IRCCS-Fondazione Bietti, Rome, Via Livenza, 3, 00198, Rome, Italy.
Unit of Clinical Pharmacology, A.O.U. "G. Martino", Messina, Italy.
BioDrugs. 2021 Nov;35(6):673-692. doi: 10.1007/s40259-021-00499-2. Epub 2021 Oct 16.
Age-related macular degeneration (AMD) is a leading cause of visual impairment and blindness in older adults. The prognosis for the neovascular type of advanced AMD improved with the introduction of biological drugs with antiangiogenic properties, beginning with off-label bevacizumab, which was first used intravitreally in 2006. These drugs target newly formed vessels that grow beneath the center of the retina, causing loss of central vision, and they can help to maintain or improve vision. Repeated intravitreal injections are needed to achieve prolonged inhibition of proangiogenic cytokines, primarily vascular endothelial growth factor (VEGF). Major regulatory agencies have approved several molecules for AMD treatment, including ranibizumab, aflibercept, and brolucizumab. The development of further drugs was mainly targeted at prolonging anti-VEGF inhibition-thus reducing the frequency of injections-and expanding the biological targets of proangiogenic cytokine inhibition. Finally, biosimilars are already being marketed in some countries, allowing the containment of costs of AMD treatment, which are growing steadily in many settings because of the need for long-term treatment. This review summarizes the properties and clinical profiles of anti-VEGF biological drugs that are approved to treat neovascular AMD as well as ongoing research on molecules that may be marketed in the near future.
年龄相关性黄斑变性(AMD)是导致老年人视力损害和失明的主要原因。新型血管生成型晚期 AMD 的预后因具有抗血管生成特性的生物药物的问世而得到改善,其中最早于 2006 年开始在眼内使用的贝伐单抗(bevacizumab)即为开处方外用药。这些药物靶向在视网膜中心下方生长的新形成的血管,导致中心视力丧失,可帮助维持或改善视力。为了实现对促血管生成细胞因子(主要是血管内皮生长因子 [VEGF])的长期抑制,需要反复进行眼内注射。主要监管机构已批准了几种用于 AMD 治疗的药物,包括雷珠单抗(ranibizumab)、阿柏西普(aflibercept)和康柏西普(brolucizumab)。进一步药物的研发主要针对延长抗-VEGF 抑制作用,从而减少注射频率,并扩大促血管生成细胞因子抑制的生物靶标。最终,生物类似药已在一些国家上市,这使得 AMD 治疗的成本得以控制,因为在许多情况下,由于需要长期治疗,治疗成本在不断增加。本文总结了已批准用于治疗新生血管性 AMD 的抗 VEGF 生物药物的特性和临床概况,以及可能在不久的将来上市的药物的研究进展。