Molecular structure, pharmacokinetics and clinical evidence of brolucizumab: a narrative review

Abstract

Macular neovascularization (MNV) is the hallmark of neovascular age-related macular degeneration (nAMD), one of the leading causes of vision loss in the developed world. The current MNV standard of care including frequent intravitreal anti-vascular endothelial growth factor (VEGF) injections, although has revolutionized favorably the treatment, places a substantial burden on patients, caregivers, and physicians. Brolucizumab is a newly developed single-chain antibody fragment that inhibits activation of VEGF receptor 2 with in vitro affinity and potency comparable to commercially-available anti-VEGF agents. Its small molecular weight and its design allow for high solubility and retinal tissue penetration, and improve binding affinity to the target. Also a high clearance rate leading to minimal systemic exposure was observed. Brolucizumab has shown similar gains in visual acuity compared with other anti-VEGF molecules but a higher and earlier resolution of nAMD related fluid, achieving sustained macular dryness with longer mantainance injection interval ranging from 8 to 12 weeks after monthly loading doses. Rare cases of ocular inflammation also including retinal vasculitis and retinal vascular occlusions referred to an immune-mediated reaction posed safety concerns on selected patients and mantainance treatment interval shorter than 8 weeks. The present review summarizes several key points including the molecular structure and pharmacokinetics, the preclinical and clinical evidence of brolucizumab administration evaluating its efficacy, tolerability, and safety, extended dosing regimens and other indications still under clinical investigation.