复宏汉霖达雷妥尤单抗类似药正式获批临床
2021年1月13日，复宏汉霖（香港联交所代码：2696.HK）今日宣布，国家药品监督管理局（NMPA）正式批准了公司自主开发的达雷妥尤单抗生物类似药HLX15（重组抗CD38全人单克隆抗体注射液）的临床试验申请，用于多发性骨髓瘤（MM）的治疗。
HLX15是复宏汉霖自主开发的一款全人源抗CD38 IgG1κ单克隆抗体。一方面，HLX15可直接与肿瘤细胞表面表达的CD38结合，通过补体依赖的细胞毒作用（CDC）、抗体依赖的细胞毒作用（ADCC）、抗体依赖的细胞吞噬作用（ADCP）、以及Fc介导的交联作用等多重反应诱导骨髓瘤细胞凋亡和溶解，达到快速缓解；此外，HLX15还可通过降低髓源性抑制细胞和消耗CD38表达阳性的免疫调节性T、B细胞来调节免疫微环境，增强免疫系统对肿瘤细胞的抑制作用。参照NMPA发布的《生物类似药研发与评价技术指导原则（试行）》和EMA发布的Guideline on Similar Biological Medicinal Products的要求，复宏汉霖采用逐步递进、比对及相似性评价原则，对HLX15与原研达雷妥尤单抗进行了头对头的药学分析和体内外药理学比对研究。研究结果显示，HLX15和原研达雷妥尤单抗具有高度相似性。
多发性骨髓瘤是血液系统中第二大类常见恶性肿瘤，约占血液系统恶性肿瘤的10% [1] 。研究发现，CD38在大量恶性血液癌症特别是多发性骨髓瘤等癌症中高度表达，被认为是多发性骨髓瘤治疗性抗体药物的理想开发靶点-1。达雷妥尤单抗是全球首个获批上市的靶向作用于CD38的单克隆抗体，目前该药已在中国获批单药治疗复发和难治性多发性骨髓瘤成年患者，其多种联合疗法亦已在全球获批用于多发性骨髓瘤患者的一线、二线及以上治疗。根据IQVIA数据统计，2019年度达雷妥尤单抗于全球范围内的销售额超过28亿美元，市场需求巨大。
2019年，复宏汉霖成功推出中国首个生物类似药汉利康®，用于非霍奇金淋巴瘤和慢性淋巴细胞白血病的治疗。至此，HLX15成为复宏汉霖又一款自主开发的血液肿瘤治疗产品，进一步拓展了复宏汉霖丰富的产品管线。同时， HLX15的开发有望缓解患者的经济负担，为国内多发性骨髓瘤患者，尤其是复发和难治性患者带来优质的治疗新选择。在持续推进生物类似药产品开发的同时，复宏汉霖也将不断拓展公司创新产品管线，凭借已经建立起的完善的创新研发平台，持续高效地为全球患者提供可负担的、疗效更好的治疗方案。
关于复宏汉霖
复宏汉霖（2696.HK）是一家国际化的创新生物制药公司，致力于为全球患者提供质高价优的创新生物药，产品覆盖肿瘤、自身免疫疾病、眼科疾病等领域。自2010年成立以来，复宏汉霖已建成一体化生物制药平台，高效及创新的自主核心能力贯穿研发、生产及商业运营全产业链。公司在全球已建立完善的研发中心，按照国际GMP标准进行生产和质量管控，位于上海徐汇的生产基地已获得中国和欧盟GMP认证。
复宏汉霖前瞻性布局了一个多元化、高质量的产品管线，涵盖20多种创新单克隆抗体，并全面推进基于自有抗PD-1单抗HLX10的肿瘤免疫联合疗法。截至目前，公司已成功上市3个单抗生物药，包括国内首个生物类似药汉利康®（利妥昔单抗）、首个中欧双批的国产生物类似药汉曲优®（曲妥珠单抗，欧盟商品名：Zercepac®）以及公司首个自身免疫疾病治疗产品汉达远®（阿达木单抗）。此外，HLX04贝伐珠单抗及HLX01利妥昔单抗类风湿关节炎新适应症的上市注册申请正在审评中，公司亦同步就10个产品、8个联合治疗方案于全球范围内开展20多项临床试验，产品对外授权全面覆盖欧美主流生物药市场和众多新兴国家市场。
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 汉利康® 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: 汉利康® (HLX01, rituximab), the first China-developed biosimilar, 汉曲优® (HLX02, trastuzumab, Zercepac® in the EU), the first China-developed mAb biosimilar approved both in China and in the EU and 汉达远® (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.
参考文献
[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.