Merck (NYSE: MRK) reported detailed one-year results from the pivotal Phase IIb/III BRUNELLO trial of remigromig (MK-3000, formerly EYE103), an investigational Wnt-pathway tri-specific antibody, in diabetic macular edema (DME) at the American Academy of Ophthalmology 2026 Annual Meeting. Both doses met the primary non-inferiority endpoint versus monthly ranibizumab, although higher rates of proliferative diabetic retinopathy (PDR) and treatment discontinuations raised safety concerns.
The 984-participant trial evaluated remigromig 0.5 mg and 0.8 mg against ranibizumab 0.5 mg, with all three groups receiving intravitreal injections every four weeks during the first year. At week 52, mean best-corrected visual acuity (BCVA) gains were +9.1 letters (95% CI, 8.1–10.1; p=0.0129) and +8.7 letters (95% CI, 7.7–9.8; p=0.0222) in the respective remigromig arms, versus +11.8 letters (95% CI, 10.7–12.8) with ranibizumab. Both doses independently met the prespecified non-inferiority margin, but neither demonstrated superiority on secondary endpoints.
Adverse events related to PDR, including new-onset cases, occurred in 6.7% and 6.1% of patients receiving remigromig 0.5 mg and 0.8 mg, respectively, compared with 0.9% in the ranibizumab arm. Treatment discontinuations due to adverse events were also higher at 4.9% and 4.5%, versus 0.9%. Merck said PDR cases were generally manageable with standard-of-care treatment and suggested that the findings may partly reflect the drug's mechanism, which targets blood-retinal barrier repair rather than directly suppressing neovascularization. Further safety analyses are underway, and the company plans to discuss the results with regulatory authorities.