Recently, Biodrugs published the results of the global multicentre Phase 3 clinical trial (HLX02-BC01, NCT03084237 and EudraCT: 2016-000206-10) of 漢曲優 ^®, (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 漢曲優 ^® 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 漢曲優 ^® 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 漢曲優 ^® 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 漢曲優 ^®and the EU-trastuzumab. The results of the phase 3 study demonstrated that 漢曲優 ^® 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 漢曲優 ^® and reference trastuzumab and supported the clinical application of 漢曲優 ^® 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漢曲優 ^® 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漢曲優 ^® 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 漢曲優 ^® 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, 漢曲優 ^® 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 漢曲優 ^®, 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 漢利康 ^®(rituximab), the first China-developed biosimilar, 漢曲優 ^® (trastuzumab, Zercepac^® in the EU), the first China-developed mAb biosimilar approved both in China and in the EU and漢達遠 ^®(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.

原文連結：//link.springer.com/article/10.1007/s40259-021-00475-w