Université de Paris, Ophthalmology Department, AP-HP, Hôpital Lariboisière, Paris, France.
Hospital General de Catalunya, Barcelona, Spain.
Ophthalmologica. 2021;244(2):93-101. doi: 10.1159/000513048. Epub 2020 Nov 16.
Despite the success of anti-vascular endothelial growth factors (anti-VEGFs), currently, there is a need for highly effective compounds that can alleviate the burden of managing neovascular age-related macular degeneration (nAMD).
To review the milestones in the molecular and clinical development of brolucizumab, the first single-chain antibody fragment (scFv) designed specifically for intraocular use in humans.
In this article, we summarize the preclinical and current clinical evidence of brolucizumab administration with an overview of the other treatment regimens and additional indications under investigation.
The unique molecular design of brolucizumab led to a low molecular weight of only 26 kDa, allowing for a concentrated molar dose of 1 intravitreal injection compared with other anti-VEGF agents. Phase I and II clinical trial outcomes validated the efficacy of brolucizumab in the treatment of nAMD with signals of a more durable treatment effect. The pivotal phase III trials, HAWK and HARRIER, which included a total of 1,817 patients, established that brolucizumab can be administered every 3 months while maintaining disease control.
The preclinical and clinical data on brolucizumab provide evidence of sustained disease control with longer injection intervals, thus potentially reducing the treatment burden in patients with nAMD.
尽管抗血管内皮生长因子（anti-VEGF）治疗取得了成功，但目前仍需要高效的化合物来减轻新生血管性年龄相关性黄斑变性（nAMD）的治疗负担。
回顾专门为人类眼内使用而设计的首个单链抗体片段（scFv）——brolucizumab 的分子和临床开发历程中的重要里程碑。
本文总结了 brolucizumab 的临床前和临床证据，概述了其他治疗方案和正在研究的其他适应证。
brolucizumab 的独特分子设计导致其分子量仅为 26 kDa，与其他抗 VEGF 药物相比，每支玻璃体内注射的浓缩摩尔剂量为 1。I 期和 II 期临床试验结果证实了 brolucizumab 治疗 nAMD 的疗效，具有更持久的治疗效果信号。共纳入 1817 例患者的两项关键性 III 期试验 HAWK 和 HARRIER 表明，brolucizumab 每 3 个月给药 1 次即可维持疾病控制。
brolucizumab 的临床前和临床数据提供了更长的注射间隔仍能持续控制疾病的证据，从而可能减轻 nAMD 患者的治疗负担。
