这是继顺利通过澳大利亚药品管理局(therapeutic goods administration,tga)的临床试验备案获批准于澳大利亚开展3期临床试验后,hlx04-o获得的又一境外临床试验许可。该项目将于近期启动一项分两部分开展的3期、全球、多中心临床研究,以进一步评估hlx04-o治疗wamd的有效性及安全性。根据临床研究方案,该研究将于中国大陆、澳大利亚、俄罗斯联邦、新加坡、西班牙、波兰等国家和地区共计入组388例病患。此前,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、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-o玻璃体注射有效和安全。



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。



henlius bevacizumab has received ind approval from us fda for the treatment of wamd

shanghai, china, march 19th, 2021 - shanghai henlius biotech, inc. (2696.hk) announced that the investigational new drug (ind) application of hlx04-o, a recombinant anti-vegf humanized monoclonal antibody ophthalmic injection jointly developed by the company and essex has been approved by the u.s. food and drug administration (fda) for the treatment of wet age-related macular degeneration (wamd). 

this is the second clinical trial approval hlx04-o has received outside of china , after the approval from the therapeutic goods administration, australia for initiating a phase 3 clinical trial in january 2021. the two-part, phase 3, global and multicentre clinical study of hlx04-o will be conducted to further evaluate the efficacy and safety of hlx04-o in patients with wamd in the near future. according to the protocol of the clinical study, there will be 388 patients from chinese mainand, australia, russian federation, singapore, spain and poland enroll to the study. 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.

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.

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 hlx04-o
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. 

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® (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. 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.


[1] 欧阳灵艺, 邢怡桥. 抗vegf药物在湿性年龄相关性黄斑变性中的应用进展[j]. 国际眼科杂志, 2020(1).

[2] resnikoff s, pascolini d, etya'ale d, kocur i, pararajasegaram r, pokharel gp, mariotti sp. global data on visual impairment in the year 2002. bull world health organ. 2004 nov;82(11):844-51.

[3] wong wl, su x, li x, et al. global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. lancet glob health. 2014;2(2):e106-116.

[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.

[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.