Welcome to visit Zhongnan Medical Journal Press Series journal website!

Home Articles Vol 28,2024 No.2 Detail

Research progress of novel anti-VEGF therapy in the treatment of neovascular age-related macular degeneration with novel drugs

Published on Nov. 08, 2024Total Views: 422 times Total Downloads: 39 times Download Mobile

Author: HOU Huimin 1, 2, 3 CHANG Xueke 1, 2, 3 ZHANG Leying 2, 3, 4 SONG Zongming 1, 2, 3, 4

Affiliation: 1. Department of Ophthalmology, Zhengzhou University People's Hospital, Zhengzhou 450003, China 2. Department of Ophthalmology, Henan Provincial People's Hospital, Zhengzhou 450003, China 3. Department of Ophthalmology, Henan Eye Hospital, Zhengzhou 450003, China 4. Department of Ophthalmology, Henan University People's Hospital, Zhengzhou 450003, China

Keywords: Neovascular age-related macular degeneration Pathogenesis Novel drugs

DOI: 10.12173/j.issn.2097-4922.202404064

Reference: HOU Huimin, CHANG Xueke, ZHANG Leying, SONG Zongming.Research progress of novel anti-VEGF therapy in the treatment of neovascular age-related macular degeneration with novel drugs[J].Yaoxue QianYan Zazhi,2024, 28(2):268-277.DOI: 10.12173/j.issn.2097-4922.202404064.[Article in Chinese]

  • Abstract
  • Full-text
  • References
Abstract

Neovascular age-related macular degeneration (nAMD) is one of the main causes of visual impairment in middle-aged and elderly people, and the incidence of this disease is rising in our country. The imbalance of vascular endothelial growth factor (VEGF) is the main cause of nAMD. In addition, various growth factors other than VEGF, complement system activation, inflammatory factors, autophagy, and many other factors are involved in the pathogenesis of nAMD. Currently, intravitreal injection of anti-VEGF drugs has become the first-line regimen for the treatment of nAMD, but there are still many shortcomings of the current anti-VEGF drugs, such as multiple potential risks of frequent injections, insensitive responses in some patients, and low compliance of the patients, etc. Therefore, the search for novel therapeutic agents has become urgent. This article provides a review of new developments in the study of novel drugs newly marketed and undergoing clinical trials for the treatment of nAMD, with the aim of seeking longer-lasting and better-acting therapeutic regimens, as well as exploring new therapeutic targets, to further inform the advancement of innovation and development of therapeutic strategies for nAMD.

Full-text
Please download the PDF version to read the full text: download
References

1.Guymer RH, Campbell TG. Age-related macular degeneration[J]. Lancet, 2023, 401(10386): 1459-1472. DOI: 10.1016/S0140-6736(22)02609-5.

2.Ricci F, Bandello F, Navarra P, et al. Neovascular age-related macular degeneration: therapeutic management and new-upcoming approaches[J]. Int J Mol Sci, 2020, 21(21): 8242. DOI: 10.3390/ijms21218242.

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[J]. Lancet Glob Health, 2014, 2(2): e106-e116. DOI: 10.1016/S2214-109X(13)70145-1.

4.李康琪, 李龙孝, 王婧, 等. 抗VEGF药物用于年龄相关性黄斑变性研究的文献计量分析[J]. 药物流行病学杂志, 2020, 29(1): 61-66. [Li KQ, Li LX, Wang  J, et al. Bibliometric analysis of anti-VEGF drugs used in age-related macular degeneration[J]. Chinese Journal of Pharmacoepidemiology, 2020, 29(1): 61-66.] DOI: 10.19960/j.cnki.issn1005-0698.2020.01.012.

5.Spaide RF, Jaffe GJ, Sarraf D, et al. Consensus nomenclature for reporting neovascular age-related macular degeneration data: consensus on neovascular age-related macular degeneration nomenclature study group[J]. Ophthalmology, 2020, 127(5): 616-636. DOI: 10.1016/j.ophtha.2019.11.004.

6.Al-Khersan H, Hussain RM, Ciulla TA, et al. Innovative therapies for neovascular age-related macular degeneration[J]. Expert Opin Pharmacother, 2019, 20(15): 1879-1891. DOI: 10.1080/14656566.2019.1636031.

