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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2019, Vol. 39 Issue (3): 111-119    DOI: 10.13523/j.cb.20190314
行业分析     
全球单克隆抗体药物研发现状及发展趋势 *
高倩(),江洪,叶茂,郭文娟
中国科学院武汉文献情报中心 武汉 430071
Current Status and Trend of R&D of Monoclonal Antibodies
Qian GAO(),Hong JIANG,Mao YE,Wen-juan GUO
Wuhan Library,Chinese Academy of Sciences,Wuhan 430071, China
 全文: PDF(837 KB)   HTML
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”。

关键词: 单克隆抗体临床研发商业化交易    
Abstract:

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 the 133 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.

Key words: Monoclonal    antibodies    Clinical    R&D    Commercial    deal
收稿日期: 2018-09-18 出版日期: 2019-04-12
ZTFLH:  Q51  
基金资助: * 湖北省技术创新专项(软科学研究类)资助项目(2018ADC003)
通讯作者: 高倩     E-mail: gaoq@mail.whlib.ac.cn
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引用本文:

高倩,江洪,叶茂,郭文娟. 全球单克隆抗体药物研发现状及发展趋势 *[J]. 中国生物工程杂志, 2019, 39(3): 111-119.

Qian GAO,Hong JIANG,Mao YE,Wen-juan GUO. Current Status and Trend of R&D of Monoclonal Antibodies. China Biotechnology, 2019, 39(3): 111-119.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.20190314        https://manu60.magtech.com.cn/biotech/CN/Y2019/V39/I3/111

图1  全球单克隆抗体药物处于研发和商业化各阶段的数量分布
图2  单克隆抗体药物数量TOP10的国家/地区
图3  各细分种类已上市单克隆抗体药物的数量分布
排名 主要靶向作用 数量(个)
1 HER2酪氨酸激酶受体抑制剂 111
2 TNF-α配体抑制剂 109
3 TNF结合剂 90
4 B淋巴细胞CD20抗原抑制剂 80
5 程序性细胞死亡蛋白-1抑制剂 77
6 VEGF配体抑制剂 75
7 程序性细胞死亡蛋白-1配体抑制剂 68
8 表皮生长因子受体拮抗剂 56
9 HER2酪氨酸激酶受体调节剂 40
10 CD3调节剂 38
表1  药物主要靶向作用数量TOP10
排名 药品名称(商品名) 公司 2017年销售额(亿美元)
总额 美国
(US)
欧洲
(EU)
日本
(JP)
亚洲
(ASI)
其他国家
/地区
1 Adalimumab (Humira) AbbVie Inc Eisai Co Ltd 187.67 123.61 3.4 60.66
2 Infliximab (Remicade) Johnson & Johnson Merck & Co Inc Mitsubishi Tanabe Pharma Corp 77.55 50.88 8.37 6.03 12.27
3 Rituximab(Rituxan;MabThera) Roche Holding AG 75.04 41.98 17.16 2.97 12.92
4 Trastuzumab (Herceptin) Roche Holding AG 71.24 27.39 21.56 2.99 19.28
5 Bevacizumab (Avastin) Roche Holding AG 67.93 29.39 18.03 8.29 12.19
6 Nivolumab (Opdivo) Ono Pharmaceutical Co Ltd
Bristol-Myers Squibb Co
58.86 31.02 9.38 18.46
7 Ustekinumab (Stelara) Johnson & Johnson 40.11 27.67 12.44
8 Denosumab (Pralia) Amgen Inc Daiichi Sankyo Co Ltd 38.31 24.29 2.88 11.14
9 Pembrolizumab (Keytruda) Merck & Co Inc 38.09 23.09 15
10 Ranibizumab (Lucentis) Roche Holding AG Novartis AG 33.24 14.36 18.88
11 Eculizumab (Soliris) Alexion Pharmaceuticals Inc 31.44 12.35 9.86 3.28 5.95
12 Golimumab (Simponi) Johnson & Johnson Merck & Co Inc Mitsubishi Tanabe Pharma Corp 28.76 9.54 8.19 2.24 8.79
13 Omalizumab (Xolair) Roche Holding AG Novartis AG 26.89 17.69 9.2
14 Pertuzumab (Perjeta) Roche Holding AG 22.3 10.28 7.79 1.21 3
15 Secukinumab (Cosentyx) Novartis AG 20.71 12.75 7.96
16 Natalizumab (Tysabri) Biogen Inc 19.73 11.13 8.59
17 Tocilizumab (Actemra) Roche Holding AG 19.56 7.67 3.08 6.4
18 Vedolizumab (Entyvio) Takeda Pharmaceutical Co Ltd 18.52 12.29 5.53 0.69
19 Certolizumab pegol (Cimzia) Astellas Pharma Inc UCB SA 16.77 10.36 4.17 0.69 1.53
20 Cetuximab (Erbitux) Eli Lilly & Co Merck KGaA 16.09 6.45 5.04 4.58
21 Ipilimumab (Yervoy) Bristol-Myers Squibb Co 12.44 9.08 3.36
22 Daratumumab (Darzalex) Johnson & Johnson 12.42 8.84 3.58
表2  2017年销售额10亿美元以上的单克隆抗体药物汇总
表3  2017年单克隆抗体药物商业化交易金额TOP10
[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.
doi: 10.1016/j.biotechadv.2016.07.004 pmid: 27460206
[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.
doi: 10.1097/00002820-200308000-00012 pmid: 12907618
[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.
doi: 10.1056/NEJM200103223441207
[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.
doi: 10.1136/ard.58.2008.i70 pmid: 1766582
[6] Scallon B J, Moore M A, Trinh H , et al. Chimeric anti- TNF- alpha monoclonal antibody cA2 binds recombinant transmembrane TNF alpha and activates immune effector functions. Cytokine, 1995,7(3):251-259.
doi: 10.1006/cyto.1995.0029
[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.
doi: 10.2165/11201110-000000000-00000
[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.
doi: 10.1517/14740338.2014.955848 pmid: 25244502
[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.
doi: 10.1056/NEJMoa1412082 pmid: 25399552
[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 2 trial. Archives of Dermatology, 2008,144(2):200-207.
doi: 10.1001/archdermatol.2007.63 pmid: 18283176
[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.
doi: 10.2147/BTT.S57359 pmid: 4507456
[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.
doi: 10.11877/j.issn.1672-1535.2017.15.08.06
Tang J L, Huang J . The treatment progress on PD-1/PD-L1 immune checkpoint inhibitor treating advanced colorectal cancer. Oncology Progress, 2017,15(8):872-875.
doi: 10.11877/j.issn.1672-1535.2017.15.08.06
[14] Rosenfeld P J, Rich R M, Lalwani G A . Ranibizumab: Phase III clinical trial results. Ophthalmology Clinics of North America, 2006,19(3):361-372.
doi: 10.1016/j.ohc.2006.05.009 pmid: 16935211
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