第三个境外临床允许，复宏汉霖贝伐珠单抗HLX04-O眼科顺应症于欧盟获批临床
2020年10月，复宏汉霖与亿胜生物告竣相助配合开发HLX04-O，双方妄想围绕HLX04-O眼科顺应症在中国、澳大利亚、欧盟、美国等国家和地区开展国际多中央临床试验，并依附研究效果在全球多个国家和地区同步举行上市申报 。复宏汉霖已开展了HLX04-O玻璃体注射治疗wAMD的非临床药效学、清静药理学、重复给药毒性、药代动力学、毒代动力学、免疫毒性、免疫原性、局部刺激性试验等相关研究，起源证实晰HLX04-O玻璃体注射有用和清静 。一项全球、多中央的III期临床研究拟于近期在中国、澳大利亚、俄罗斯联邦、新加坡、西班牙、波兰等国家和地区开展，以进一步评估HLX04-O治疗wAMD的有用性及清静性 。
信托通过复宏汉霖与亿胜生物的相助，HLX04-O的国际多中央临床试验有望加速推进，并依附相关研究效果在全球多个国家和地区实现上市，成为首批获得批准用于眼科相关疾病治疗的贝伐珠单抗，惠及全球众多眼科疾病患者 。未来，复宏汉霖也将一连引领立异生物药品的开发，依附已经建设起的完善的立异研发平台，一连高效地为全球患者提供可肩负的、疗效更好的治疗计划 。
关于湿性年岁相关性黄斑变性（wAMD）
年岁相关性黄斑变性（AMD）是导致晚年人视力损害和不可逆失明的主要缘故原由之一[1]，凭证天下卫生组织报告，全球约有3000万AMD患者，每年约有50万人由于AMD而致盲[2] 。AMD致盲患者中，以脉络膜新生血管（CNV）为特征的湿性年岁相关性黄斑变性（wAMD）比例高达90% 。随着晚年生齿比例的一直上升，wAMD已经成为一个日益严重的社会医学问题，保存着重大的未知足的临床需求[3] 。随着眼底治疗要领的突破与生长，抗VEGF药物已成为wAMD治疗的一线疗法[4]，贝伐珠单抗玻璃体注射治疗wAMD的有用性和清静性也已在多项临床研究中获得验证-6 。
关于HLX04-O
HLX04-O是复宏汉霖在自主研发的贝伐珠单抗生物类似药HLX04的基础上，凭证眼科用药的需求对HLX04的处方、规格和生产工艺举行优化，在活性成份稳固的基础上，开发的新的眼科制剂产品，拟用于wAMD的治疗 。通过可比性研究批注生产工艺和制剂处方的变换对药物制剂的质量、清静性和有用性未爆发倒运影响 。HLX04-O主要作用机制为：通过抑制VEGF与其位于内皮细胞上的受体Flt-1和KDR相团结，抑制其酪氨酸激酶信号通路激活，抑制内皮细胞增生，镌汰新生血管天生，从而治疗血管增生眼部疾病 。2021年1月和3月，HLX04-O用于湿性年岁相关性黄斑变性的治疗已划分获批准于澳大利亚、美国开展临床试验 。
关于复宏汉霖
复宏汉霖（2696.HK）是一家国际化的立异生物制药公司，致力于为全球患者提供可肩负的高品质生物药，产品笼罩肿瘤、自身免疫疾病、眼科疾病等领域，已在中国上市3款产品，在欧盟上市1款产品，2款产品获得中国上市注册申请受理 。自2010年建设以来，复宏汉霖已建成一体化生物制药平台，高效及立异的自主焦点能力贯串研发、生产及商业运营全工业链 。公司已建设完善高效的全球研发中央，凭证国际GMP标准举行生产和质量管控，位于上海徐汇的生产基地已获得中国和欧盟GMP认证 。
复宏汉霖前瞻性结构了一个多元化、高质量的产品管线，涵盖20多种立异单克隆抗体，并周全推进基于自有抗PD-1单抗HLX10的肿瘤免疫团结疗法 。继海内首个生物类似药汉利康®（利妥昔单抗）、中国首个自主研发的中欧双批单抗药物汉曲优®（曲妥珠单抗，欧盟商品名：Zercepac®）、公司首个自身免疫疾病治疗产品汉达远®（阿达木单抗）相继获批上市，公司HLX04贝伐珠单抗及HLX01利妥昔单抗类风湿枢纽炎新顺应症的上市注册申请也正在审评中 。公司亦同步就10个产品、8个团结治疗计划在全球规模内开展20多项临床试验，对外授权周全笼罩西欧主流生物药市场和众多新兴国家市场 。
Application for Clinical Trial of Henlius Bevacizumab HLX04-O Has Been Approved for the Treatment of wAMD in Latvia
Shanghai, China, April 20th, 2021 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the application for clinical trial of HLX04-O, a recombinant anti-VEGF humanized monoclonal antibody ophthalmic injection jointly developed by the Company and Essex has been approved by the State Agency of Medicines of Latvia, for the treatment of wet age-related macular degeneration (wAMD). This is the third clinical trial approval HLX04-O has received outside of China, after the approvals of clinical trial from the Therapeutic Goods Administration (TGA), Australia and U.S. Food and Drug Administration (FDA), and also the first clinical trial approval for HLX04-O in European Union(EU) countries. Besides, Henlius has successively submitted applications for clinical trial of HLX04-O in Hungary, Spain, Czech Republic and other EU countries, which are expected to be approved in the near future.