7.孙子雯, 汤垟, 陈晨, 等. 年龄相关性黄斑变性的发病机制与抗氧化治疗[J]. 国际眼科杂志, 2020, 20(3): 468-471. [Sun ZW, Tang Y, Chen C, et al. The pathogenesis and antioxidant therapy of age-related macular degeneration[J]. International Eye Science, 2020, 20(3): 468-471.] DOI: 10.3980/j.issn.1672-5123. 2020.3.13.

8.Stahl A. The diagnosis and treatment of age-related macular degeneration[J]. Dtsch Arztebl Int, 2020, 117(29-30): 513-520. DOI: 10.3238/arztebl.2020.0513.

9.Apte RS, Chen DS, Ferrara N. VEGF in signaling and disease: beyond discovery and development[J]. Cell, 2019, 176(6): 1248-1264. DOI: 10.1016/j.cell.2019.01.021.

10.Uemura A, Fruttiger M, D'Amore PA, et al. VEGFR1 signaling in retinal angiogenesis and microinflammation[J]. Prog Retin Eye Res, 2021, 84: 100954. DOI: 10.1016/j.preteyeres.2021.100954.

11.Apte RS. Pegaptanib sodium for the treatment of age-related macular degeneration[J]. Expert Opin Pharmacother, 2008, 9(3): 499-508. DOI: 10.1517/ 14656566.9.3.499.

12.郑翰然, 胡艳红, 叶照达. wARMD抗VEGF治疗应答不良的影响因素及靶向周细胞的治疗策略[J]. 国际眼科杂志, 2023, 23(12): 1998-2002. [Zheng HR, Hu YH, Ye ZD. Influencing Factors of adverse response to wARMD anti-VEGF therapy and therapeutic strategies targeting pericytes[J]. International Eye Science, 2019, 23(12): 1998-2002.] DOI: 10.3980/j.issn.1672-5123.2023.12.12.

13.韩梅, 李岩峰, 葛明. Aflibercept治疗湿性年龄相关黄斑变性的研究概述[J]. 中国药师, 2012, 15(6): 884-886. [Han M, Li YF, Ge M. Study summary of Aflibercept in the treatment of wet age-related macular degeneration[J]. China Pharmacist, 2012, 15(6): 884-886.] DOI: 10.3969/j.issn.1008-049X.2012.06.054.

14.王艳, 朱少惠, 杨佳宁, 等. 雷珠单抗治疗糖尿病黄斑水肿的快速卫生技术评估[J]. 中国药师, 2022, 25(10): 1763-1768. [Wang Y, Zhu SH, Yang JN, et al. Rapid health technology evaluation of Leizumab in the treatment of diabetic macular edema[J]. China Pharmacist, 2022, 25(10): 1763-1768.] DOI: 10.19962/j.cnki.issn1008-049X.2022.10.013.

15.Arrigo A, Bandello F. Molecular features of classic retinal drugs, retinal therapeutic targets and emerging treatments[J]. Pharmaceutics, 2021, 13(7): 1102. DOI: 10.3390/pharmaceutics13071102.

16.Kuo BL, Singh RP. Brolucizumab for the treatment of diabetic macular edema[J]. Curr Opin Ophthalmol, 2022, 33(3): 167-173. DOI: 10.1097/ICU.0000000000000849.

17.Markham A. Brolucizumab: first approval[J]. Drugs, 2019, 79(18): 1997-2000. DOI: 10.1007/s40265-019-01231-9.

18.Dugel PU, Jaffe GJ, Sallstig P, et al. Brolucizumab versus aflibercept in participants with neovascular age-related macular degeneration: a randomized trial[J]. Ophthalmology, 2017, 124(9): 1296-1304. DOI: 10.1016/j.ophtha.2017.03.057.

19.Dugel PU, Singh RP, Koh A, et al. HAWK and HARRIER: ninety-six-week outcomes from the phase 3 trials of brolucizumab for neovascular age-related macular degeneration[J]. Ophthalmology, 2021, 128(1): 89-99. DOI: 10.1016/j.ophtha.2020.06.028.

20.Baumal CR, Sørensen TL, Karcher H, et al. Efficacy and safety of brolucizumab in age-related macular degeneration: a systematic review of real-world studies[J]. Acta Ophthalmol, 2023, 101(2): 123-139. DOI: 10.1111/aos.15242.

21.Wolf AT, Harris A, Oddone F, et al. Disease progression pathways of wet AMD: opportunities for new target discovery[J]. Expert Opin Ther Targets, 2022, 26(1): 5-12. DOI: 10.1080/14728222.2022.2030706.

