A Novel Mechanism for Diabetic Macular Edema Treatment
On October 10, 2026, Merck (MSD outside the US and Canada) presented the first one-year results from the pivotal Phase 2b/3 BRUNELLO trial at the American Academy of Ophthalmology (AAO) 2026 Annual Meeting in New Orleans. The study evaluated remigromig (MK-3000, formerly EYE103), an investigational biologic for the treatment of diabetic macular edema (DME).
Remigromig is a potential first-in-class tetravalent, tri-specific antibody designed to activate the Wingless-related integration site (Wnt) pathway. This represents the first new mechanism of action in more than 20 years to demonstrate non-inferior visual acuity compared with standard anti-VEGF therapy in a pivotal DME trial.
Core Results: Non-Inferior Visual Acuity Gains vs. Standard Therapy
In the BRUNELLO study, both remigromig dose arms met the primary endpoint independently, demonstrating non-inferiority in mean change from baseline in best corrected visual acuity (BCVA) at one year compared with monthly 0.5mg ranibizumab.
- Remigromig 0.5 mg arm: Mean BCVA gain of +9.1 letters (95% CI, 8.1-10.1; p=0.0129, multiplicity-adjusted)
- Remigromig 0.8 mg arm: Mean BCVA gain of +8.7 letters (95% CI, 7.7-9.8; p=0.0222, multiplicity-adjusted)
- Ranibizumab arm: Mean BCVA gain of +11.8 letters (95% CI, 10.7-12.8)
Differences between treatment groups were within the prespecified non-inferiority margin and were not considered clinically meaningful. Notably, no secondary endpoints demonstrated superiority to ranibizumab.
Safety Analysis: Proliferative Diabetic Retinopathy Signal to Monitor
While both doses of remigromig were generally well tolerated, adverse events related to proliferative diabetic retinopathy (PDR) occurred more frequently with remigromig than with ranibizumab:
- Remigromig 0.5 mg: 6.7%
- Remigromig 0.8 mg: 6.1%
- Ranibizumab: 0.9%
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% vs 0.9%, respectively). Additional analyses are underway to further characterize these findings.
Researchers noted that PDR rates may reflect natural disease progression in DME patients since 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.
Expert Perspectives: Addressing Unmet Clinical Needs
Dr. Donald J. D'Amico, chair of Ophthalmology at Weill Cornell Medicine, Ophthalmologist-in-Chief at New York-Presbyterian Hospital, and presenting author of the BRUNELLO study, said: "Although anti-VEGF therapies remain the foundation of treatment for diabetic macular edema, up to two thirds of patients fail to achieve clinically meaningful vision gains after one year, underscoring the need to explore new biological pathways. These findings — which demonstrate for the first time that a biologic targeting the Wnt pathway can achieve visual acuity comparable to an established anti-VEGF therapy — support continued evaluation of this novel approach."
Dr. David Guyer, founder, chief executive officer and president of EyeBio, a wholly owned subsidiary of Merck, added: "Despite important advances in care, up to 40% of patients with diabetic macular edema have persistent disease activity after six months of treatment, meaning that they do not respond or only partially respond to therapy. The BRUNELLO study provides important evidence that activating the Wnt pathway, which is involved in the repair and maintenance of the blood-retinal barrier, may offer a potential new way to help patients with DME."
Dr. Dean Y. Li, president of Merck Research Laboratories, stated: "The BRUNELLO results represent an important milestone for people living with diabetic macular edema. As the first new mechanism of action in more than 20 years to demonstrate non-inferior visual acuity compared with standard-of-care anti-VEGF therapy in a pivotal DME study, remigromig has the potential to expand treatment options for retinal specialists and patients."
Ongoing Development Plans
Results from BRUNELLO will be discussed with regulatory authorities. Remigromig is also being evaluated in the ongoing pivotal Phase 2b/3 BAROLO study (NCT06957080) in patients with DME and in a Phase 2 proof-of-concept study (SUPER TUSCAN, NCT07205887) in patients with NVAMD and RVO.
Additionally, Merck is 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 two pivotal Phase 2b/3 trials for NVAMD (TORRONTES and MALBEC) and in two pivotal Phase 3 studies for DME (SANGIOVESE and SYRAH).
About Diabetic Macular Edema
Diabetic macular edema is a leading cause of vision loss among people living with diabetes, impacting nearly 1.6 million people in the U.S. Despite available anti-VEGF therapies as the standard of care, many patients still experience inadequate response or persistent disease activity, highlighting the urgent need for new treatment approaches.
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