Experimental DME therapy matches ranibizumab in pivotal study

Anti-VEGF therapies have transformed treatment of diabetic macular edema (DME), but up to 40% of patients have an incomplete response and remain at risk for vision loss. Remigromig targets the Wnt pathway, representing a novel approach aimed at restoring the blood-retinal barrier rather than solely blocking VEGF.

Merck announced that remigromig (MK-3000), an investigational tri-specific antibody and potential first-in-class Wnt-pathway agonist, met the primary endpoint in the pivotal phase 2b/3 BRUNELLO trial of adults with DME. At 52 weeks, both tested doses (0.5 mg and 0.8 mg) demonstrated noninferiority to ranibizumab for improvement in best-corrected visual acuity, the study's primary endpoint.

The randomized, double-masked trial enrolled 984 participants, comparing remigromig with monthly ranibizumab injections. Both remigromig doses were generally well tolerated; however, higher rates of proliferative diabetic retinopathy, vitreous hemorrhage, and adverse event-related treatment discontinuations were reported in the remigromig arms. Merck said further analyses are underway to better characterize these findings.

The results mark a notable milestone for retinal drug development. According to the company, remigromig is the first therapy with a novel mechanism of action in approximately two decades to achieve phase 3-level efficacy results noninferior to established anti-VEGF treatment in DME.

Detailed 1-year BRUNELLO data will be presented at the American Academy of Ophthalmology Annual Meeting in October 2026 and discussed with regulators. A second pivotal DME study (BAROLO) is ongoing, while remigromig is also being evaluated in neovascular age-related macular degeneration and retinal vein occlusion. Longer-term efficacy, durability, and safety outcomes will help determine whether Wnt-pathway activation can emerge as a new therapeutic class for retinal vascular disease.

Source: Merck. (2026 Sep 24). Merck's Remigromig, a Tri-specific Agonist of the Wnt Pathway, Met Primary Endpoint in the Pivotal Phase 2b/3 BRUNELLO Study of Adults with Diabetic Macular Edema