New Orleans, Louisiana, U.S., October 10, 2026
Merck has presented encouraging one-year results from the pivotal Phase 2b/3 BRUNELLO clinical trial evaluating remigromig (MK-3000, formerly EYE103), an investigational antibody therapy for adults with diabetic macular edema (DME). The findings were presented at the American Academy of Ophthalmology (AAO) 2026 Annual Meeting in New Orleans, highlighting a potential new approach to treating a retinal condition that can cause vision loss in people living with diabetes. According to Merck, both evaluated doses of remigromig met the study’s primary endpoint by demonstrating non-inferiority to ranibizumab, an established anti-VEGF treatment, in improving best-corrected visual acuity at one year. The results are significant because remigromig targets the Wingless-related integration site (Wnt) signaling pathway, offering a different biological approach from conventional anti-VEGF therapy. However, the treatment remains investigational and has not been established as an approved alternative for patients with DME.
BRUNELLO Trial Demonstrates Non-Inferior Vision Outcomes
The randomized, double-masked BRUNELLO study enrolled 984 adults with diabetic macular edema and compared two doses of remigromig, administered through intravitreal injection, with ranibizumab 0.5 mg. Participants were assigned to receive remigromig at doses of 0.5 mg or 0.8 mg, or the active-control treatment, with dosing every four weeks during the first year. The primary endpoint measured the mean change from baseline in best-corrected visual acuity (BCVA) at Week 52 using standardized vision testing. At one year, patients receiving remigromig 0.5 mg achieved a mean improvement of 9.1 letters, while those receiving the 0.8 mg dose achieved an improvement of 8.7 letters. Patients receiving ranibizumab recorded a mean improvement of 11.8 letters. Both remigromig dose groups met the predefined non-inferiority criteria, meaning the differences in vision improvement remained within the study’s specified margin. Nevertheless, neither remigromig dose demonstrated superiority over ranibizumab on the reported secondary endpoints. These findings support further investigation of Wnt pathway activation as a potential therapeutic strategy, while emphasizing that comparable vision outcomes do not establish superiority or prove an overall clinical advantage.
Safety Findings and Clinical Considerations
Merck reported that both remigromig doses were generally well tolerated, although certain safety findings require careful evaluation. Proliferative diabetic retinopathy (PDR), a complication involving abnormal blood vessel growth in the retina, occurred more frequently in the remigromig groups than in the ranibizumab group. Reported PDR rates were 6.7% with remigromig 0.5 mg, 6.1% with remigromig 0.8 mg, and 0.9% with ranibizumab. Treatment discontinuations due to adverse events were also more frequent with remigromig, occurring in 4.9% of patients receiving the lower dose and 4.5% receiving the higher dose, compared with 0.9% for ranibizumab. Merck stated that additional analyses are underway to better characterize these findings. The company also noted that reported PDR cases were generally manageable with standard-of-care treatment. Further safety assessment will be important as researchers evaluate the therapy’s overall benefit-risk profile and its potential role in retinal disease management.
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Wnt Pathway Offers a New Therapeutic Approach
Remigromig is an investigational tetravalent, tri-specific antibody designed to activate the Wnt signaling pathway, which plays a role in repairing and maintaining the blood-retinal barrier. Damage to this barrier can allow fluid to leak into the retina, contributing to macular swelling and impaired central vision in people with DME. Unlike anti-VEGF medicines, which target vascular endothelial growth factor to reduce abnormal blood vessel activity and leakage, remigromig is being developed to address retinal barrier repair through a different biological mechanism. Merck believes this approach could expand future treatment options for patients who experience persistent disease despite currently available therapies. The company estimates that approximately 1.6 million people in the United States live with DME, and some patients continue to experience disease activity despite treatment. Remigromig is also being studied in other retinal conditions, including neovascular age-related macular degeneration and macular edema associated with retinal vein occlusion.
Next Steps for Merck’s Ophthalmology Pipeline
Following the BRUNELLO findings, Merck plans to discuss the results with regulatory authorities. The company is also evaluating remigromig in the ongoing pivotal Phase 2b/3 BAROLO study in adults with DME, while the Phase 2 SUPER TUSCAN study is investigating the treatment in neovascular age-related macular degeneration and retinal vein occlusion. The second year of BRUNELLO includes a planned shift to personalized treatment intervals, allowing investigators to assess treatment performance under an adjusted dosing approach. Future data will help clarify the durability of visual improvements, the safety profile, and the potential clinical value of Wnt pathway activation. The one-year results represent an important research milestone, but further evidence and regulatory review are needed before remigromig can be considered an established treatment option.
Source: Merck press release
