Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today announced topline results from the pivotal Phase 2b/3 BRUNELLO trial in adults with diabetic macular edema (DME). BRUNELLO is the first of two Phase 2b/3 trials evaluating the safety and efficacy of remigromig (MK-3000, formerly EYE103), an investigational, potentially first-in-class tetravalent, tri-specific antibody designed to activate the Wingless-related integration site (Wnt) pathway, which is involved in the repair and maintenance of the blood-retinal-barrier.

At 52 weeks, both doses of remigromig (0.5 mg and 0.8 mg) independently demonstrated non-inferiority to active control 0.5 mg ranibizumab for mean change from baseline in best-corrected visual acuity (BCVA) in patients with DME. In addition, both doses of remigromig were generally well tolerated. Higher rates of proliferative diabetic retinopathy (PDR), vitreous hemorrhage, and treatment discontinuations due to adverse events were observed in the remigromig treatment arms compared with ranibizumab. Further analyses are underway to characterize these findings.

The BRUNELLO year one results will be presented at the American Academy of Ophthalmology (AAO) Annual Meeting in New Orleans, Saturday, Oct. 10, at 5:10 p.m. CT [BRUNELLO: 1-Year Pivotal Trial Results of Remigromig (MK-3000, formerly EYE103) for the Treatment of Diabetic Macular Edema; D. D'Amico] and will be discussed with regulatory authorities.

"Despite available therapies, up to 40% of patients with diabetic macular edema do not fully respond and remain at risk of continued vision loss," said Dr. David Guyer, founder, chief executive officer and president, EyeBio, a wholly-owned subsidiary of Merck. "This is the first and only new mechanism of action in 20 years that has achieved Phase 3 results non-inferior to anti-VEGF therapy ‒ representing an important milestone for patients in developing a potential new treatment. We look forward to sharing these findings with the scientific community at AAO."

"We are pleased to share the first Phase 3 findings for remigromig," said Dr. Dean Y. Li, president, Merck Research Laboratories. "We look forward to advancing remigromig in diabetic macular edema, a leading cause of vision loss for people with diabetes, with the hope of offering a new treatment option with the first novel mechanism of action for retinal vascular diseases in more than two decades."

The BRUNELLO topline results build on Merck’s advancing ophthalmology pipeline, which is aimed at promoting retinal recovery by addressing specific retinal diseases associated with vascular leakage and neovascularization, including DME, neovascular (wet) age-related macular degeneration (NVAMD) and macular edema secondary to retinal vein occlusion (RVO). In addition to BRUNELLO, remigromig is 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) in patients with NVAMD and RVO (NCT07205887).

In addition, the company 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 the treatment of NVAMD, TORRONTES (NCT07496567) and MALBEC (NCT07440225), and in two pivotal Phase 3 studies for the treatment of DME, SANGIOVESE (NCT07705555) and SYRAH (NCT07705607).