Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine , Miami , FL , USA.
Department of Ophthalmology, Indiana University School of Medicine , Indianapolis , IN , USA.
Expert Opin Pharmacother. 2019 Oct;20(15):1879-1891. doi: 10.1080/14656566.2019.1636031. Epub 2019 Jul 12.
: Investigational anti-VEGF treatments for neovascular age-related macular degeneration (nAMD) aim to improve visual outcomes and reduce treatment burden; these include long-acting agents, combination strategies, topical agents, sustained-release, and genetic therapies. : The authors provide a comprehensive review of investigational therapies for nAMD, focusing on therapies currently in clinical trial. : Long-acting anti-VEGF agents have demonstrated promising results in phase 3 studies, and include Brolucizumab, a single-chain antibody fragment, and Abicipar, a designed ankyrin repeat protein (DARPin). Other unique anti-VEGF agents in current trials include Conbercept - a fusion protein of the VEGF receptor domains, KSI-301 - an anti-VEGF antibody biopolymer conjugate, and OPT-302 - an inhibitor of VEGF-C/D. Strategies to activate the Tie-2 receptor, some in combination with VEGF inhibition, are of interest, with recent trials of Faricimab, ARP-1536, and nesvacumab. Topical anti-VEGF ± anti-PDGF agents, such as pazopanib, squalamine lactate, regorafenib, and LHA510 have shown limited efficacy and/or have not been advanced, although PAN-90806 continues to advance with promising initial results. Sustained-release anti-VEGF treatments, to address treatment burden, include the ranibizumab Port Delivery System, GB-102, NT-503, hydrogel depot, Durasert, and ENV1305. Similarly, genetic therapies, including RGX-314 and ADVM-022, aim to provide sustained anti-VEGF expression from the retina.
: 用于新生血管性年龄相关性黄斑变性（nAMD）的研究性抗血管内皮生长因子（VEGF）治疗旨在改善视力结果并减轻治疗负担；这些治疗方法包括长效制剂、联合策略、局部制剂、缓释制剂和基因治疗。: 作者全面回顾了 nAMD 的研究性治疗方法，重点介绍了目前正在临床试验中的治疗方法。: 长效抗 VEGF 制剂在 3 期研究中显示出有希望的结果，包括单链抗体片段 Brolucizumab 和设计的锚蛋白重复蛋白（DARPin）Abicipar。目前临床试验中其他独特的抗 VEGF 制剂包括康柏西普- VEGF 受体结构域的融合蛋白、KSI-301-抗 VEGF 抗体生物聚合物缀合物和 OPT-302- VEGF-C/D 抑制剂。激活 Tie-2 受体的策略，一些与 VEGF 抑制联合使用，引起了关注，最近 Faricimab、ARP-1536 和 nesvacumab 的试验就是如此。局部抗 VEGF ± 抗 PDGF 制剂，如帕唑帕尼、硫酸氨聚糖、regorafenib 和 LHA510，显示出有限的疗效和/或未得到进一步发展，尽管 PAN-90806 仍在继续推进，初步结果令人鼓舞。为了减轻治疗负担，缓释抗 VEGF 治疗包括雷珠单抗Port 递送系统、GB-102、NT-503、水凝胶库、Durasert 和 ENV1305。同样，基因治疗，包括 RGX-314 和 ADVM-022，旨在从视网膜提供持续的抗 VEGF 表达。
