Semeraro F, Morescalchi F, Duse S, Parmeggiani F, Gambicorti E, Costagliola C
Department of Medical and Surgical Specialties, Radiological Specialties and Public Health, Ophthalmology Clinic, University of Brescia, Piazzale Spedali Civili 1, Brescia, Italy.
Drug Des Devel Ther. 2013 Aug 5;7:711-22. doi: 10.2147/DDDT.S40215. eCollection 2013.
Vascular endothelial growth factor (VEGF) is a naturally occurring glycoprotein in the body that acts as a growth factor for endothelial cells. It regulates angiogenesis, enhances vascular permeability, and plays a major role in wet age-related macular degeneration. The consistent association between choroidal neovascularization and increased VEGF expression provides a strong reason for exploring the therapeutic potential of anti-VEGF agents in the treatment of this disorder. Blockade of VEGF activity is currently the most effective strategy for arresting choroidal angiogenesis and reducing vascular permeability, which is frequently the main cause of visual acuity deterioration. In recent years, a number of other molecules have been developed to increase the efficacy and to prolong the durability of the anti-VEGF effect. Aflibercept (EYLEA®; Regeneron Pharmaceutical Inc and Bayer), also named VEGF Trap-eye, is the most recent member of the anti-VEGF armamentarium that was approved by the US Food and Drug Administration in November 2011. Because of its high binding affinity and long duration of action, this drug is considered to be a promising clinically proven anti-VEGF agent for the treatment of wet maculopathy.
This article reviews the current literature and clinical trial data regarding the efficacy and the pharmacological properties of VEGF-Trap eye and describes the possible advantages of its use over the currently used "older" anti-VEGF drugs.
For this review, a search of PubMed from January 1989 to May 2013 was performed using the following terms (or combination of terms): vascular endothelial growth factors, VEGF, age-related macular degeneration, VEGF-Trap eye in wet AMD, VEGF-Trap eye in diabetic retinopathy, VEGF-Trap eye in retinal vein occlusions, aflibercept. Studies were limited to those published in English.
Two Phase III clinical trials, VEGF Trap-eye Investigation of Efficacy and Safety in Wet AMD (VIEW) 1 and 2, comparing VEGF Trap-eye to ranibizumab demonstrated the noninferiority of this novel compound. The clinical equivalence of this compound against ranibizumab is maintained even when the injections are administered at 8-week intervals, which indicates the potential to reduce the risk of monthly intravitreal injections and the burden of monthly monitoring.
血管内皮生长因子(VEGF)是体内一种天然存在的糖蛋白,可作为内皮细胞的生长因子。它调节血管生成,增强血管通透性,并在湿性年龄相关性黄斑变性中起主要作用。脉络膜新生血管形成与VEGF表达增加之间的持续关联为探索抗VEGF药物在治疗该疾病中的治疗潜力提供了有力理由。阻断VEGF活性是目前阻止脉络膜血管生成和降低血管通透性的最有效策略,而血管通透性降低通常是视力下降的主要原因。近年来,已开发出许多其他分子以提高抗VEGF效应的疗效并延长其持续时间。阿柏西普(EYLEA®;再生元制药公司和拜耳公司),也称为VEGF Trap-eye,是2011年11月获得美国食品药品监督管理局批准的抗VEGF药物库中的最新成员。由于其高结合亲和力和长效作用,该药物被认为是一种有前途的经临床验证的抗VEGF药物,可用于治疗湿性黄斑病变。
本文回顾了有关VEGF Trap-eye的疗效和药理特性的当前文献和临床试验数据,并描述了其相对于目前使用的“旧”抗VEGF药物使用的可能优势。
为进行本综述,使用以下术语(或术语组合)对1989年1月至2013年5月的PubMed进行了检索:血管内皮生长因子、VEGF、年龄相关性黄斑变性、湿性年龄相关性黄斑变性中的VEGF Trap-eye、糖尿病性视网膜病变中的VEGF Trap-eye、视网膜静脉阻塞中的VEGF Trap-eye、阿柏西普。研究限于以英文发表的研究。
两项III期临床试验,即湿性年龄相关性黄斑变性中VEGF Trap-eye疗效和安全性研究(VIEW)1和2,将VEGF Trap-eye与雷珠单抗进行比较,证明了这种新型化合物的非劣效性。即使每8周注射一次,该化合物与雷珠单抗的临床等效性仍然保持,这表明有可能降低每月玻璃体内注射的风险和每月监测的负担。