Retina Consultants of Texas, Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas.
Ophthalmic Consultants of Boston, Boston, Massachusetts, USA.
Curr Opin Ophthalmol. 2024 Jan 1;35(1):64-72. doi: 10.1097/ICU.0000000000000845. Epub 2023 Oct 10.
Geographic atrophy is an advanced and currently untreatable form of age-related macular degeneration (AMD), which leads to significant compromise of visual function and quality of life. Dysregulation of the complement cascade has been directly implicated in AMD pathogenesis. Pegcetacoplan is a pegylated highly selective bicyclic peptide that inhibits the cleavage of complement component 3 (C3), which represents a key step in propagation of the complement cascade. The phase 2 FILLY trial as well as the phase 3 OAKS and DERBY trials have evaluated the safety and efficacy of pegcetacoplan for the treatment of GA.
The FILLY, OAKS and DERBY trials have demonstrated that local inhibition of C3 cleavage with pegcetacoplan can reduce geographic atrophy lesion growth compared with sham with an effect size of approximately 11-35% depending on the specific trial and specific geographic atrophy phenotype considered. Overall pegcetacoplan has appeared to be well tolerated with the notable side effect of a dose-dependent increase in the rate of exudative AMD development in treated eyes.
The FILLY, OAKS and DERBY trials have demonstrated that pegcetacoplan is a potentially viable treatment for geographic atrophy. Additional data from the 2-year outcomes of DERBY and OAKS as well as data from the ongoing 3-year GALE extension study will provide additional insights into the potential therapeutic benefit of pegcetacoplan. Future studies assessing complement inhibition at earlier stages of AMD, with the goal of preventing geographic atrophy formation, are warranted.
年龄相关性黄斑变性（AMD）的一种晚期且目前尚无治疗方法的形式是地图状萎缩，它会导致视觉功能和生活质量的严重受损。补体级联的失调已被直接牵连到 AMD 的发病机制中。 Pegcetacoplan 是一种聚乙二醇化的高度选择性双环肽，可抑制补体成分 3（C3）的切割，这是补体级联放大的关键步骤。 2 期 FILLY 试验以及 3 期 OAKS 和 DERBY 试验已经评估了 pegcetacoplan 治疗 GA 的安全性和有效性。
FILLY、OAKS 和 DERBY 试验表明，用 pegcetacoplan 局部抑制 C3 切割与假手术相比，可以减少地图状萎缩病变的生长，具体效果大小取决于特定的试验和考虑的特定地图状萎缩表型，约为 11%-35%。总体而言， pegcetacoplan 的耐受性良好，其显著的副作用是治疗眼渗出性 AMD 发展的发生率呈剂量依赖性增加。
FILLY、OAKS 和 DERBY 试验表明， pegcetacoplan 是一种治疗地图状萎缩的潜在可行方法。DERBY 和 OAKS 的 2 年结果以及正在进行的 3 年 GALE 扩展研究的数据将提供更多关于 pegcetacoplan 潜在治疗益处的见解。未来评估 AMD 早期阶段补体抑制的研究，旨在预防地图状萎缩的形成，是必要的。
