MERLIN: Two-Year Results of Brolucizumab in Participants with Neovascular Age-Related Macular Degeneration and Persistent Retinal Fluid.

ABSTRACT

PURPOSE: To report the safety and efficacy of brolucizumab (Beovu) 6 mg versus aflibercept (Eylea) 2 mg administered every 4 weeks in participants with neovascular age-related macular degeneration (nAMD) and persistent retinal fluid after the week 52 up to week 104. DESIGN: Multicenter, randomized, double-masked phase 3a study. PARTICIPANTS: Participants with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent anti-VEGF treatment). METHODS: Study eyes were randomized 21 to intravitreal brolucizumab 6 mg or aflibercept 2 mg every 4 weeks for 100 weeks or until study termination. MAIN OUTCOME MEASURES: All available efficacy (analysis of noninferiority in mean best-corrected visual acuity [BCVA], central subfield thickness [CST], fluid-free status [no intraretinal fluid and no subretinal fluid]) and safety data up to study termination, including data up to week 104 for those participants who completed the study before its termination. All P values after week 52 were nominal and reflect observed data for the efficacy analyses. RESULTS: Brolucizumab 6 mg every 4 weeks was noninferior to aflibercept 2 mg in mean BCVA change from baseline to week 104 (least squares mean difference, -0.4 ETDRS letters; 95% confidence interval [CI], -3.7 to 3.0; P = 0.0169). The proportion of eyes with ≥15-letter loss was 6.2% for brolucizumab and 4.7% for aflibercept (P = 0.7762), and a greater proportion of eyes were fluid free at week 104 (52.5% brolucizumab vs. 28.2% aflibercept; 95% CI, 11.9-37.3; P < 0.001) in eyes treated with brolucizumab versus aflibercept. Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, was 11.5% (0.8% and 2.2%) for brolucizumab versus 6.1% (0% and 0.6%) for aflibercept. CONCLUSIONS: Consistent with 52-week results, brolucizumab 6 mg every 4 weeks was noninferior in mean BCVA change, with anatomic outcomes superior to aflibercept 2 mg every 4 weeks from baseline to week 104 or study termination. The incidence of IOI, including retinal vasculitis and retinal vascular occlusion, was higher with brolucizumab versus aflibercept; therefore, brolucizumab should not be used more frequently than every 8 weeks after the loading regimen. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.