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。
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）。
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。
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。
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 biosimilar evaluated 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 biosimilar 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.
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.
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 biosimilar, 汉曲优® (trastuzumab, zercepac® in the eu), the first china-developed mab biosimilar 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.