Merck & Co. announced topline results from the pivotal phase 2b/3 BRUNELLO trial evaluating Remigromig (MK-3000, formerly EYE103) in diabetic macular edema (DME).
Let’s start with Remigromig.
The candidate is an investigational, potentially first-in-class tetravalent, tri-specific antibody that is administered via intravitreal (IVT) injection.
How it works: by activating the Wingless-related integration site (Wnt) pathway—involved in the repair and maintenance of the blood-retinal-barrier (BRB)—to increase levels of vascular endothelial growth factor (VEGF) in retinal diseases associated with vascular leakage and neovascularization.
- Note: Remigromig was originally developed by EyeBiotech Limited (EyeBio), which was acquired by Merck as a wholly-owned subsidiary in 2024 as part of its expansion into the ophthalmic industry.
Doesn’t Merck have another ophthalmic candidate in the pipeline?
Indeed. In April we reported that Merck had initiated a pivotal phase 2b/3 trial evaluating MK-8748 (also known as Tiespectus, EYE201) for the treatment of wet age-related macular degeneration (AMD).
Tiespectus is 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.
The candidate is being investigated as follows:
- Wet AMD: Two pivotal phase 2b/3 trials (TORRONTES [NCT07496567] and MALBEC [NCT07440225])
- DME: Two pivotal phase 3 studies (SANGIOVESE [NCT07705555] and SYRAH [NCT07705607])
Where is Remigromig in the clinical development process?
Remigromig is being evaluated for two potential indications:
- DME: Two ongoing registrational phase 2b/3 studies (BAROLO [NCT06957080] and BRUNELLO [NCT06571045])
- Wet AMD: One ongoing phase 2 proof-of-concept study (SUPER TUSCAN [NCT07205887]) investigating the candidate in patients with wet AMD or macular edema following branch retinal vein occlusion (BRVO)
Tell me more about the BRUNELLO trial.
The randomized, double masked pivotal phase 2b/3 study is evaluating the safety and efficacy of two dose levels (0.5 mg and 0.8 mg) of Remigromig versus active control ranibizumab 0.5 mg 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 4 weeks for the first year.
In the second year, the frequency of treatment for participants will shift based on a personalized treatment interval (PTI) algorithm.
What were the main outcome measures?
The primary endpoint: Mean change in best-corrected visual acuity (BCVA) from baseline to week 52, using standardized Early Treatment of Diabetic Retinopathy Study (ETDRS) vision testing.
Secondary outcome measures include:
- Change from baseline in optical coherence tomography (OCT) central subfield thickness (CST) at Week 52
- Time to absence of DME
- Time to gaining ≥15 ETDRS letters
- Change from baseline in focal area zone (FAZ) area on fluorescein angiography (FA) at Week 52
- Proportion of participants:
- With resolution of macular leakage on FA at Week 24
- Without intraretinal and subretinal fluid at the foveal center on OCT at Week 52
- Achieving 20/40 or better BCVA at Week 52
- Number of participants who:
- Experience an ocular and/or systemic adverse event (AE)
- Experience an ocular and/or systemic serious AE (SAE)
- Discontinue study treatment due to an AE
Let’s dive into that topline data.
At 52 weeks, both doses of Remigromig (0.5 mg and 0.8 mg) independently demonstrated non-inferiority to active control ranibizumab 0.5 mg for mean change from baseline in BCVA in DME patients.
- Plus: Both doses of Remigromig were generally well tolerated.
Higher rates of the following were observed in the Remigromig treatment arms compared to ranibizumab:
- Proliferative diabetic retinopathy (PDR)
- Vitreous hemorrhage
- Treatment discontinuations due to AEs
Note: Further analyses are underway to characterize these findings.
Any comments from the company?
“Despite available therapies, up to 40% of patients with diabetic macular edema do not fully respond and remain at risk of continued vision loss,” stated David Guyer, MD, founder, CEO and president, EyeBio.
He added: “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.
When can we expect an update?
Merck will share additional data from the BRUNELLO trial this weekend during the American Academy of Ophthalmology (AAO) annual meeting’s Retina Subspecialty Day.
Details are as follows:
- The session: BRUNELLO: 1-Year Pivotal Trial Results of Remigromig (MK-3000, formerly EYE103) for the Treatment of Diabetic Macular Edema
- The date: Saturday, Oct. 10, at 5:10 pm CST
- The presenter: Donald J. D’Amico, MD