BioDrugs 發表復宏漢霖漢曲優®國際多中心 III 期臨床研究結果
近日，由中國醫學科學院腫瘤醫院國家新藥（抗腫瘤）臨床研究中心主任徐兵河教授牽頭開展的漢曲優 ® （曲妥珠單抗，歐盟商品名：Zercepac ®） 國際多中心III期臨床試驗HLX02-BC01（臨床試驗號：NCT03084237；歐洲臨床試驗號：2016-000206-10）研究結果在生物藥領域老牌權威雜誌Biodrugs上成功發表。 此前，漢曲優 ® 的質量對比研究和I期臨床試驗（HLX02-HV01，NCT02581748）研究結果曾分別刊登於Biodrugs和腫瘤治療領域知名雜誌Cancer Chemotherapy and Pharmacology。
首個經國際多中心III期臨床試驗評估的國產生物類似藥
HLX02-BC01是一項在中國、菲律賓、波蘭、烏克蘭等89個中心同步開展的隨機、雙盲、國際多中心的III期臨床研究，旨在評估漢曲優 ® 和原研曲妥珠單抗在未經系統治療的HER2陽性復發及轉移性乳腺癌患者中的療效、安全性和免疫原性。 該研究共計入組了649例受試者，為國內HER2陽性乳腺癌中樣本量最大的生物類似藥臨床研究。 受試者按照1:1的比例隨機分為兩組，分別靜脈注射給予漢曲優 ® 聯合多西他賽或歐洲市售曲妥珠單抗聯合多西他賽（初始劑量為8 mg/kg，隨後每三周注射6 mg/kg藥品至12個月）。 研究的主要終點為24周的總緩解率（ORR24w）。
此前，該項研究結果曾多次在國際學術會議上進行發表和彙報。 複宏漢霖於2019年CSCO大會上首次發佈了HLX02-BC01的亞組分析結果，並於2019年ESMO大會及ESMO Asia大會上報告了該試驗用藥24周的有效性、安全性數據。 2020年ESMO大會上，公司進一步分享了該研究隨訪1年的有效性、安全性數據和群體藥代動力學數據。 此外，該研究的臨床獲益率（CBR）、疾病控制率（DCR）、緩解持續時間（DoR）和無進展生存期（PFS）等研究數據也於2020年第十二届歐洲乳腺癌大會（EBCC）上公佈。
漢曲優 ® 組（n = 324）和歐洲市售曲妥珠單抗組（n = 325）的ORR24w分別為71.3%和71.4%。 組間差异為−0.1%（95%置信區間：−7%，6.9%），完全落在預設的等效範圍內（±13.5%）。 且所有的次要療效分析均無顯著的統計學差异。 漢曲優 ® 和歐洲市售曲妥珠單抗的安全性和免疫原性結果相似。 研究結果充分證明漢曲優 ® 與原研曲妥珠單抗在招募的全球各地區的HER2陽性復發或轉移性乳腺癌患者中具有相似的療效和安全性。
國際品質開啟中國生物醫藥國際化新篇章
HLX02-BC01的臨床結果進一步證實了漢曲優 ® 與原研曲妥珠單抗的相似性，有效支持了漢曲優 ® 作為HER2陽性乳腺癌領域可負擔的、高品質的治療新選擇的臨床應用。 基於漢曲優 ® 的質量對比研究、臨床前研究及HLX02-HV01、HLX02-BC01的關鍵臨床研究結果，2019年複宏漢霖同步向中國國家藥品監督管理局（NMPA）和歐洲藥品管理局（EMA）遞交了漢曲優 ® 的上市申請。 2020年7月及8月，漢曲優 ® 先後在歐盟和中國獲得批准上市，用於HER2陽性乳腺癌和胃癌的治療，成為中國首個自主研發的中歐雙批單抗藥物，以對標國際標準的質量開啟了中國生物醫藥研發成果的國際化新篇章。 現時，漢曲優 ® 已在包括德國、西班牙、法國、愛爾蘭、義大利、匈牙利等近20個歐盟國家和地區成功上市，並在英國進入國家醫保和全球多家頂級醫院，包括倫敦的Chelsea Hospital、Westminster and Kings College Hospital等。
同時，漢曲優 ® 的獲批上市也對國內HER2治療的臨床實踐產生了積極影響，進一步解决了患者和臨床醫生未滿足的用藥需求，提升了我國單抗生物藥的可及性。 截至目前，漢曲優 ® 已開通全國所有省市的醫保准入，於28個省市完成招標掛網，為惠及更多患者打下了堅實基礎。 複宏漢霖亦計畫進一步擴充漢曲優 ® 的銷售隊伍並加强銷售網路計畫，並著力夯實HER2陽性患者診療生態圈建設，積極與相關企業展開合作，加快推進產品的市場下沉，“不讓一個HER2陽性患者落下”。
關於Biodrugs
Biodrugs為生物藥領域老牌權威期刊，主要圍繞基於生物技術的藥物和診斷產品的開發和應用，覆蓋生物醫學、藥學、生物技術、腫瘤與血液學、金融、商業和銀行業等領域，是生物療法領域科學家、專業研發人員和臨床醫生的重要參攷資源。
關於複宏漢霖
複宏漢霖（2696.HK）是一家國際化的創新生物製藥公司，致力於為全球患者提供可負擔的高品質生物藥，產品覆蓋腫瘤、自身免疫疾病、眼科疾病等領域，已在中國上市3款產品，在歐盟上市1款產品，3款產品獲得中國上市註冊申請受理。 自2010年成立以來，複宏漢霖已建成一體化生物製藥平臺，高效及創新的自主核心能力貫穿研發、生產及商業運營全產業鏈。 公司已建立完善高效的全球研發中心，按照國際GMP標準進行生產和質量管控，位於上海徐匯的生產基地已獲得中國和歐盟GMP認證。
複宏漢霖前瞻性佈局了一個多元化、高品質的產品管線，涵蓋20多種創新單克隆抗躰，並全面推進基於自有抗PD-1單抗斯魯利單抗的腫瘤免疫聯合療法。 繼國內首個生物類似藥漢利康 ® （利妥昔單抗）、中國首個自主研發的中歐雙批單抗藥物漢曲優 ® （曲妥珠單抗，歐盟商品名：Zercepac ®）、 公司首個自身免疫疾病治療產品漢達遠 ® （阿達木單抗）相繼獲批上市，創新產品斯魯利單抗MSI-H實體瘤的上市註冊申請已納入優先審評審批程式，HLX04貝伐珠單抗及HLX01利妥昔單抗類風濕關節炎新適應症的上市註冊申請也正在審評中。 公司亦同步就10個產品、8個聯合治療方案在全球範圍內開展20多項臨床試驗，對外授權全面覆蓋歐美主流生物藥市場和眾多新興國家市場。
Biodrugs Published the Results of the International Multicentre Phase 3 Clinical Trial of 漢曲優 ®
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：https://link.springer.com/article/10.1007/s40259-021-00475-w