Brolucizumab noninferior to aflibercept in neovascular age-related macular degeneration

Treatment with brolucizumab 6 mg, dosed every 4 weeks, is not inferior to aflibercept 2 mg, dosed every 4 weeks, in previously treated participants with neovascular age-related macular degeneration (nAMD) and persistent retinal fluid, a study has shown.

“However, incidences of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, also were higher, leading to study termination,” the investigators noted.

This multicentre, randomized, double-masked phase IIIa study assessed the 52-week efficacy and safety of brolucizumab 6 mg administered every 4 weeks compared with aflibercept 2 mg in patients with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent antivascular endothelial growth factor treatment).

The investigators randomly assigned eyes (2:1) to intravitreal brolucizumab 6 mg or aflibercept 2 mg every 4 weeks up to and including week 100. Analysis of noninferiority in mean best-corrected visual acuity (BCVA) change from baseline to week 52 was the primary endpoint. Secondary endpoints included change in central subfield thickness (CST) from baseline to week 52, fluid-free status (no intraretinal fluid and no subretinal fluid), and safety.

At week 52, brolucizumab turned out to be noninferior to aflibercept in BCVA change from baseline (least squares mean difference, ‒0.6 Early Treatment Diabetic Retinopathy Study letters, 95 percent confidence interval [CI], ‒2.1 to 0.9; p<0.001).

Of the participants, 4.8 percent in the brolucizumab group and 1.7 percent in the aflibercept group reported a 15-letter or more BCVA loss from baseline at week 52.

Eyes treated with brolucizumab had significantly reduced CST (p<0.001) compared with those treated with aflibercept. More eyes in the former were also fluid free at week 52 (40.4 percent vs 19.0 percent; 95 percent CI, 13.9‒29.0; p<0.001).

IOI, including retinal vasculitis and retinal vascular occlusion, were 9.3 percent and 4.5 percent for brolucizumab and aflibercept, respectively.