A New Mechanism for DME in the BRUNELLO Trial: Donald J. D’Amico, MD

Remigromig (Merck), an investigational drug that activates the Wingless-related integration (Wnt) signaling pathway, could open “a whole new approach for diabetic macular edema [DME],” according to Donald J. D'Amico, MD, professor and chairman, Weill Cornell Medical Campus; ophthalmologist and chief, New York Presbyterian Hospital, who presented 1-year results from the pivotal BRUNELLO (NCT06571045) trial at the American Academy of Ophthalmology 2026 Annual Meeting.

The noninferiority trial enrolled 984 patients and compared 2 doses of remigromig, 0.5 mg and 0.8 mg, with ranibizumab 0.5 mg, each given by monthly intravitreal injection.

“The results of the trial were really remarkable,” D’Amico said. Both doses were noninferior to anti-VEGF therapy, marking “the first time in over 2 decades that we’ve had a new mechanism of action.”

D’Amico explained that the Wnt pathway “is very important in establishing and maintaining the blood-retinal barrier,” which is disrupted in DME, retinal vein occlusion, and other retinal vascular conditions.

“It is not per se an anti-neovascular agent,” D’Amico noted. The pathway has been difficult to activate because it requires targeting a complicated set of receptors at once, which remigromig achieves.

Merck, which is developing the drug, reported higher rates of proliferative diabetic retinopathy, vitreous hemorrhage, and treatment discontinuations due to adverse events with remigromig than with ranibizumab and said further analyses are underway.¹

Because remigromig matched the standard of care on its own, D’Amico said, the results raise the possibility of combination therapy or intermittent dosing with anti-VEGF agents. “We don’t know any of this yet,” D’Amico cautioned.

BRUNELLO is one part of a larger program that includes BAROLO, a similarly designed trial with a comparable sample size expected to report in the coming months.

“If the results are confirmative, then the sponsor will move forward with registration,” D’Amico said.

Reference

Merck presents one-year results from the pivotal phase 2b/3 BRUNELLO study evaluating remigromig, a tri-specific agonist of the Wingless-related integration site (Wnt) pathway, in adults with diabetic macular edema at AAO 2026. News release. Merck. October 10, 2026. Accessed October 10, 2026. https://www.merck.com/news/mercks-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/