2021-05-21
復宏漢霖利妥昔單抗類風濕關節炎 iii 期臨床研究資料在中華醫學會第二十五次全國風濕病學學術會議上發佈
2021年5月20日，複宏漢霖（2696.hk）宣佈公司自主開發的hlx01（利妥昔單抗注射液）在類風濕關節炎（rheumatoid arthritis，ra）患者中的iii期臨床試驗（hlx01-ra03，nct03522415）數據以摘要及壁報的形式於中華醫學會第二十五次全國風濕病學學術會議發佈。 這是複宏漢霖首次公佈hlx01用於ra治療的iii期臨床試驗數據，該研究的主要研究者為北京協和醫院風濕免疫科曾小峰教授。 據悉，該項臨床試驗數據亦將於近日召開的2021年歐洲風濕病學大會（eular 2021）線上平臺發佈。
hlx01（利妥昔單抗注射液）為複宏漢霖自主開發的首個單抗生物藥，同時也是中國首個根據2015年發佈的《生物類似藥研發與評價技術指導原則（試行）》開發並準予上市的生物類似藥。 hlx01已獲得中國國家藥監局準予用於非霍奇金淋巴瘤和白血病的治療，商品名為漢利康 ®， 全面覆蓋原研利妥昔單抗在中國獲批的所有適應症。 鑒於原研利妥昔單抗的類風濕關節炎適應症僅於美國和歐盟獲批，在中國尚未獲批。 複宏漢霖在開發血液腫瘤的基礎上，針對hlx01（利妥昔單抗注射液）採取了差异化的開發策略，積極探索其在類風濕關節炎患者中的療效，以期惠及更多患者群體。 2020年12月，hlx01（利妥昔單抗注射液）用於ra治療的上市註冊申請（nda）獲得國家藥品監督管理局（nmpa）正式受理。
hlx01-ra03數據發佈詳情：
● 論文題目
efficacy and safety of hlx01 in patients with moderately to severely active rheumatoid arthritis who had inadequate responses to methotrexate: results of a randomised, double-blind, placebo-controlled phase 3 study
● 主要研究者
曾小峰，北京協和醫院
● 展示形式
摘要及壁報
● 摘要編號
2099
● 試驗設計
hlx01-ra03是一項在甲氨蝶呤治療應答不完全（mtx-ir）的中重度活動性類風濕關節炎患者中評估hlx01（利妥昔單抗注射液）聯合甲氨蝶呤（mtx）治療的有效性和安全性的隨機、雙盲、安慰劑對照的iii期臨床研究。 納入的患者按2:1隨機分為兩組，分別在第1天和第15天靜脈輸注1000 mg hlx01或安慰劑。 在第169天（第24周第1天）和第183天，hlx01組和安慰劑組受試者均靜脈輸注1000 mg hlx01。 同時，所有受試者均接收穩定劑量的甲氨蝶呤（mtx）。 第16周和20周時如患者對已接受治療無應答，則進行挽救治療。 該研究的主要終點為第24周達到美國風濕病學會20%緩解標準（acr20）的患者比例。
● 試驗結果
1）有效性
a）主要終點
本試驗共入組275名患者（hlx01組，n = 183；安慰劑組，n = 92）。 24周時，意向分析集（itt）人群中hlx01組達到acr20的患者比例相較於安慰劑組有顯著的提升（60.7% vs 35.9%；odds ratio [or]，2.756 [95% ci 1.640，4.632]；p <；0.001）。
b）次要終點
次要療效終點包含達到acr20/50/70反應標準的患者比例、基於c反應蛋白（crp）及基於血沉（esr）的28關節疾病活動度評分（das28）、基於健康評估問卷殘疾指數（haq-di）評估軀體功能的改善等。 試驗結果顯示，hlx01各次要療效終點較安慰劑也有顯著的提升。
2）安全性
實驗組和安慰劑對照組治療後不良事件（teae）、藥物不良反應（adr）及導致研究藥物停用的teae的發生率均相似。
● 結論
hlx01聯合甲氨蝶呤相較於安慰劑，在甲氨蝶呤治療應答不完全的中國中重度活動性類風濕關節炎受試者中具有顯著的臨床療效和良好的安全性，證明hlx01聯合mtx是一種可耐受、安全、有效的治療選擇。
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開展20多項臨床試驗，產品對外授權覆蓋全球近100個國家和地區。
phase 3 clinical results of rituximab injection hlx01 in ra patients was first released by henlius at the 25th
national congress of chinese rheumatology association
shanghai, china, 20th may, 2021 - shanghai henlius biotech, inc. (2696.hk) announced that the abstract and poster of phase 3 clinical trial (hlx01-ra03，nct03522415) results of hlx01, a rituximab injection which was independently developed by henlius for the treatment of rheumatoid arthritis was reported at the 25th national congress of chinese rheumatology association by the company. this is the first time for henlius to release the results of hlx01-ra03. professor xiaofeng zeng from department of rheumatology and immunology, peking union medical college hospital is the leading principal investigator of this study. this clinical trial data will also be released on the online platform of european congress of rheumatology 2021(eular 2021) in the coming days.
