復宏漢霖達雷妥尤單抗類似藥正式獲批臨床
2021年1月13日，復宏漢霖（香港聯交所代碼：2696.HK）今日宣布，國家藥品監督管理局（NMPA）正式批準了公司自主開發的達雷妥尤單抗生物類似藥HLX15（重組抗CD38全人單克隆抗體注射液）的臨床試驗申請，用于多發性骨髓瘤（MM）的治療。
HLX15是復宏漢霖自主開發的一款全人源抗CD38 IgG1κ單克隆抗體。一方面，HLX15可直接與腫瘤細胞表面表達的CD38結合，通過補體依賴的細胞毒作用（CDC）、抗體依賴的細胞毒作用（ADCC）、抗體依賴的細胞吞噬作用（ADCP）、以及Fc介導的交聯作用等多重反應誘導骨髓瘤細胞凋亡和溶解，達到快速緩解；此外，HLX15還可通過降低髓源性抑制細胞和消耗CD38表達陽性的免疫調節性T、B細胞來調節免疫微環境，增強免疫系統對腫瘤細胞的抑制作用。參照NMPA發布的《生物類似藥研發與評價技術指導原則（試行）》和EMA發布的Guideline on Similar Biological Medicinal Products的要求，復宏漢霖采用逐步遞進、比對及相似性評價原則，對HLX15與原研達雷妥尤單抗進行了頭對頭的藥學分析和體內外藥理學比對研究。研究結果顯示，HLX15和原研達雷妥尤單抗具有高度相似性。
多發性骨髓瘤是血液系統中第二大類常見惡性腫瘤，約占血液系統惡性腫瘤的10% [1] 。研究發現，CD38在大量惡性血液癌癥特別是多發性骨髓瘤等癌癥中高度表達，被認為是多發性骨髓瘤治療性抗體藥物的理想開發靶點-1。達雷妥尤單抗是全球首個獲批上市的靶向作用于CD38的單克隆抗體，目前該藥已在中國獲批單藥治療復發和難治性多發性骨髓瘤成年患者，其多種聯合療法亦已在全球獲批用于多發性骨髓瘤患者的一線、二線及以上治療。根據IQVIA數據統計，2019年度達雷妥尤單抗于全球范圍內的銷售額超過28億美元，市場需求巨大。
2019年，復宏漢霖成功推出中國首個生物類似藥漢利康®，用于非霍奇金淋巴瘤和慢性淋巴細胞白血病的治療。至此，HLX15成為復宏漢霖又一款自主開發的血液腫瘤治療產品，進一步拓展了復宏漢霖豐富的產品管線。同時， HLX15的開發有望緩解患者的經濟負擔，為國內多發性骨髓瘤患者，尤其是復發和難治性患者帶來優質的治療新選擇。在持續推進生物類似藥產品開發的同時，復宏漢霖也將不斷拓展公司創新產品管線，憑借已經建立起的完善的創新研發平臺，持續高效地為全球患者提供可負擔的、療效更好的治療方案。
關于復宏漢霖
復宏漢霖（2696.HK）是一家國際化的創新生物制藥公司，致力于為全球患者提供質高價優的創新生物藥，產品覆蓋腫瘤、自身免疫疾病、眼科疾病等領域。自2010年成立以來，復宏漢霖已建成一體化生物制藥平臺，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。公司在全球已建立完善的研發中心，按照國際GMP標準進行生產和質量管控，位于上海徐匯的生產基地已獲得中國和歐盟GMP認證。
復宏漢霖前瞻性布局了一個多元化、高質量的產品管線，涵蓋20多種創新單克隆抗體，并全面推進基于自有抗PD-1單抗HLX10的腫瘤免疫聯合療法。截至目前，公司已成功上市3個單抗生物藥，包括國內首個生物類似藥漢利康®（利妥昔單抗）、首個中歐雙批的國產生物類似藥漢曲優®（曲妥珠單抗，歐盟商品名：Zercepac®）以及公司首個自身免疫疾病治療產品漢達遠®（阿達木單抗）。此外，HLX04貝伐珠單抗及HLX01利妥昔單抗類風濕關節炎新適應癥的上市注冊申請正在審評中，公司亦同步就10個產品、8個聯合治療方案于全球范圍內開展20多項臨床試驗，產品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。
Henlius Daratumumab Biosimilar Received IND Approval from NMPA
Shanghai, China, Jan, 13th, 2021 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the Investigational New Drug (IND) application of ?the Company's daratumumab biosimilar HLX15, a recombinant anti-CD38 fully human monoclonal antibody injection, for the treatment of multiple myeloma (MM) has been approved by the National Medical Products Administration (NMPA).?