22.Hussain RM, Shaukat BA, Ciulla LM, et al. Vascular endothelial growth factor antagonists: promising players in the treatment of neovascular age-related macular degeneration[J]. Drug Des Devel Ther, 2021, 15: 2653-2665. DOI: 10.2147/DDDT.S295223.

23.Jackson TL, Slakter J, Buyse M, et al. A randomized controlled trial of OPT-302, a VEGF-C/D inhibitor for neovascular age-related macular degeneration[J]. Ophthalmology, 2023, 130(6): 588-597. DOI: 10.1016/j.ophtha.2023.02.001.

24.Moisseiev E, Loewenstein A. Abicipar pegol-a novel anti-VEGF therapy with a long duration of action[J]. Eye (Lond), 2020, 34(4): 605-606. DOI: 10.1038/s41433-019-0584-y.

25.Samanta A, Aziz AA, Jhingan M, et al. Emerging therapies in neovascular age-related macular degeneration in 2020[J]. Asia Pac J Ophthalmol (Phila), 2020, 9(3): 250-259. DOI: 10.1097/APO.0000000000000291.

26.Hussain RM, Neiweem AE, Kansara V, et al. Tie-2/Angiopoietin pathway modulation as a therapeutic strategy for retinal disease[J]. Expert Opin Investig Drugs, 2019, 28(10): 861-869. DOI: 10.1080/13543784.2019.1667333.

27.Shirley M. Faricimab: first approval[J]. Drugs, 2022, 82(7): 825-830. DOI: 10.1007/s40265-022-01713-3.

28.Sahni J, Dugel PU, Patel SS, et al. Safety and efficacy of different doses and regimens of faricimab vs ranibizumab in neovascular age-related macular degeneration: the AVENUE phase 2 randomized clinical trial[J]. JAMA Ophthalmol, 2020, 138(9): 955-963. DOI: 10.1001/jamaophthalmol.2020.2685.

29.Khanani AM, Patel SS, Ferrone PJ, et al. Efficacy of every four monthly and quarterly dosing of faricimab vs ranibizumab in neovascular age-related macular degeneration: the STAIRWAY phase 2 randomized clinical trial[J]. JAMA Ophthalmol, 2020, 138(9): 964-972. DOI: 10.1001/jamaophthalmol.2020.2699.

30.Heier JS, Khanani AM, Quezada RC, et al. Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials[J]. Lancet, 2022, 399(10326): 729-740. DOI: 10.1016/S0140-6736(22)00010-1.

31.Leung EH, Oh DJ, Alderson SE, et al. Initial real-world experience with faricimab in treatment-resistant neovascular age-related macular degeneration[J]. Clin Ophthalmol, 2023, 17: 1287-1293. DOI: 10.2147/OPTH.S409822.

32.Bhatwadekar AD, Kansara V, Luo Q, et al. Anti-integrin therapy for retinovascular diseases[J]. Expert Opin Investig Drugs, 2020, 29(9): 935-945. DOI: 10.1080/13543784.2020.1795639.

33.Lima ESR, Mirando AC, Tzeng SY, et al. Anti-angiogenic collagen IV-derived peptide target engagement with α(v)β(3) and α(5)β(1) in ocular neovascularization models[J]. iScience, 2023, 26(2): 106078. DOI: 10.1016/j.isci.2023.106078.

34.Ferro DL, Traverso CE, Nicolò M. The emerging role of the Angiopoietin-Tie pathway as therapeutic target for treating retinal diseases[J]. Expert Opin Ther Targets, 2022, 26(2): 145-154. DOI: 10.1080/14728222.2022.2036121.

35.Gianni-Barrera R, Butschkau A, Uccelli A, et al. PDGF-BB regulates splitting angiogenesis in skeletal muscle by limiting VEGF-induced endothelial proliferation[J]. Angiogenesis, 2018, 21(4): 883-900. DOI: 10.1007/s10456-018-9634-5.

36.La Mendola D, Trincavelli ML, Martini C. Angiogenesis in Disease[J]. Int J Mol Sci, 2022, 23(18): 10962. DOI: 10.3390/ijms231810962.

37.Hussain RM, Ciulla TA. Emerging vascular endothelial growth factor antagonists to treat neovascular age-related macular degeneration[J]. Expert Opin Emerg Drugs, 2017, 22(3): 235-246. DOI: 10.1080/14728214.2017.1362390.

