2023年2月10日，复宏汉霖（2696.HK）宣布公司与亿胜生物合作开发的重组抗血管内皮生长因子(Vascular endothelial growth factor, VEGF)人源化单克隆抗体注射液HLX04-O的国际多中心III期临床研究(NCT04740671)完成美国首例患者给药，拟用于湿性年龄相关性黄斑变性(wet age-related macular degeneration, wAMD)的治疗。该临床研究此前已在澳大利亚和欧盟完成首例患者给药。另一项在wAMD患者中开展的针对HLX04-O的III期临床研究亦于中国完成首例患者给药。
此研究是一项在湿性年龄相关性黄斑变性（wAMD）患者中开展的旨在比较HLX04-O与雷珠单抗的有效性和安全性的随机、双盲、阳性对照的全球III期研究。合格的受试者将以1:1的比例随机分为两组，分别于48周内每四周玻璃体腔内注射HLX04-O（1.25 mg）或雷珠单抗（0.5mg）。其主要目的为比较第36周HLX04-O与雷珠单抗在wAMD患者研究眼中的有效性，主要终点为第36周最佳矫正视力（Best corrected visual acuity，BCVA）较基线改善的平均字母数变化。次要目的包括评估其他疗效终点、安全性、耐受性以及药代动力学特征等。
HLX04-O是复宏汉霖利用基因工程技术构建的一款重组抗VEGF人源化单克隆抗体注射液，能够特异性结合血管内皮生长因子（Vascular endothelial growth factor, VEGF），阻断VEGF与内皮细胞上的受体Flt1（VEGFR-1）和KDR（VEGFR-2）结合，抑制其酪氨酸激酶信号通路的激活，进而抑制内皮细胞增生，减少新生血管生成，从而实现对wAMD等血管增生性眼部疾病的治疗。根据眼科用药需求，公司在贝伐珠单抗汉贝泰 的基础上保持活性成分不变，对处方、包装材料、规格和生产工艺等进行优化，开发了新的眼科制剂产品HLX04-O。可比性研究表明生产工艺和制剂处方的变更对药物制剂的质量、安全性和有效性未产生不利影响。
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除已完成首例患者给药的欧盟、澳大利亚及美国，HLX04-O亦获得包括新加坡在内的多个国家和地区的临床试验许可。复宏汉霖将携手亿胜生物持续推动HLX04-O的国际多中心III期临床试验，以期凭借相关研究结果实现HLX04-O在中国、澳大利亚、欧盟和美国等全球多个国家和地区上市，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，复宏汉霖也将积极推动创新生物药品的开发，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。
关于湿性年龄相关性黄斑变性
年龄相关性黄斑变性（AMD）是造成老年人视力损害和不可逆失明的主要原因之一[1]，根据世界卫生组织报告，全球约有3000万AMD患者，每年约有50万人因为AMD而致盲[2]。AMD致盲患者中，以脉络膜新生血管（Choroidal neovascularization，CNV）为特征的湿性年龄相关性黄斑变性（wAMD）比例高达90%。随着老年人口比例的不断上升，wAMD已经成为一个日益严重的社会医学问题，存在着巨大的未满足的临床需求[3]。随着眼底治疗方法的突破与发展，抗VEGF药物已成为wAMD的一线疗法[4]，贝伐珠单抗玻璃体注射治疗wAMD的有效性和安全性也已在多项临床研究中得到验证[5-11]。
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可负担的高品质生物药，产品覆盖肿瘤、自身免疫疾病、眼科疾病等领域，已在中国上市5款产品，在国际上市1款产品，18项适应症获批，1个上市注册申请获得中国药监局受理。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。公司已建立完善高效的全球创新中心，按照国际药品生产质量管理规范（GMP）标准进行生产和质量管控，不断夯实一体化综合生产平台，其中，上海徐汇基地已获得中国和欧盟GMP认证，松江基地（一）也已获得中国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H药汉斯状 的肿瘤免疫联合疗法。继国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，欧洲商品名：Zercepac ，澳大利亚商品名：Tuzucip 和Trastucip ）、汉达远 （阿达木单抗）和汉贝泰 （贝伐珠单抗）相继获批上市，创新产品汉斯状 （斯鲁利单抗）已获批用于治疗微卫星高度不稳定（MSI-H）实体瘤、鳞状非小细胞肺癌和广泛期小细胞肺癌，成为全球首个获批一线治疗小细胞肺癌的抗PD-1单抗，其食管鳞状细胞癌适应症的上市注册申请也正在审评中。公司亦同步就16个产品、12个免疫联合治疗方案在全球范围内开展20多项临床试验，对外授权全面覆盖欧美主流生物药市场和众多新兴市场。
First Patient in the US Dosed in a Global Multicentre Phase 3 Clinical Study of Henlius Bevacizumab for Treatment of Ophthalmic Diseases Shanghai, China, Feburary 10th, 2023 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first patient in the United States (US) was dosed in a global multicentre phase 3 clinical trial (NCT04740671) of HLX04-O, a recombinant anti-VEGF humanised monoclonal antibody injection jointly developed by the company and Essex, for the treatment of wet age-related macular degeneration (wAMD). Previously, the first patients in the European Union (EU) and Australia were dosed in the same global multicenter phase 3 clinical trial of HLX04-O. Meanwhile, the first patient has been dosed in another phase 3 clinical trial in China for HLX04-O for the treatment of wAMD.
