Improving or maintaining visual acuity is the main goal for the treatment of neovascular age-related macular degeneration (nAMD). Current nAMD standard of care dictates frequent intravitreal (IVT) anti–vascular endothelial growth factor (VEGF) injections, which places a substantial burden on patients, caregivers, and physicians. Brolucizumab, a newly developed anti-VEGF molecule for nAMD treatment, has demonstrated longer durability and improvement in visual and anatomic outcomes in clinical studies in a q12-week regimen, indicating its potential to reduce treatment burden as an important therapeutic tool in nAMD management. This review focuses on the development of brolucizumab and the preclinical and clinical studies evaluating its efficacy, tolerability, and safety. Brolucizumab (also known as “RTH258” and “ESBA1008”) is a humanized, single-chain variable fragment (scFv) antibody with a molecular mass of approximately 26 kDa that inhibits VEGF-A. Preclinical studies show that brolucizumab readily penetrates the retina to reach the retinal pigment epithelium (RPE)/choroid with minimal subsequent systemic exposure. The safety, tolerability, and efficacy of a single IVT brolucizumab administration in patients with treatment-naïve nAMD were first demonstrated in the SEE Phase 1/2 study. The OSPREY Phase 2 study showed brolucizumab to be as efficacious as aflibercept in a q8-week regimen with regard to best-corrected visual acuity (BCVA) and brolucizumab achieving greater fluid resolution. Brolucizumab-treated patients in the OSPREY study were subsequently challenged with a q12-week dosing interval, and the outcomes provided key information for the study design and end points of the Phase 3 studies. In the HAWK and HARRIER Phase 3 studies, after 3 monthly loading injections, brolucizumab treatment regimen (q12-week or q8-week) was guided by individual disease activity assessment using functional and anatomic parameters (central subfield thickness [CST], intraretinal fluid [IRF], or subretinal fluid [SRF]) versus aflibercept (q8-week). Fewer brolucizumab 6-mg treated eyes had disease activity versus aflibercept, and anatomic outcome results at weeks 16 and 48 demonstrate brolucizumab as a potent drying agent. Moreover, of patients treated with 6 mg brolucizumab, 55.6% and 51.0% maintained a q12-week dosing interval immediately after the loading phase until week 48 in HAWK and HARRIER, respectively. These Phase 3 studies demonstrated that the brolucizumab q12-week regimen maintains efficacy and safety while reducing treatment burden associated with regular IVT injections for patients with nAMD.

改善或保持视敏度是治疗新血管性年龄相关性黄斑变性（nAMD）的主要目标。当前的nAMD护理标准要求频繁注射玻璃体内（IVT）抗血管内皮生长因子（VEGF），这给患者，护理人员和医生带来了沉重负担。Brolucizumab是一种新开发的用于nAMD治疗的抗VEGF分子，在q12周方案中的临床研究中已显示出更长的耐久性以及视觉和解剖学结果的改善，表明其有可能减轻作为nAMD管理中重要治疗工具的治疗负担。这篇综述着重于溴珠单抗的开发以及评估其疗效，耐受性和安全性的临床前和临床研究。Brolucizumab（也称为“ RTH258”和“ ESBA1008”）是人源化的，分子量约为26 kDa的单链可变片段（scFv）抗体，可抑制VEGF-A。临床前研究表明，brolucizumab易于穿透视网膜，到达视网膜色素上皮（RPE）/脉络膜，而随后的全身暴露最少。SEE 1/2期研究首次证明了单次IVT布洛珠单抗对未接受过治疗的nAMD患者的安全性，耐受性和疗效。OSPREY 2期研究显示，在最佳矫正视敏度（BCVA）和可实现更大流体分辨率的溴珠单抗方面，在第8周的治疗方案中，溴珠单抗与aflibercept一样有效。随后在OSPREY研究中接受布洛珠单抗治疗的患者接受了每12周一次的给药间隔挑战，结果为研究设计和第三阶段研究的终点提供了关键信息。在HAWK和HARRIER 3期研究中，每月3次负荷注射后，使用功能和解剖学参数（中央亚视野厚度[CST]，视网膜内液[ IRF]或视网膜下液[SRF]）与aflibercept（第8周）。接受6mg溴珠单抗治疗的眼睛与aflibercept相比具有疾病活性，并且在第16周和第48周的解剖结果表明，溴珠单抗是一种有效的干燥剂。此外，在接受6 mg溴珠单抗治疗的患者中，分别在负荷阶段之后至HAWK和HARRIER的第48周，分别维持q12周的给药间隔至12周。