HLX15 is a fully human anti-CD38 IgG1κ monoclonal antibody independently developed by Henlius. On one hand, HLX15 can directly bind to CD38 expressed on the surface of tumor cells, inducing tumor cell lysis and apoptosis through complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), and several other pathways such as Fc mediated cross linking to achieve a quick response of tumor cells. In addition, HLX15 can also reduce multiple myeloma cells by reducing myeloid-derived suppressor cells and depleting CD38-positive immunomodulatory T and B cells. In accordance with the Technical Guidelines of Development and Evaluation of Biosimilar Drugs and EMA Guideline on Similar Biological Medicinal Products, HLX15 has been developed strictly following the principles of stepwise development, comparability and similarity assessment and has been compared head to head with reference daratumumab via analytical studies and preclinical studies. The results of these studies showed that HLX15 is highly similar to reference daratumumab.
Multiple Myeloma is the second most common hematologic malignancies and accounts for approximately 10% of hematologic malignant cases[1] ?. High expression of CD38 is present in varied of hematologic malignancies and all stages along disease progression of multiple myeloma. Considering the expression profile of CD38, it is thought to be an ideal target for the treatment of multiple myeloma-1. Daratumumab is the first CD38-directed monoclonal antibody approved globally and has been approved for the single-agent treatment of adult patients with recurrent and refractory multiple myeloma by NMPA. Its combinations have also been approved for the treatment of first-line, second-line and above multiple myeloma patients globally. According to estimates from IQVIA, total sales of daratumumab worldwide has reached USD 2.8 billion, indicating a huge medical needs for this drug.
In 2019，Henlius has launched the first domestic monoclonal antibody biosimilar 漢利康® to treat non-Hodgkin's lymphoma and chronic lymphocytic lleukemia. HLX15 is the second product in the area of hematologic malignancies developed by Henlius, further extending the Company’s enriched portfolio. Meanwhile, HLX15 has the potential to reduce the financial burden of patients with multiple myeloma and provide them an alternative high-quality treatment option, especially for recurrent and refractory patients. Looking forward, Henlius will continue expanding the well-established biosimilar products pipeline and promoting the development of innovative biologics. On the basis of its established and integrated innovation platform, the Company will underscore its long-term commitment to providing affordable and effective therapies for patients worldwide.
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. 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 European Union (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 HLX10 (anti-PD-1 mAb) as backbone. Up to date, Henlius has launched three mAbs developed independently: 漢利康® (HLX01, rituximab), the first China-developed biosimilar, 漢曲優® (HLX02, trastuzumab, Zercepac® in the EU), the first China-developed mAb biosimilar approved both in China and in the EU and 漢達遠® (HLX03, adalimumab), the Company's first product indicated for autoimmune diseases. In addition, the New Drug Applications of HLX04 (bevacizumab) and HLX01 (rituximab) for the treatment of rheumatoid arthritis are under review, and 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.
參考文獻
[1] Rajkumar SV, Kumar S. Multiple Myeloma: Diagnosis and Treatment [J]. Mayo Clinic Proceedings, 2016, 91(1):101-119.
[2] Bonello, F., M. D'Agostino, M. Moscvin, C. Cerrato, M. Boccadoro, and F. Gay. 2018. 'CD38 as an immunotherapeutic target in multiple myeloma', Expert Opin Biol Ther, 18: 1209-21.
[3] Morandi, F., A. L. Horenstein, F. Costa, N. Giuliani, V. Pistoia, and F. Malavasi. 2018. 'CD38: A Target for Immunotherapeutic Approaches in Multiple Myeloma', Front Immunol, 9: 2722.