This randomised, double-blind, active-controlled, global phase 3 study aims to compare the efficacy and safety of HLX04-O with ranibizumab in patients with wet age-related macular degeneration (wAMD). Eligible patients will be randomised 1:1 to receive intravitreal injection of HLX04-O (1.25 mg) or ranibizumab (0.5 mg) every 4 weeks for 48 weeks. The primary objective is to compare the efficacy of HLX04-O with ranibizumab at Week 36 in patient’s study eye with wAMD. The primary endpoint is the mean change from baseline in the best-corrected visual acuity (BCVA) at Week 36. Secondary objectives include the evaluation of other efficacy endpoints, safety, tolerability, and pharmacokinetic profiles.
HLX04-O is a recombinant anti-VEGF humanized monoclonal antibody injection constructed using genetic engineering technology independently developed by Henlius. 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 signalling pathway, inhibit endothelial cell proliferation and reduce angiogenesis, thereby treating eye diseases associated with angiogenesis. According to the requirements of ophthalmic drugs, the Company has developed HLX04-O which optimizes the prescription, specifications, and production processes of HANBEITAI, assuming that the active ingredients remain unchanged. Through a series of comparability analysis, it is proved that the changes in the production process and prescription of the preparation have no adverse impact on the quality, safety and efficacy of the preparation.
In addition to the EU and Australia, the clinical trial applications of HLX04-O had been approved in Singapore and other countries and regions. Through the cooperation with Essex, Henlius will speed up the global multicentre clinical trials of HLX04-O and apply marketing authorization in China, Australia, the EU, and the US around the globe based on the research results. HLX04-O has the potential to be one of the first bevacizumab approved for ophthalmic diseases, benefiting more patients with eye diseases worldwide. Looking forward, Henlius will continue advancing the development of innovative biologics based on 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[5-11].
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, 5 products have been launched in China, 1 approved for marketing in overseas markets, 15 indications approved worldwide, and 4 New Drug Applications (NDAs) 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 commercialization. It has established global innovation centers and Shanghai-based manufacturing facilities in line with global Good Manufacturing Practice (GMP), including Xuhui Plant certificated by China and the EU GMP and Songjiang First Plant certificated by China 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 HANSIZHUANG (anti-PD-1 mAb) as backbone. Apart from the launched products HANLIKANG (rituximab), the first China-developed biosimilar, HANQUYOU (trastuzumab, trade name in Europe: Zercepac ; trade names in Australia: Tuzucip and Trastucip , the first China-developed mAb biosimilar approved both in China and Europe, HANDAYUAN (adalimumab) and HANBEITAI (bevacizumab), the innovative product HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumors, squamous non-small cell lung cancer (sqNSCLC), and extensive-stage small cell lung cancer (ES-SCLC). Its NDA for the treatment of esophageal squamous cell carcinoma (ESCC) is under review. What"s more, Henlius has conducted over 20 clinical studies for 16 products and 12 immuno-oncology combination therapies, expanding its presence in major markets as well as emerging markets.
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[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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