hlx01 ( rituximab injection) is the first monoclonal antibody (mab) biosimilar independently developed by henlius and the first-ever china-manufactured biosimilar approved by the nmpa in accordance with the technical guidelines for the development and evaluation of biosimilars (tentative). it has been approved for the treatment of non-hodgkin's lymphoma and leukemia, covering all the indications approved for the rituximab originator in chinese mainland. since the rituximab originator has not been approved for ra in china, henlius has adopted a differentiated strategy to fully develop the potential of hlx01 (rituximab injection) in ra and to benefit a broader patient population. in december 2020, the national medical products administration (nmpa) has accepted the new drug application (nda) for a new indication of hlx01 to treat ra.
details of the publications of hlx01-ra03:
● title
efficacy and safety of hlx01 in patients with moderately to severely active rheumatoid arthritis who had inadequate responses to methotrexate: results of a randomised, double-blind, placebo-controlled phase 3 study
● leading pi
xiaofeng zeng, md, phd, peking union medical college hospital
● form
abstract and poster
● abstract no.
2099
● study design
hlx01-ra03 is a randomised, double-blind, placebo-controlled, phase 3 study aimed to evaluate the efficacy and safety of hlx01 (rituximab injection) in combination with methotrexate (mtx) in patients with moderate to severe active rheumatoid arthritis (ra) who have had mtx-inadequate response (mtx-ir). eligible patients were randomised 2:1 to receive 1000 mg hlx01 or placebo on day 1 and day 15 by intravenous infusion. patients were retreated with or switched to receive (if initially assigned to placebo) 1000 mg hlx01 on day 169 (the first day of week 24) and day 183. a stable dose of mtx was administered to all patients during the study. patients with inadequate responses at week 16 and week 20 could receive rescue treatments. the primary endpoint of the study is the proportion of patients who met american college of rheumatology 20 (acr20) criteria at week 24.
● results
1) efficacy
a) primary endpoint
275 patients were enrolled (hlx01 group, n = 183; placebo group, n = 92) in this study. a significantly greater proportion of patients achieved acr20 response in the hlx01 group compared with the placebo group in the itt population at week 24 (60.7% vs 35.9%; odds ratio [or], 2.756 [95% ci 1.640, 4.632]; p < 0.001).
b) secondary endpoints
the secondary efficacy endpoints include proportions of patients achieving acr20/50/70, disease activity score measured by 28 joints (das28) based on c-reactive protein (crp) and erythrocyte sedimentation rate (esr), improvement in physical function assessed by health assessment questionnaire-disability index (haq-di), and so on. the results demonstrated that the secondary efficacy endpoints were also significantly improved in hlx01 group compared with placebo group.
2) safety
the overall incidence of treatment emergent adverse events (teaes), adverse drug reactions (adrs), and teaes leading to drug discontinuation were similar among treatment groups.
● conclusion
hlx01 plus mtx showed significantly improved clinical outcomes and comparable safety profiles compared with placebo in chinese patients with moderate to severe active ra who had inadequate responses to mtx, demonstrating hlx01 in combination with mtx as a well-tolerated, safe, and efficient treatment option.
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 (ndas) 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 innovative product serplulimab indicated for msi-h solid tumors has been granted priority review, and the ndas of hlx04 (bevacizumab) and hlx01 (rituximab) for the treatment of rheumatoid arthritis are also 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.