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].
【参考文献】
[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.