38.Cao J, Zhang F, Xiong W. Discovery of aptamers and the acceleration of the development of targeting research in ophthalmology[J]. Int J Nanomedicine, 2023, 18: 4421-4430. DOI: 10.2147/IJN.S418115.

39.Jaffe GJ, Ciulla TA, Ciardella AP, et al. Dual antagonism of PDGF and VEGF in neovascular age-related macular degeneration: a phase iib, multicenter, randomized controlled trial[J]. Ophthalmology, 2017, 124(2): 224-234. DOI: 10.1016/j.ophtha.2016.10.010.

40.Kato Y, Oguchi Y, Omori T, et al. Complement activation products and cytokines in pachychoroid neovasculopathy and neovascular age-related macular degeneration[J]. Invest Ophthalmol Vis Sci, 2020, 61(13): 39. DOI: 10.1167/iovs.61.13.39.

41.Yang S, Li T, Jia H, et al. Targeting C3b/C4b and VEGF with a bispecific fusion protein optimized for neovascular age-related macular degeneration therapy[J]. Sci Transl Med, 2022, 14(647): j2177. DOI: 10.1126/scitranslmed.abj2177.

42.Jia H, Li T, Sun J, et al. A novel bispecific fusion protein targeting C3b/C4b and VEGF in patients with nAMD: a randomized, open-label, phase 1b study[J]. Am J Ophthalmol, 2023, 248: 8-15. DOI: 10.1016/j.ajo.2022.11.016.

43.Golestaneh N, Chu Y, Xiao YY, et al. Dysfunctional autophagy in RPE, a contributing factor in age-related macular degeneration[J]. Cell Death Dis, 2017, 8(1): e2537. DOI: 10.1038/cddis.2016.453.

44.Nguyen LS, Vautier M, Allenbach Y, et al. Sirolimus and mTOR inhibitors: a review of side effects and specific management in solid organ transplantation[J]. Drug Saf, 2019, 42(7): 813-825. DOI: 10.1007/s40264-019-00810-9.

45.Rowe LW, Minturn RJ, Burgett LA, et al. Intravitreal sirolimus with adjunct aflibercept versus aflibercept monotherapy for persistent, exudative age-related macular degeneration: a pilot study[J]. Int J Retina Vitreous, 2023, 9(1): 1. DOI: 10.1186/s40942-022-00437-6.

46.Rossi E, Bernabeu C. Novel vascular roles of human endoglin in pathophysiology[J]. J Thromb Haemost, 2023, 21(9): 2327-2338. DOI: 10.1016/j.jtha.2023.06.007.

47.Gonzalez VH, Berger B, Goldberg R, et al. Safety and tolerability of intravitreal carotuximab (DE-122) in patients with persistent exudative age-related macular degeneration: a phase I study[J]. Transl Vis Sci Technol, 2021, 10(14): 27. DOI: 10.1167/tvst.10.14.27.

48.Khanani AM, Thomas MJ, Aziz AA, et al. Review of gene therapies for age-related macular degeneration[J]. Eye (Lond), 2022, 36(2): 303-311. DOI: 10.1038/s41433-021-01842-1.

49.Ding K, Shen J, Hafiz Z, et al. AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression[J]. J Clin Invest, 2019, 129(11): 4901-4911. DOI: 10.1172/JCI129085.

50.Tolentino MJ, Tolentino AJ. Investigational drugs in clinical trials for macular degeneration[J]. Expert Opin Investig Drugs, 2022, 31(10): 1067-1085. DOI: 10.1080/13543784.2022.2113375.

51.Khanani AM, Boyer DS, Wykoff CC, et al. Safety and efficacy of ixoberogene soroparvovec in neovascular age-related macular degeneration in the United States (OPTIC): a prospective, two-year, multicentre phase 1 study[J]. EClinicalMedicine, 2024, 67: 102394. DOI: 10.1016/j.eclinm.2023.102394.

52.Blasiak J, Pawlowska E, Ciupińska J, et al. A new generation of gene therapies as the future of wet AMD treatment[J]. Int J Mol Sci, 2024, 25(4): 2386. DOI: 10.3390/ijms25042386.

53.Felfeli T, Juncal VR, Hillier RJ, et al. Aqueous humor cytokines and long-term response to anti-vascular endothelial growth factor therapy in diabetic macular edema[J]. Am J Ophthalmol, 2019, 206: 176-183. DOI: 10.1016/j.ajo.2019.04.002.

Popular papers
Last 6 months