復宏漢霖貝伐珠單抗新應用,眼科適應症獲澳大利亞臨床批准-凯发k8娱乐app下载

復宏漢霖貝伐珠單抗新應用,眼科適應症獲澳大利亞臨床批准-凯发k8娱乐app下载

2021-02-03

復宏漢霖貝伐珠單抗新應用,眼科適應症獲澳大利亞臨床批准

2021年1月29日,复宏汉霖(2696.hk)宣布公司与亿胜生物合作开发的重组抗vegf人源化单克隆抗体眼用注射液hlx04-o通过了澳大利亚药品管理局(therapeutic goods administration,tga)的临床试验备案,被批准于澳大利亚开展3期临床研究,拟用于湿性年龄相关性黄斑变性(wamd)的治疗。该项目在澳大利亚的3期临床研究将于近期启动。

年龄相关性黄斑变性(amd)是导致老年人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(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-6。


hlx04-o是复宏汉霖利用基因工程技术构建的一款重组抗vegf人源化单克隆抗体眼用注射液,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等血管增生眼部疾病的治疗。根据眼科用药需求,公司在贝伐珠单抗hlx04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。

目前,复宏汉霖已开展hlx04-o玻璃体注射治疗wamd的非临床药效学、安全药理学、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,在临床前试验中初步证明了hlx04玻璃体注射有效和安全。接下来,一项两部分开展的3期、全球、多中心研究将在澳大利亚启动,以进一步评估hlx04-o治疗wamd的有效性及安全性。

相信通过复宏汉霖与亿胜生物的合作,hlx04-o在中国、澳大利亚、欧盟、美国等国家和地区的国际多中心临床试验有望加速启动,并凭借相关研究结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,复宏汉霖也将持续引领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 bevacizumab has received clinical trial approval in australia

shanghai, china, jan, 29th, 2021 - shanghai henlius biotech, inc. (2696.hk) announced that the filing of clinical trial for hlx04-o, a recombinant anti-vegf humanized monoclonal antibody ophthalmic injection, for the treatment of wet age-related macular degeneration (wamd) has been approved by the therapeutic goods administration, australia. the phase 3 clinical study of the project in australia is intended to be initiated in the near future.

age-related macular degeneration is one of the leading causes of 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.

hlx04-o is a recombinant anti-vegf humanized monoclonal antibody ophthalmic 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 signaling 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 hlx04, 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. 

as of now, 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. in the near future, a two-part, phase 3, global, multicentre study of hlx04-o will be initiated in australia to further evaluate the efficacy and safety in treatment of wamd.

it is believed that henlius and essex will speed up the global multicentre clinical trials of hlx04-o 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. 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 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

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[5] tufail a, patel pj, egan c, hykin p, da cruz l, gregor z, dowler j, majid ma, bailey c, mohamed q, johnston r, bunce c, xing w; abc trial investigators. bevacizumab for neovascular age related macular degeneration (abc trial): multicentre randomized double masked study. bmj. 2010 jun 9;340:c2459.
[6] martin df, maguire mg, ying gs, grunwald je, fine sl, jaffe gj. ranibizumab and bevacizumab for neovascular age-related macular degeneration. n engl j med. 2011 may 19;364(20):1897-908. 
[7] chakravarthy u, harding sp, rogers ca, downes sm, lotery aj, wordsworth s, reeves bc. ranibizumab versus bevacizumab to treat neovascular age-related macular degeneration: one-year findings from the ivan randomized trial. ophthalmology. 2012 jul;119(7):1399-411.
[8] kodjikian l, souied eh, mimoun g, mauget-faÿsse 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, schönherr 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.
[11] schauwvlieghe am, dijkman g, hooymans jm, verbraak fd, hoyng cb, dijkgraaf mg,peto t, vingerling jr, schlingemann ro. comparing the effectiveness of bevacizumab to ranibizumab in patients with exudative age-related macular degeneration. the bramd study. plos one. 2016 may 20;11(5):e0153052.