DME Drug Remigromig Hits Primary End Point in Phase 3 Trial

Remigromig, a trispecific antibody built to repair a damaged eye barrier rather than block a single growth factor, matched a standard anti–vascular endothelial growth factor (VEGF) therapy on vision outcomes in a large phase 2b/3 trial of diabetic macular edema (DME).¹ The findings would mark the first new mechanism to reach this bar in 2 decades of retinal disease treatment, according to a Merck press release.

“Despite available therapies, up to 40% of patients with diabetic macular edema do not fully respond and remain at risk of continued vision loss,” David Guyer, MD, founder, CEO, and president of EyeBio, a wholly owned subsidiary of Merck, said in a statement. “This is the first and only new mechanism of action in 20 years that has achieved phase 3 results noninferior to anti-VEGF therapy—representing an important milestone for patients in developing a potential new treatment.”

What the BRUNELLO Trial Found

The pivotal BRUNELLO (NCT06571045) trial tested remigromig (MK-3000), an investigational antibody engineered to activate the Wingless-related integration site (Wnt) pathway, a signaling system involved in maintaining the blood-retinal barrier. Merck reported that both doses of remigromig (0.5 mg and 0.8 mg) independently met the trial's primary end point of noninferiority to 0.5-mg ranibizumab (Lucentis; Genentech) for mean change in best-corrected visual acuity from baseline to week 52. The double-masked trial enrolled 984 adults with DME, who were randomized 1:1:1 to low-dose remigromig, high-dose remigromig, or ranibizumab, given every 4 weeks for the first year.

Both remigromig doses were generally well tolerated, but the trial recorded higher rates of proliferative diabetic retinopathy, vitreous hemorrhage, and treatment discontinuation due to adverse events in the remigromig arms than with ranibizumab. Merck said further analyses of those safety signals are underway. Full year 1 results will be presented at the American Academy of Ophthalmology (AAO) annual meeting in New Orleans, Louisiana, October 9-12, 2026. The results will also be discussed with regulators.

Why a Wnt Pathway Approach Matters for DME

Anti-VEGF injections have been the backbone of DME treatment for more than a decade even though up to 40% of patients do not fully respond and remain at risk of continued vision loss. Rather than suppressing VEGF to reduce leakage, remigromig is designed to restore the blood-retinal barrier itself, which could matter for patients who plateau on VEGF suppression alone.

John W. Kitchens, MD, a vitreoretinal surgeon at Retina Associates of Kentucky, told AJMC^® earlier this year that anti-VEGF therapy has reached “its practical ceiling” in DME and that Wnt-pathway approaches aim to restore vascular stability “rather than just fluid suppression.”² Kitchens said a pivotal trial would need to show durability and safety on par with, or better than, established anti-VEGF agents before he would consider adopting a new mechanism.

How Access and Cost Pressures Shape Today's DME Care

Any new treatment would land in a treatment landscape that has been described as uneven. Rahul Khurana, MD, of Northern California Retina Vitreous Associates, said real-world patients with DME receive fewer than half the injections given in clinical trials, and that step-therapy mandates from commercial insurers disproportionately steer bevacizumab (Avastin; Genentech), a lower-cost, off-label option, toward sicker, lower-income patients rather than the more potent agents used in trials.³

“The socioeconomic factors really create a 2-tiered treatment landscape in managing our patients…” Khurana said.

What Comes Next for the DME Pipeline

BRUNELLO is the first of 2 pivotal trials for remigromig in DME. The second trial, BAROLO (NCT06510816), is ongoing, alongside a phase 2 proof-of-concept study testing the drug in wet AMD and retinal vein occlusion.¹ Whether remigromig's noninferiority translates into meaningfully better durability, fewer injections, or benefit for anti-VEGF nonresponders will depend on the fuller data set due at AAO and any subsequent regulatory discussions.

References

1. 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. News release. Merck & Co. September 24, 2026. Accessed September 25, 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/
2. Joszt L. Anti-VEGF has hit its DME ceiling: John Kitchens, MD. AJMC^®. July 27, 2026. Accessed September 25, 2026. https://www.ajmc.com/view/anti-vegf-has-hit-its-dme-ceiling-john-kitchens-md
3. Joszt L. Addressing the real-world gaps in diabetic macular edema care: Rahul Khurana, MD. AJMC. June 8, 2026. Accessed September 25, 2026. https://www.ajmc.com/view/addressing-the-real-world-gaps-in-diabetic-macular-edema-care-rahul-khurana-md