MERLIN: Brolucizumab not inferior to aflibercept in nAMD

Two-year treatment with brolucizumab 6 mg every 4 weeks demonstrates noninferiority in mean best-corrected visual acuity (BCVA), with superior anatomic outcomes, to aflibercept 2 mg every 4 weeks in patients with neovascular age-related macular degeneration (nAMD), as shown in the MERLIN study.

However, the incidence of intraocular inflammation (IOI), such as retinal vasculitis and retinal vascular occlusion, is greater with brolucizumab than with aflibercept.

"[T]herefore, brolucizumab should not be used more frequently than every 8 weeks after the loading regimen,” the researchers said.

Brolucizumab 6 mg every 4 weeks was noninferior to aflibercept 2 mg in terms of mean BCVA change from baseline to week 104 (least squares mean difference, –0.4 ETDRS letters, 95 percent confidence interval [CI], –3.7 to 3.0; p=0.0169). [Ophthalmology 2025;132:131-140]

The proportion of eyes with ≥15-letter loss was higher in the brolucizumab arm than the aflibercept arm (6.2 percent vs 4.7 percent; p=0.7762). Additionally, significantly more eyes treated with brolucizumab were fluid free at week 104 relative to those treated with aflibercept (52.5 percent vs 28.2 percent, 95 percent CI, 11.9–37.3; p<0.001).

Notably, IOI, including retinal vasculitis and retinal vascular occlusion, occurred more frequently in eyes treated with brolucizumab versus aflibercept (11.5 percent vs 6.1 percent).

“After careful evaluation of the individual benefit-risk for a given patient, it is recommended that brolucizumab should not be used more than frequently than every 8 weeks after the loading regimen,” according to the researchers.

Consistent results

The anatomic benefits derived from brolucizumab in MERLIN are similar to those seen in other clinical studies of brolucizumab that examined treatment-naive eyes with nAMD (ie, OSPREY, HAWK, and HARRIER) and eyes receiving a treat-and-extend paradigm (ie, TALON). [Ophthalmology 2017;124:1296-1304; Ophthalmology 2020;127:72-84]

In addition, a post hoc analysis of the HAWK and HARRIER studies revealed that brolucizumab every 8 or 12 weeks resolved the fluid and reduced the central subfield thickness (CST) more effectively than aflibercept. [Ophthalmol Retina 2022;6:377-386]

“Taken together, the anatomic benefits of brolucizumab, when dosed no fewer than every 8 weeks after the 3 loading doses, could represent a treatment option in patients with nAMD with persistent fluid despite previous regular treatments with other anti-VEGF agents,” the researchers said. 

Study details

MERLIN is a multicentre, randomized, double-masked phase IIIa study that included participants with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent anti-VEGF treatment). Study eyes were randomly assigned in a 2:1 ratio to treatment with either intravitreal brolucizumab 6 mg or aflibercept 2 mg every 4 weeks for 100 weeks or until study termination.

Researchers assessed all available efficacy (analysis of noninferiority in mean BCVA, CST, fluid-free status) and safety data up to study termination, including data up to week 104 for participants who completed the study prior to its termination. All p-values after week 52 were nominal and reflected observed data for the efficacy analyses.