Merck announced in a press release the top-line results from the pivotal phase 2b/3 BRUNELLO trial in adults with diabetic macular edema (DME). BRUNELLO is the first of 2 phase 2b/3 trials evaluating the safety and efficacy of remigromig (MK-3000, formerly EYE103), an investigational, potentially first-in-class tetravalent, trispecific antibody designed to activate the Wingless-related integration site pathway, which is involved in the repair and maintenance of the blood-retinal barrier, the company said.
At 52 weeks, both doses of remigromig (0.5 mg and 0.8 mg) independently demonstrated noninferiority 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, vitreous hemorrhage, and treatment discontinuations due to adverse events were observed in the remigromig treatment arms compared with ranibizumab, and further analyses are under way to characterize these findings, the company said in the press release.
The BRUNELLO trial enrolled 984 participants who were randomized 1:1:1 to receive low-dose and high-dose regimens of remigromig or ranibizumab every 4 weeks for the first year. In the second year, the frequency of treatment for participants will shift based on a personalized treatment interval algorithm. The primary endpoint was mean change in BCVA from baseline to week 52 in the study eye of the participants, using standardized Early Treatment of Diabetic Retinopathy Study vision testing.
The BRUNELLO year 1 results will be presented at the American Academy of Ophthalmology (AAO) Annual Meeting in New Orleans on October 10, in the presentation, "BRUNELLO: 1-Year Pivotal Trial Results of Remigromig (MK-3000, formerly EYE103) for the Treatment of Diabetic Macular Edema," by Donald D'Amico, MD. The results will also be discussed with regulatory authorities, Merck said.
According to the company, the BRUNELLO top-line 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 age-related macular degeneration (nAMD), 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 in patients with DME and in a phase 2 proof-of-concept study (SUPER TUSCAN) in patients with nAMD and RVO.
The company said it is also 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 2 pivotal phase 2b/3 trials for the treatment of NVAMD, TORRONTES and MALBEC, and in 2 pivotal phase 3 studies for the treatment of DME, SANGIOVESE, and SYRAH. RP