU) and China respectively in July and August 2020, making汉曲优® the first China-developed mAb biosesimilar to be approved both in China and in the EU, and opening up the international development new era of Chinese biologic medicine. As of now, Zercepac® (150mg) had successfully entered a number of top hospitals in the UK (including Chelsea Hospital, Westminster and Kings College Hospital in London, etc.). In addition to the UK, Zercepac® (150mg) has been successfully marketed in nearly 20 EU countries and regions including Germany, Spain, France, Italy, Ireland, and Hungary.
Meanwhile, the approval of 汉曲优® has also had a positive impact on clinical landscape of HER2 treatment in China, further addressing the unmet medical needs of patients and doctors and improving the accessibility of mAb biologics in China. As of now, 汉曲优® has completed all the provincial medical insurance access work and tendering process in 28 provinces and municipalities, laying a strong foundation to benefit more patients. Looking forward, Henlius will further expand the sales team and enhance the sales network of 汉曲优®, make full efforts to consolidate the diagnosis and treatment ecosystem for HER2-positive patients and actively cooperate with business partners to accelerate the penetration in domestic market of the product, not leaving any HER2 cancer patient behind.
About Biodrugs
As an essential resource for R&D professionals and clinicians with an interest in biologic therapies, BioDrugs covers the development and therapeutic application of biotechnology-based pharmaceuticals and diagnostic products for the treatment of human disease.
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, 3 products have been launched in China, 1 in the European Union (EU), the New Drug Applications (NDA) of 3 products 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 commercialisation. It has established global R&D 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 serplulimab (anti-PD-1 mAb) as backbone. Apart from the launched products 汉利康® (rituximab), the first China-developed biosesimilar, 汉曲优® (trastuzumab, Zercepac® in the EU), the first China-developed mAb biosesimilar approved both in China and in the EU and 汉达远® (adalimumab), the Company's first product indicated for autoimmune diseases, the NDA of HLX04 (bevacizumab) and the two innovative mAbs HLX01 (rituximab) for the treatment of rheumatoid arthritis and serplulimab indicated for MSI-H solid tumors are under review. What's more, Henlius has conducted over 20 clinical studies for 10 products and 8 combination therapies worldwide, expanding its presence in major market as well as emerging market.
原文链接：https://link.springer.com/article/10.1007/s40259-021-00475-w