美國fda批准臨床,復宏漢霖貝伐珠單抗眼科適應症再獲境外臨床試驗許可-凯发k8娱乐app下载

美國fda批准臨床,復宏漢霖貝伐珠單抗眼科適應症再獲境外臨床試驗許可-凯发k8娱乐app下载

2021-03-22

美國fda批准臨床,復宏漢霖貝伐珠單抗眼科適應症再獲境外臨床試驗許可

2021年3月19日,複宏漢霖(2696.hk)宣佈公司與億勝生物合作開發的重組抗vegf人源化單克隆抗躰眼用注射液hlx04-o的臨床試驗申請獲美國食品藥品管理局(fda)準予,擬用於濕性年齡相關性黃斑變性(wamd)的治療。

這是繼順利通過澳大利亞藥品管理局(therapeutic goods administration,tga)的臨床試驗備案獲批准於澳大利亞開展3期臨床試驗後,hlx04-o獲得的又一境外臨床試驗許可。 該項目將於近期啟動一項分兩部分開展的3期、全球、多中心臨床研究,以進一步評估hlx04-o治療wamd的有效性及安全性。 根據臨床研究方案,該研究將於中國大陸、澳大利亞、俄羅斯聯邦、新加坡、西班牙、波蘭等國家和地區共計入組388例病患。 此前,複宏漢霖已開展了hlx04-o玻璃體注射治療wamd的非臨床藥效學、安全藥理學、重複給藥毒性、藥代動力學、毒代動力學、免疫毒性、免疫原性、局部刺激性試驗等相關研究,在臨床前試驗中初步證明了hlx04-o玻璃體注射有效和安全。


年齡相關性黃斑變性(amd)是導致老年人視力損害和不可逆失明的主要原因之一[1],根據世界衛生組織報告,全球約有3000萬amd患者,每年約有50萬人因為amd而致盲[2]。 amd致盲患者中,以脈絡膜新生血管(cnv)為特徵的濕性年齡相關性黃斑變性(wamd)比例高達90%。 隨著老年人口比例的不斷上升,wamd已經成為一個日益嚴重的社會醫學問題,存在著巨大的未滿足的臨床需求[3]。 隨著眼底治療方法的突破與發展,抗vegf藥物已成為wamd治療的一線療法[4],貝伐珠單抗玻璃體注射治療wamd的有效性和安全性也已在多項臨床研究中得到驗證-6。

相信通過複宏漢霖與億勝生物的合作,hlx04-o的國際多中心臨床試驗有望加速推進,並憑藉相關研究結果在全球多個國家和地區實現上市,成為首批獲得批准用於眼科相關疾病治療的貝伐珠單抗,惠及全球眾多眼科疾病患者。 未來,複宏漢霖也將持續引領創新生物藥品的開發,憑藉已經建立起的完善的創新研發平臺,持續高效地為全球患者提供可負擔的、療效更好的治療方案。

關於hlx04-o
hlx04-o是複宏漢霖利用基因工程技術構建的一款重組抗vegf人源化單克隆抗躰眼用注射液,能够特异性結合血管內皮生長因數(vascular endothelial growth factor,vegf),阻斷vegf與內皮細胞上的受體flt1(vegfr-1)和kdr(vegfr-2)結合,抑制其酪氨酸激酶訊號通路的啟動,進而抑制內皮細胞增生,减少新生血管生成, 從而實現對wamd等血管增生眼部疾病的治療。 根據眼科用藥需求,公司在貝伐珠單抗hlx04的基礎上保持活性成分不變,對處方、包裝材料、規格和生產工藝等進行優化,開發了新的眼科製劑產品hlx04-o。

關於複宏漢霖
複宏漢霖(2696.hk)是一家國際化的創新生物製藥公司,致力於為全球患者提供質高價優的創新生物藥,產品覆蓋腫瘤、自身免疫疾病、眼科疾病等領域。 自2010年成立以來,複宏漢霖已建成一體化生物製藥平臺,高效及創新的自主核心能力貫穿研發、生產及商業運營全產業鏈。 公司在全球已建立完善的研發中心,按照國際gmp標準進行生產和質量管控,位於上海徐匯的生產基地已獲得中國和歐盟gmp認證。

複宏漢霖前瞻性佈局了一個多元化、高品質的產品管線,涵蓋20多種創新單克隆抗躰,並全面推進基於自有抗pd-1單抗hlx10的腫瘤免疫聯合療法。 截至目前,公司已成功上市3個單抗生物藥,包括國內首個生物類似藥漢利康 ® (利妥昔單抗)、首個中歐雙批的國產生物類似藥漢曲優 ® (曲妥珠單抗,歐盟商品名:zercepac ®) 以及公司首個自身免疫疾病治療產品漢達遠 ® (阿達木單抗)。 此外,hlx04貝伐珠單抗及hlx01利妥昔單抗類風濕關節炎新適應症的上市註冊申請正在審評中,公司亦同步就10個產品、8個聯合治療方案於全球範圍內開展20多項臨床試驗,產品對外授權全面覆蓋歐美主流生物藥市場和眾多新興國家市場。

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: 漢利康 ® (rituximab), the first china-developed biosimilar, 漢曲優 ® (trastuzumab, zercepac® in the eu), the first china-developed mab biosimilar approved both in china and in the eu and 漢達遠 ® (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.

參考文獻

[1] 歐陽靈藝,邢怡橋. 抗vegf藥物在濕性年齡相關性黃斑變性中的應用進展[j]. 國際眼科雜誌,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.