The phase 3a MERLIN study provided critical insights into the efficacy and safety of brolucizumab in patients with neovascular age-related macular degeneration and persistent retinal fluid, despite previous anti-VEGF treatment. The two-year randomized, double-masked trial involved 535 participants who received brolucizumab 6 mg or aflibercept 2 mg every 4 weeks.
In their article, currently published as a pre-proof in Ophthalmology, the researchers noted that in the MERLIN trial visual acuity outcomes with brolucizumab showed noninferiority to aflibercept and anatomical outcomes showed improvement compared with aflibercept. These findings aligned with the HAWK and HARRIER studies, as well as the phase 2 OSPREY trial.
The study found that 4.8% of the eyes in the brolucizumab group had ≥15-letter loss in best-corrected visual acuity (BCVA) from baseline at Week 52 compared with 1.7% of the eyes treated with aflibercept. Additionally, the brolucizumab group eyes had significantly reduced central subfield thickness and a greater proportion were fluid-free at Week 52. However, brolucizumab was associated with a higher rate of intraocular inflammation, including cases of retinal vasculitis (11.5% vs. 6.1% with aflibercept) and retinal vascular occlusion (2.2% vs. 0.6% with aflibercept), which lead to an early termination of the trial at 104 weeks.
At Week 104, change in BCVA was -0.8 letters for brolucizumab and -0.4 letters for aflibercept. However, the investigators did not observe overall improvement in BCVA at termination of the study, perhaps because a greater proportion of eyes treated with brolucizumab lost more letters compared to aflibercept. The “ceiling effect” with previous anti-VEGF treatment likely also contributed to fewer BCVA gains.
Based on the safety data from the MERLIN study along with a review of the previous HAWk and HARRIER studies, the researchers recommended limiting use of brolucizumab to less frequently than q8w following 3 monthly loading doses in eyes with neovascular age-related macular degeneration.
A full list of author disclosures can be found in the published research.
