<p>Brolucizumab: evidence to date in the treatment of neovascular age-related macular degeneration</p>

Abstract

Age-related macular degeneration (AMD) is a global health concern and the leading cause of vision loss in the developed world. Intravitreal anti-vascular endothelial growth factor (VEGF) therapy has revolutionized the treatment of neovascular AMD, but there are still challenges with delivery of care and treatment burden with currently available medications. Brolucizumab is a single-chain antibody fragment inhibitor of all isoforms of VEGF-A. Its small molecular weight allows for high solubility and tissue penetration. Brolucizumab has most recently been evaluated in 2 parallel phase 3 randomized controlled trials which demonstrated its safety and efficacy in an extended dosing regimen. The present review summarizes the safety, visual and anatomic outcomes, and durability of brolucizumab in the treatment of neovascular AMD and discusses some of the extended dosing regimens explored with currently approved medications and other therapies still under clinical investigation.

Inflammatory Complications of Intravitreal Anti-VEGF Injections

“…A seven-year review of 199 endophthalmitis cases by Sachdeva et al found that 8.5% of cases at a tertiary referral academic center followed anti-VEGF injections [ 81 ], while Gupta et al found anti-VEGF injections accounted for 11% of their cases [ 82 ]. Infectious endophthalmitis has been reported with all available anti-VEGF agents, and its frequency does not differ significantly by drug [ 77 , 83 , 84 , 85 ].…”

Cell Surface GRP94 as a Novel Emerging Therapeutic Target for Monoclonal Antibody Cancer Therapy

“…However, despite the clinical use of numerous anticancer therapeutic antibodies, a limited number of their therapeutic targets, including CD20, vascular endothelial growth factor-A (VEGF-A), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), programmed cell death protein-1 (PD-1), and programmed death-ligand 1 (PD-L1), have currently been identified [ 21 , 22 , 23 , 24 , 25 ]. Some examples include ofatumumab, ocrelizumab, ibritumomab tiuxetanand, and rituximab for CD20-targeted mAbs; bevacizumab, ranibizumab, and brolucizumab for VEGF-A-targeted mAbs; cetuximab, panitumumab, and necitumumab for EGFR-targeted mAbs; trastuzumab, and pertuzumab for HER2-targeted mAbs; nivolumab, pembrolizumab, and cemiplimab for PD-1-targeted mAbs; lastly, atezolizumab, avelumab, and durvalumab for PD-L1-targeted mAbs [ 21 , 22 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. As such, identifying novel therapeutic targets and understanding the molecular mechanism of metastatic cancer cells are essential for overcoming unmet medical needs in current cancer therapy.…”

Brolucizumab: A Newly Developed Anti-VEGF Molecule for the Treatment of Neovascular Age-Related Macular Degeneration

“…Two reviews on brolucizumab and the visual, anatomic, and safety outcomes from the key clinical trials were recently published [14, 28, 29]. Here, we summarize the main milestones in the clinical development of brolucizumab, outlining the rationale and role of these key studies, and briefly conclude with the Phase IIIa and b clinical outlook for this agent.…”

“…Aside from anti-VEGFs, other innovative approaches to treatment or delivery, e.g., gene therapy or the development of long-acting drug delivery systems, also hold promise for the management of this disease [8, 14].…”