Brolucizumab Outperforms Aflibercept in DME Regardless of Prior Treatment

Brolucizumab 6 mg has outperformed aflibercept 2 mg in treating diabetic macular edema (DME), regardless of whether patients have been treated with anti-VEGF agents prior, based on a post-hoc analysis of the KINGFISHER trial.1

Although previous research has highlighted the efficacy of anti-VEGFs for DME, the condition’s persistence is still a major cause of concern for patients. Protocol T, a 2-year randomized clinical trial comparing 3 anti-VEGF treatments, spotlighted certain participants who may need frequent dosing to sustain visual and anatomical results. Given this, the phase 3 KINGFISHER study was conducted.1

“This post hoc analysis of the KINGFISHER study was designed and conducted to compare the visual and anatomical outcomes associated with q4w dosing of brolucizumab 6 mg and aflibercept 2 mg in participants with DME in prior anti-VEGF-treated versus treatment-naïve patients,” Michael Ip, MD, department of ophthalmology, David Geffen School of Medicine, UCLA, and colleagues wrote.1

The trial lasted 52 weeks and was double-masked and randomized. To be included, patients were required to have type 1 or type 2 diabetes and a diagnosis of visual impairment due to DME. Treatment-naïve and previously treated patients were included, but anti-VEGF treatment was not permitted in the 3 months prior to baseline. Participants with stroke or myocardial infarction in the last 6 months, other ocular disorders, or uncontrolled glaucoma were excluded.2

A total of 765 patients were screened; of these, 517 were randomly assigned in a 2:1 ratio to either brolucizumab (n = 346) or aflibercept (n = 171). A total of 311 in the brolucizumab arm and 156 in the aflibercept arm completed the study. Investigators observed an improvement in best-corrected visual acuity (BCVA) from baseline in both treatment arms, and the study demonstrated the noninferiority of brolucizumab to aflibercept for BCVA change.2

A higher proportion of participants in the brolucizumab arm also exhibited an improvement in CST compared to aflibercept, and brolucizumab also demonstrated superiority in the absence of intraretinal and subretinal fluid at week 52.2

The post-hoc analysis was based on the full-analysis set, aiming to retrospectively evaluate and compare visual and anatomical outcomes following brolucizumab 6 mg in the treatment-naïve and anti-VEGF treatment subgroups. Investigators assessed change in BCVA from baseline between these subgroups in the brolucizumab arm using Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores.1

Of the 517 randomized patients, 370 (brolucizumab [n = 251]; aflibercept [n = 119]) were treatment-naïve and 147 (brolucizumab [n = 95]; aflibercept [n = 52]) were prior-treated. The mean age in both groups was ~60.5 years. Baseline characteristics were well balanced between the prior treated versus treatment-naïve subgroups, as well as treatment arms between subgroups.1

Investigators noted improvement in mean BCVA across both subgroups and treatment arms. The prior-treated subgroup’s mean BCVA change was numerically higher in the brolucizumab arm (+11 letters) versus the aflibercept arm (+8.6 letters). The treatment-naïve subgroup saw a higher mean BCVA change from baseline (+12.6 letters) in the brolucizumab arm than in the aflibercept arm (+12.2 letters).1

Additionally, anatomical outcomes demonstrated improvement across both subgroups and treatment arms. The prior-treated subgroup saw numerically higher mean change in CSFT in brolucizumab (-255.3 µm) versus aflibercept (-189.6 µm), as did the treatment-naïve subgroup (-231.4 µm in brolucizumab, -199 µm in aflibercept). A higher proportion of patients also had a CSFT <280 µm at week 52 in the brolucizumab arm versus aflibercept, indicative of an absence of DME.1

“Compared with aflibercept 2 mg, brolucizumab 6 mg has an added anatomical advantage, particularly in eyes that have been previously treated with anti-VEGF therapy,” wrote Ip and colleagues. “Additionally, there seems to be a benefit to visual acuity with brolucizumab 6 mg compared with aflibercept 2 mg in eyes that have been previously treated with anti-VEGF therapy.”1

References

1. Ip M, Chaudhary V, He F, et al. Brolucizumab for Diabetic Macular Edema in Participants With/Without Prior Anti-VEGF Exposure: KINGFISHER Study Post Hoc Analysis. Ophthalmol Retina. Published online October 21, 2025. doi:10.1016/j.oret.2025.10.013

2. Singh RP, Barakat MR, Ip MS, et al. Efficacy and Safety of Brolucizumab for Diabetic Macular Edema: The KINGFISHER Randomized Clinical Trial. JAMA Ophthalmol. 2023;141(12):1152-1160. doi:10.1001/jamaophthalmol.2023.5248