Merck announced the first presentation of 1-year results from the pivotal phase 2b/3 BRUNELLO trial evaluating remigromig (MK-3000, formerly EYE103), an investigational, potentially first-in-class tetravalent, trispecific antibody designed to activate the Wingless-related integration site (Wnt) pathway, for the treatment of diabetic macular edema (DME). Results were presented at the American Academy of Ophthalmology 2026 annual meeting in New Orleans.

In the BRUNELLO study, both remigromig dose arms met the primary endpoint independently, demonstrating noninferiority in mean change from baseline in best corrected visual acuity (BCVA) at 1 year compared with monthly 0.5 mg ranibizumab. Mean BCVA gains at year 1 were +9.1 letters (95% CI, 8.1-10.1; P=.0129, multiplicity-adjusted) with remigromig 0.5 mg and +8.7 letters (95% CI, 7.7-9.8; P=.0222, multiplicity-adjusted) with remigromig 0.8 mg, compared with +11.8 letters with ranibizumab (95% CI, 10.7-12.8). Differences between treatment groups were within the prespecified noninferiority margin and were not considered clinically meaningful. No secondary endpoints demonstrated superiority to ranibizumab, the company said. 

Although both doses of remigromig were generally well tolerated, adverse events related to proliferative diabetic retinopathy (PDR) occurred more frequently with remigromig than with ranibizumab (6.7% and 6.1% with remigromig 0.5 mg and 0.8 mg, respectively, vs 0.9%), inclusive of new-onset PDR.¹ In addition, higher rates of treatment discontinuations due to adverse events were observed in the remigromig treatment arms compared with ranibizumab (4.9% and 4.5% with remigromig 0.5 mg and 0.8 mg, respectively, vs 0.9%). Additional analyses are underway to further characterize these findings. PDR rates may reflect natural disease progression in DME patients because remigromig focuses on repair and maintenance of the blood-retinal barrier rather than directly suppressing new vessel growth. PDR cases were generally manageable with standard-of-care treatment.

The BRUNELLO trial data further strengthens Merck’s advancing ophthalmology pipeline, which is aimed at promoting retinal recovery by addressing specific retinal diseases associated with vascular leakage and neovascularization, including DME, neovascular (wet) age-related macular degeneration (NVAMD) and macular edema secondary to retinal vein occlusion (RVO).

Results from BRUNELLO will be discussed with regulatory authorities. Remigromig is also being evaluated in the ongoing pivotal Phase 2b/3 BAROLO study in patients with DME and in a phase 2 proof-of-concept study (SUPER TUSCAN) in patients with NVAMD and RVO.

The company is also developing MK-8748 (also known as Tiespectus, EYE201), a novel investigational bispecific antibody with a dual mechanism that directly activates the Tie2 pathway and inhibits VEGF with the goal of stabilizing retinal and choroidal blood vessels and reducing fluid accumulation in the macula. MK-8748 is currently being studied in 2 pivotal phase 2b/3 trials for the treatment of NVAMD, TORRONTES and MALBEC, and in 2 pivotal phase 3 studies for the treatment of DME, SANGIOVESE and SYRAH.