全球单克隆抗体药物研发现状及发展趋势
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摘要
单克隆抗体药物以其独特的作用机制及高效性,在恶性肿瘤和自身免疫疾病的治疗中发挥了不可估量的重要作用,成为全球的研发热点。基于科睿唯安旗下的Cortellis数据库,采用定量分析和专家智慧相结合的方法,从总体研发和商业化现状、主要国家/地区、技术和种类、靶点及作用机制、市场份额、产品交易多个维度展现出全球单克隆抗体药物的研发和商业化全景。分析结果显示:全球已上市的单克隆抗体药物有133个,其中已上市的人源化单克隆抗体药物占已上市的单克隆抗体药物总数的37. 6%。作用靶点主要集中在HER、TNF、CD20、PD-1/L1、VEGF以及CD3,其中作为HER2酪氨酸激酶受体抑制剂的药物数量最多。美国在单克隆抗体药物研发和商业化方面遥遥领先,中国在研和上市的单抗隆抗体药物总数排名第二,但中国上市的单抗隆抗体药物数量仅8个。2017年销售额高于10亿美元的单克隆抗体药物有22个。全球单克隆抗体药物的交易数量共有1 408次,药物开发与商业化许可是最主要的交易方式。未来,单克隆抗体药物的发展趋势将朝着新靶点、新适应症和新用药方案的方向发展,将会产生更多"重磅炸弹药物"。
Monoclonal antibodies have played an inestimable role in the treatment of cancer and autoimmune diseases with their unique mechanism and high efficiency,which have become the focus of research in biopharmaceutics. In this paper, all the data was extracted from Clarivate via Cortellis. Through the combination of quantitative data analysis and expert wisdom,the competitive landscape of monoclonal antibodies was presented from various dimensions,including the overall trend of R&D and industrialization,focus countries,technology and drug categories,targets,market share and commercial deal. The results showed that among the133 kinds of launched monoclonal antibodies recently,37. 6% of them belonged to humanized monoclonal antibodies. HER,TNF,CD20,PD-1/L1,VEGF and CD3 were the "hot"antibody target molecule,of the total number of target-based actions which was the most numerous in HER2 tyrosine kinase receptor inhibitor. The total volume of monoclonal antibodies in China ranked second to the United States. But there were only 8 monoclonal antibodies approved in China,which was far below the level of United States. There were 22 launched monoclonal antibodies achieved annual sales over $1 biliion in 2017. Access to 1408 monoclonal antibodies deal records,drug development/commercial license was the primary agreement type. In the future,the development trend of monoclonal antibodies will be focused on new targets,new indications and new therapeutic schemes,and then more "blockbuster drugs" will be produced.
Monoclonal antibodies have played an inestimable role in the treatment of cancer and autoimmune diseases with their unique mechanism and high efficiency,which have become the focus of research in biopharmaceutics. In this paper, all the data was extracted from Clarivate via Cortellis. Through the combination of quantitative data analysis and expert wisdom,the competitive landscape of monoclonal antibodies was presented from various dimensions,including the overall trend of R&D and industrialization,focus countries,technology and drug categories,targets,market share and commercial deal. The results showed that among the133 kinds of launched monoclonal antibodies recently,37. 6% of them belonged to humanized monoclonal antibodies. HER,TNF,CD20,PD-1/L1,VEGF and CD3 were the "hot"antibody target molecule,of the total number of target-based actions which was the most numerous in HER2 tyrosine kinase receptor inhibitor. The total volume of monoclonal antibodies in China ranked second to the United States. But there were only 8 monoclonal antibodies approved in China,which was far below the level of United States. There were 22 launched monoclonal antibodies achieved annual sales over $1 biliion in 2017. Access to 1408 monoclonal antibodies deal records,drug development/commercial license was the primary agreement type. In the future,the development trend of monoclonal antibodies will be focused on new targets,new indications and new therapeutic schemes,and then more "blockbuster drugs" will be produced.
引文
[1]任会琴,张永莉,吴剑涓,等.单克隆抗体药物在抗血栓治疗中的应用及研究进展.中国医院药学杂志,2010,30(09):787-789.Ren H Q,Zhang Y L,Wu J J.Application and research advance of monoclonal antibodies in antithrombotic therapy.Chinese Journal of Hospital Pharmacy,2010,30(09):787-789.
[2]Rodgers K R,Chou R C.Therapeutic monoclonal antibodies and derivatives:Historical perspectives and future directions.Biotechnology Advances,2016,34(6):1149-1158.
[3]Barbacci E G,Pustilnik L R,Rossi A M,et al.The biological and biochemical effects of CP-654577,a selective erbB2 kinase inhibitor,on human breast cancer cells.Cancer Research,2003,63(15):4450-4459.
[4]Choy E H,Panayi G S.Cytokine pathways and joint inflammation in rheumatoid arthritis.New England Journal of Medicine,2001,344(12):907-916.