In October 2020, Henlius entered into a co-development and exclusive license agreement with Essex. With this collaboration, Henlius and Essex plan to conduct global multi-centre clinical trials of HLX04 in China, Australia, the European Union and the United States, and apply marketing authorization in different countries and regions around the globe based on the research results. Previously, a series of studies including non-clinical pharmacodynamics, safety pharmacology, repeat-dose toxicity, pharmacokinetics, toxicokinetics, immunotoxicity, immunogenicity and local irritation of HLX04-O vitreous injection in the treatment of wAMD have been carried out, initially proving the efficacy and safety of HLX04-O. The phase 3, global and multi-centre clinical study of HLX04-O is intended to commence in China, Australia, Russian Federation, Singapore, Spain and Poland in the near future to further evaluate the efficacy and safety of HLX04-O for the treatment of wAMD.
It is believed that Henlius and Essex will speed up the global multicentre clinical trials of HLX04-O and apply marketing authorization in different countries and regions around the globe based on the research results. HLX04-O has the potential to be one of the first bevacizumabs approved for ophthalmic diseases, benefiting more patients with eye diseases worldwide. Looking forward, Henlius will continue advancing the development of innovative biologics on the basis of its established and integrated innovation platform, underscoring its long-term commitment to providing affordable and effective therapies for patients worldwide.
About wAMD
Age-related macular degeneration is one of the leading causes of visual impairment and blindness in the elderly worldwide[1]. According to the World Health Organization (WHO), about 30 million people have suffered from AMD globally, and about half a million people become blind due to AMD each year[2]. Wet age-related macular degeneration (wAMD) is characterized by the formation of subretinal choroidal neovascularization (CNV) and is responsible for approximately 90% of cases of AMD-related blindness. Due to an aging population, wAMD has become a serious social medical problem and indicated a huge burden of unmet need[3]. With the development of treatment for fundus diseases, anti-VEGF drugs are becoming the first-line therapy for the management of wAMD[4], and the efficacy and safety of vitreous injection of bevacizumab for wAMD have been verified in multiple clinical studies-6.
About HLX04-O
HLX04-O is a new ophthalmic preparation product developed based on HLX04, a bevacizumab biosimilar independently developed by the Company, through optimizing the prescription, specifications and production processes of HLX04 according to the requirements of ophthalmic drugs, without changing the active ingredients, and is intended to be used for the treatment of wAMD. By means of comparability studies, it shows that changes in production processes and prescriptions of the preparation have no adverse impact on the quality, safety and efficacy of the pharmaceutical preparation. HLX04-O can inhibit VEGF’s binding to its receptor Flt-1(VEGFR-1) and KDR(VEGFR-2) on endothelial cells to inhibit the activation of its tyrosine kinase signaling pathway, inhibit endothelial cell proliferation and reduce angiogenesis, thereby treating eye diseases associated with angiogenesis. In January and March 2021, HLX04-O for the treatment of wAMD has been approved to commence clinical trials in Australia and the United States.
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 2 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 HLX10 (anti-PD-1 mAb) as backbone. Apart from the launched products 汉利康® (rituximab), the first China-developed biosimilar, 汉曲优® (trastuzumab, Zercepac® in the EU), the first China-developed mAb biosimilar approved both in China and in the EU and 汉达远® (adalimumab), the Company's first product indicated for autoimmune diseases, the NDA of HLX04 (bevacizumab) and HLX01 (rituximab) for the treatment of rheumatoid arthritis 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.
参考文献
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[4] Li X R , Liu J P . Recognition of anti-VEGF therapy base on the mechanism of VEGF in wet age-related macular degeneration[J]. Zhonghua Shiyan Yanke Zazhi/Chinese Journal of Experimental Ophthalmology, 2012, 30(4):289-292.
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[8] Kodjikian L, Souied EH, Mimoun G, Mauget-Fa?sse M, Behar -Cohen F, Decullier E, Huot L, Aulagner G; GEFAL Study Group. Ranibizumab versus Bevacizumab for Neovascular Agerelated Macular Degeneration: Results from the GEFAL Noninferiority Randomized Trial. Ophthalmology. 2013 Nov;120(11):2300-9.
[9] Krebs I, Schmetterer L, Boltz A, Told R, Vécsei-Marlovits V, Egger S, Sch?nherr U, Haas A, Ansari-Shahrezaei S, Binder S; MANTA Research Group. A randomized double-masked trial comparing the visual outcome after treatment with ranibizumab or bevacizumab in patients with neovascular age-related macular degeneration. Br J Ophthalmol. 2013 Mar;97(3):266-71.
[10] Berg K, Pedersen TR, Sandvik L, Bragadóttir R. Comparison of ranibizumab and bevacizumab for neovascular age-related macular degeneration according to LUCAS treat-and-extend protocol. Ophthalmology. 2015 Jan;122(1):146-52.
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