Review on the Safety and Efficacy of Brolucizumab for Neovascular Age-Related Macular Degeneration From Major Studies and Real-World Data

Abstract

Frequent antivascular endothelial growth factor injections in neovascular age-related macular degeneration (nAMD) often lead to poor compliance and suboptimal outcomes. A longer-acting agent has been a pressing unmet need until recently. Brolucizumab, an antivascular endothelial growth factor agent, is a single-chain antibody fragment approved by the US Food and Drug Administration (FDA) on October 8, 2019, for treating nAMD. It delivers more molecules at equivalent volumes of aflibercept, thus achieving a longer-lasting effect. We reviewed literature published in English between January 2016 and October 2022 from MEDLINE, PubMed, Cochrane database, Embase, and Google scholar using the keywords: “Brolucizumab, real-world data, intraocular inflammation (IOI), safety, and efficacy”. Brolucizumab showed reduced injection frequency, better anatomic outcomes, and noninferior vision gains compared with aflibercept in HAWK and HARRIER studies. However, post hoc studies on brolucizumab revealed a higher-than-expected incidence of IOI, leading to the early termination of 3 studies: MERLIN, RAPTOR, and RAVEN for nAMD, branch retinal vein occlusion, and central retinal vein occlusion, respectively. Contrastingly real-world data showed encouraging outcomes in terms of fewer IOI cases. The subsequent amendment of the treatment protocol resulted in reduced IOI. Thereafter US FDA approved its use in diabetic macular edema on June 1, 2022. Based on major studies and real-world data, this review shows that brolucizumab is effective for treating naive and refractory nAMD. The risk of IOI is acceptable and manageable, but proper preinjection screening and high-vigilance care of IOI are needed. More studies are warranted to evaluate further the incidence, best prevention, and treatment measures for IOI.

Comparison of functional and morphologic changes between brolucizumab and faricimab in neovascular age-related macular degeneration

“…Also, a single-chain variable fragment of brolucizumab is a binding agent independent of a heavy molecular support structure, maintaining its total binding capacity to the target. As a result, greater number of molecules per injection can be administered in the same volume, and more bioavailability in target tissues is attained [ 11 ]. This could be responsible for the greater CFT reduction in the IVBr group than in the IVF group throughout the follow-up period.…”

Advances in Diagnosis and Therapy of Retinal Diseases

“…The final article of this APJO issue addresses the safety and efficacy of brolucizumab as intravitreal medication for the therapy of neovascular AMD, as shown in major studies and based upon real-world experiences 8. The intraocular injection of the anti-VEGF agent brolucizumab as a single-chain antibody fragment delivers more molecules at equivalent volumes as compared with aflibercept, resulting in a longer effect with the result of a lower reinjection frequency.…”