[5]Kempeni J.Preliminary results of early clinical trials with the fully human anti-TNF monoclonal antibody D2E7.Annals of The Rheumatic Diseases,1999,58(Suppl 1):170-172.
[6]Scallon B J,Moore M A,Trinh H,et al.Chimeric anti-TNF-alpha monoclonal antibody c A2 binds recombinant transmembrane TNF alpha and activates immune effector functions.Cytokine,1995,7(3):251-259.
[7]Keating G M.Rituximab:A review of its use in chronic lymphocytic leukaemia,low-grade or follicular lymphoma and diffuse large B-cell lymphoma.Drugs,2010,70(11):1445-1476.
[8]Abdel-Rahman O,ElHalawani H.Adjuvant systemic treatment for elderly breast cancer patients;addressing safety concerns.Expert Opinion on Drug Safety,2014,13(11):1443-1467.
[9]Wildiers H,Guetens G,De Boeck G,et al.Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11.British Journal of Cancer,2003,88(12):1979-1986.
[10]Robert C,Long G V,Brady B,et al.Nivolumab in previously untreated melanoma without BRAF mutation.The New England Journal of Medicine,2015,372(4):320-330.
[11]Kimball A B,Gordon K B,Langley R G,et al.Safety and efficacy of ABT-874,a fully human interleukin 12/23 monoclonal antibody,in the treatment of moderate to severe chronic plaque psoriasis:Results of a randomized,placebo-controlled,phase 2trial.Archives of Dermatology,2008,144(2):200-207.
[12]Singh A S,Chawla N S,Chawla S P.Giant-cell tumor of bone:Treatment options and role of denosumab.Biologics:Targets&Therapy,2015,9:69-74.
[13]汤佳琳,黄镜.PD-1/PD-L1免疫检查点抑制剂在晚期结直肠癌的药物治疗进展.癌症进展,2017,15(8):872-875.Tang J L,Huang J.The treatment progress on PD-1/PD-L1immune checkpoint inhibitor treating advanced colorectal cancer.Oncology Progress,2017,15(8):872-875.
[14]Rosenfeld P J,Rich R M,Lalwani G A.Ranibizumab:Phase IIIclinical trial results.Ophthalmology Clinics of North America,2006,19(3):361-372.
[2]Rodgers K R,Chou R C.Therapeutic monoclonal antibodies and derivatives:Historical perspectives and future directions.Biotechnology Advances,2016,34(6):1149-1158.
[3]Barbacci E G,Pustilnik L R,Rossi A M,et al.The biological and biochemical effects of CP-654577,a selective erbB2 kinase inhibitor,on human breast cancer cells.Cancer Research,2003,63(15):4450-4459.
[4]Choy E H,Panayi G S.Cytokine pathways and joint inflammation in rheumatoid arthritis.New England Journal of Medicine,2001,344(12):907-916.
[5]Kempeni J.Preliminary results of early clinical trials with the fully human anti-TNF monoclonal antibody D2E7.Annals of The Rheumatic Diseases,1999,58(Suppl 1):170-172.
[6]Scallon B J,Moore M A,Trinh H,et al.Chimeric anti-TNF-alpha monoclonal antibody c A2 binds recombinant transmembrane TNF alpha and activates immune effector functions.Cytokine,1995,7(3):251-259.
[7]Keating G M.Rituximab:A review of its use in chronic lymphocytic leukaemia,low-grade or follicular lymphoma and diffuse large B-cell lymphoma.Drugs,2010,70(11):1445-1476.
[8]Abdel-Rahman O,ElHalawani H.Adjuvant systemic treatment for elderly breast cancer patients;addressing safety concerns.Expert Opinion on Drug Safety,2014,13(11):1443-1467.
[9]Wildiers H,Guetens G,De Boeck G,et al.Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11.British Journal of Cancer,2003,88(12):1979-1986.
[10]Robert C,Long G V,Brady B,et al.Nivolumab in previously untreated melanoma without BRAF mutation.The New England Journal of Medicine,2015,372(4):320-330.
[11]Kimball A B,Gordon K B,Langley R G,et al.Safety and efficacy of ABT-874,a fully human interleukin 12/23 monoclonal antibody,in the treatment of moderate to severe chronic plaque psoriasis:Results of a randomized,placebo-controlled,phase 2trial.Archives of Dermatology,2008,144(2):200-207.
[12]Singh A S,Chawla N S,Chawla S P.Giant-cell tumor of bone:Treatment options and role of denosumab.Biologics:Targets&Therapy,2015,9:69-74.
[13]汤佳琳,黄镜.PD-1/PD-L1免疫检查点抑制剂在晚期结直肠癌的药物治疗进展.癌症进展,2017,15(8):872-875.Tang J L,Huang J.The treatment progress on PD-1/PD-L1immune checkpoint inhibitor treating advanced colorectal cancer.Oncology Progress,2017,15(8):872-875.
[14]Rosenfeld P J,Rich R M,Lalwani G A.Ranibizumab:Phase IIIclinical trial results.Ophthalmology Clinics of North America,2006,19(3):361-372.