Merck's Remigromig Hits Primary Endpoint in Pivotal BRUNELLO Trial in Diabetic Macular Edema
核心洞察
Merck (搜索) reported topline results from the pivotal Phase 2b/3 BRUNELLO trial of remigromig (搜索) in adults with diabetic macular edema (搜索), with both doses meeting the primary endpoint.
At 52 weeks, remigromig (搜索) 0.5 mg and 0.8 mg each demonstrated non-inferiority to ranibizumab 0.5 mg for mean change from baseline in best-corrected visual acuity.
Both remigromig (搜索) doses were generally well tolerated, but higher rates of proliferative diabetic retinopathy (搜索), vitreous hemorrhage and adverse event-related discontinuations occurred versus ranibizumab.
Merck (搜索) has announced topline results from the pivotal Phase 2b/3 BRUNELLO trial of remigromig (搜索) (MK-3000, formerly EYE103) in adults with diabetic macular edema (搜索) (DME). At 52 weeks, both the 0.5 mg and 0.8 mg doses of remigromig independently demonstrated non-inferiority to active control 0.5 mg ranibizumab for the primary endpoint of mean change from baseline in best-corrected visual acuity (BCVA).
BRUNELLO is the first of two Phase 2b/3 trials evaluating the safety and efficacy of remigromig (搜索), 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. The drug is administered by intravitreal (IVT) injection.
Safety Findings and Ongoing Analyses
Both doses of remigromig (搜索) were generally well tolerated. However, higher rates of proliferative diabetic retinopathy (搜索) (PDR), vitreous hemorrhage, and treatment discontinuations due to adverse events were observed in the remigromig treatment arms compared with ranibizumab. Merck (搜索) said 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 on Saturday, Oct. 10, at 5:10 p.m. CT, and will be discussed with regulatory authorities.
Trial Design
BRUNELLO is a randomized, double masked pivotal Phase 2b/3 trial (NCT06571045) evaluating two dose levels (0.5 mg and 0.8 mg) of intravitreal remigromig (搜索) versus active control 0.5 mg ranibizumab in adults with DME. The trial enrolled 984 participants who were randomized 1:1:1 to receive low and high dose regimens of remigromig or ranibizumab every four weeks for the first year. In the second year, treatment frequency will shift based on a personalized treatment interval (PTI) algorithm. The primary endpoint is mean change in BCVA from baseline to week 52 in the study eye, using standardized Early Treatment of Diabetic Retinopathy Study (ETDRS) vision testing.
Unmet Need in DME
DME is a serious retinal condition and a leading cause of vision loss for people with diabetes. An estimated 1.6 million people are living with DME in the United States. The condition occurs when damaged blood vessels leak into the retina, resulting in swelling in the macula, the central region of the retina crucial for precise vision necessary for everyday activities. Prevalence is anticipated to rise with the increasing incidence of diabetes.
"Despite available therapies, up to 40% of patients with diabetic macular edema (搜索) do not fully respond and remain at risk of continued vision loss," said Dr. David Guyer, founder, chief executive officer and president of EyeBio (搜索), a wholly-owned subsidiary of Merck (搜索). "This is the first and only new mechanism of action in 20 years that has achieved Phase 3 results non-inferior to anti-VEGF (搜索) 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 (搜索)," said Dr. Dean Y. Li, president, Merck (搜索) Research Laboratories. "We look forward to advancing remigromig in diabetic macular edema (搜索), 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."
Broader Ophthalmology Pipeline
The BRUNELLO results build on Merck (搜索)'s ophthalmology pipeline, which is aimed at promoting retinal recovery by addressing 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 (搜索) (RVO).
Beyond BRUNELLO, remigromig (搜索) 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).
Merck (搜索) is also developing MK-8748 (also known as Tiespectus, EYE201), an investigational bispecific antibody with a dual mechanism that directly activates the Tie2 (搜索) pathway and inhibits VEGF (搜索), with the goal of stabilizing retinal and choroidal blood vessels and reducing fluid accumulation in the macula. MK-8748 is being studied in two pivotal Phase 2b/3 trials for NVAMD, TORRONTES (NCT07496567) and MALBEC (NCT07440225), and in two pivotal Phase 3 studies for DME, SANGIOVESE (NCT07705555) and SYRAH (NCT07705607).