Merck’s remigromig met the non-inferiority endpoint versus ranibizumab in the Phase 2b/3 BRUNELLO trial for diabetic macular edema, with safety findings under further review.
Written by: Saniya Katakdhond, PharmD
Reviewed By: Pharmacally Editorial Team
Merck reported topline results from the pivotal Phase 2b/3 BRUNELLO trial evaluating remigromig (MK-3000, formerly EYE103) in adults with diabetic macular edema (DME). Both the 0.5 mg and 0.8 mg doses demonstrated non-inferiority to 0.5 mg ranibizumab for the mean change from baseline in best-corrected visual acuity (BCVA) at 52 weeks.
The investigational intravitreal therapy was generally well tolerated, but the remigromig groups showed higher rates of proliferative diabetic retinopathy (PDR), vitreous hemorrhage, and treatment discontinuations due to adverse events than the ranibizumab group. Merck said further analyses are underway to characterize these findings.
Wnt Pathway Offers a Different Approach to DME
Remigromig is an investigational tetravalent, tri-specific antibody that activates the Wingless-related integration site (Wnt) pathway, which plays a role in repair and maintenance of the blood-retinal barrier.
The mechanism differs from anti-VEGF therapies such as ranibizumab, which target vascular endothelial growth factor to reduce vascular leakage and abnormal blood vessel growth. Merck is evaluating whether Wnt pathway activation can provide an alternative approach to retinal vascular disease.
DME develops when damaged retinal blood vessels leak fluid into the retina, causing swelling in the macula and impairing central vision. Despite advances with existing treatments, some patients experience an incomplete response or remain at risk of continued vision loss.
BRUNELLO Achieves Its Primary Efficacy Objective
The randomized, double-masked BRUNELLO trial (NCT06571045) enrolled 984 adults with DME. Participants were randomized 1:1:1 to receive intravitreal remigromig at 0.5 mg, remigromig at 0.8 mg, or ranibizumab at 0.5 mg.
Treatment was administered every four weeks during the first year. In the second year, treatment frequency will be adjusted according to a personalized treatment interval (PTI) algorithm.
The primary endpoint was the mean change from baseline in BCVA at week 52, assessed using standardized Early Treatment of Diabetic Retinopathy Study (ETDRS) vision testing.
Both remigromig doses independently demonstrated non-inferiority to ranibizumab for the primary endpoint.
The safety profile was generally acceptable, but the higher incidence of PDR, vitreous hemorrhage, and adverse-event-related treatment discontinuations with remigromig warrants further evaluation. Merck has not yet provided detailed numerical data from the topline analysis.
Executive Perspective
Dr. David Guyer, founder, CEO and president of EyeBio, a wholly owned subsidiary of Merck, highlighted the remaining treatment gap in DME. He noted that, despite available therapies, up to 40% of patients may not fully respond and remain at risk of continued vision loss.
Guyer characterized the BRUNELLO findings as the first Phase 3 evidence for a new mechanism in retinal vascular disease in two decades, and said the company expects the data to support further development of remigromig as a potential treatment option.
Dr. Dean Y. Li, president of Merck Research Laboratories, said the company views the BRUNELLO results as the first Phase 3 findings for remigromig and plans to advance the program in DME. He also emphasized the potential significance of evaluating a novel mechanism for retinal vascular diseases, where anti-VEGF therapies remain an established treatment approach.
Development Program Expands Across Retinal Diseases
Remigromig is being evaluated beyond DME. The ongoing BAROLO Phase 2b/3 trial (NCT06957080) is assessing the therapy in DME, while the SUPER TUSCAN Phase 2 study (NCT07205887) is evaluating remigromig in neovascular age-related macular degeneration and retinal vein occlusion.
Merck is also developing MK-8748 (Tiespectus, formerly EYE201), an investigational bispecific antibody that activates the Tie2 pathway while inhibiting VEGF. The program includes the Phase 2b/3 TORRONTES and MALBEC studies in neovascular age-related macular degeneration, along with the Phase 3 SANGIOVESE and SYRAH studies in DME.
AAO Presentation and Regulatory Discussions Ahead
Merck will present the one-year BRUNELLO results at the American Academy of Ophthalmology Annual Meeting in New Orleans on October 10 and plans to discuss the findings with regulatory authorities.
The topline results establish that both remigromig doses met the trial’s primary non-inferiority objective against ranibizumab at 52 weeks. Further characterization of the observed PDR, vitreous hemorrhage, and treatment discontinuation findings will be important as Merck evaluates the therapy’s overall benefit-risk profile and determines its next regulatory steps.
Reference
Merck’s Remigromig, a Tri-specific Agonist of the Wingless-related Integration Site (Wnt) Pathway, Met Primary Endpoint in the Pivotal Phase 2b/3 BRUNELLO Study of Adults with Diabetic Macular Edema, Merck, 24 September 2026
A Study to Evaluate the Efficacy and Safety of 2 Doses of EYE103 Compared with Ranibizumab (0.5 mg) in Participants with DME (BRUNELLO), ClinicalTrials.gov ID NCT06571045
About the Writer
Saniya Sanjay Katakdhond (Linkedin) is a Doctor of Pharmacy professional with hands-on experience in patient case review, clinical documentation, medical record analysis, and patient care.
Her hospital experience has strengthened her understanding of clinical conditions, treatment approaches, and multidisciplinary healthcare practices.
With ICH-GCP certification and a research-oriented approach, she brings clinical insight and attention to detail to healthcare content development.
As a healthcare writer, Saniya focuses on translating clinical knowledge and patient-care experience into clear, accurate, and evidence-informed medical content.