New Mechanism of DME Treatment Highlights Clinical Trial Updates

Updates to ongoing clinical trials were presented during a session that took place at the American Academy of Ophthalmology 2026 annual meeting. The session included updates on the BRUNELLO trial (NCT05919693), the MEERKAT trial (NCT05642312), and the SANDCAT trial (NCT05642325), among others.

Remigromig Shows Noninferior Visual Outcomes to Anti-VEGF in DME

Updates from the BRUNELLO trial were presented by Donald J. D’Amico, MD, professor and chair of the Israel Englander Department of Ophthalmology at Weill Cornell Medical College and ophthalmologist-in-chief at NewYork-Presbyterian Hospital. The trial primarily focused on remigromig (MK-3000, formerly restoret/EYE103; Merck), which can be used to treat diabetic macular edema (DME). Remigromig is notably not an anti-vascular endothelial growth factor (anti-VEGF) treatment.

“Anti-VEGF therapies for DME have been a remarkable advance but have reached their efficacy ceiling, with many patients having incomplete or impermanent responses at both near and longer time points,” said D’Amico. The search for new therapeutic targets has become a primary goal for the future treatment of DME because of this. Remigromig is a potential treatment option for DME that activates the Wnt pathway to reestablish the blood/retinal barrier.

BRUNELLO is a 2-year trial that aims to test remigromig in patients 18 years and older who are living with type 1 or 2 diabetes with a hemoglobin A_1C of 12% or lower. Participants in the trial also needed an ETDRS letter score between 75 and 24 and a central subfield thickness (CST) of 325 mm or higher. Patients were split 1:1:1 into a remigromig 0.5-0mg group, a remigromig 0.8-mg group, and a ranibizumab 0.5-mg group. All participants received their respective medications every 4 weeks through the first year and then moved to personalized treatment intervals.

The primary end point was the mean change in best-corrected visual acuity (BCVA) from baseline at year 1. Secondary end points included assessing if remigromig was superior to ranibizumab when it came to the change in BCVA and assessing the superiority of remigromig vs ranibizumab in mean change in CST from baseline.

There were 984 participants included in the trial, split into the 3 groups with similar baseline demographics. The primary end point was met for both doses of remigromig vs ranibizumab at year 1. The mean BCVA gain at year 1 was 9.1 letters for remigromig 0.5 mg, 8.7 letters for remigromig 0.8 mg, and 11.8 letters for ranibizumab 0.5 mg. These results were within the noninferiority margin. However, no secondary end point was met, and remigromig was not superior to ranibizumab in either BCVA improvement or CST improvement.

Proliferative diabetic retinopathy (PDR) events were more frequent with remigromig than with ranibizumab (6.7% vs 6.1% vs 0.9% in remigromig 0.5 mg, remigromig 0.8 mg, and ranibizumab, respectively). “PDR cases were manageable. With standard of care, 85% of affected patients gained vision after 1 year,” explained D’Amico. “Being mindful of cross-trial comparisons, the 6.1% to 6.7% PDR rate appears superior to prior sham or grid laser controls in anti-VEGF trials such as RISE and RIDE…and VISTA/VIVID.”

D’Amico concluded that remigromig is the first biologic with a novel mechanism of action that demonstrated a noninferior visual outcome compared with an anti-VEGF for DME. This, he said, could open a promising new pathway to treating DME.

Vamikibart Shows Rapid Improvements in Vision for UME

Ongoing studies testing an alternative method of treating uveitic macular edema (UME) were also presented during the session, by Nisha Acharya, MD, MS, a professor at the University of California, San Francisco, Department of Ophthalmology, who presented findings of the MEERKAT and SANDCAT trials.

Acharya opened by pointing out the unmet need for effective and safe nonsteroid treatment for UME. “UME is a very major problem in patients with uveitis. It’s the major cause of vision loss in patients with uveitis. It is often persistent and doesn’t fully resolve, even when we treat the underlying uveitis,” she explained.

Vamikibart is a first-in-class anti–interleukin-6 (anti-IL-6) monoclonal antibody that can be administered intravitreally. Phase 1 studies showed promising results, leading to the trials testing its performance in patients.

SANDCAT and MEERKAT are identically designed phase 3 trials for patients living with UME. Participants were 18 years or older with UME secondary to noninfectious uveitis. Participants also had a CST of 325mm or higher and a BCVA between 73 and 19 ETDRS letters. Patients were randomized 1:1:1 to vamikibart 1.0 mg, vamikibart 0.25 mg, and a sham dose through 16 weeks, received every 4 weeks. Patients were followed through 52 weeks after the initial dose. The primary end point was the proportion of patients who gained 15 letters or more from baseline.

There were 245 participants in the MEERKAT trial and 256 in the SANDCAT trial. The mean visual acuity at baseline was about 20/60 across groups, and the mean CST was 520 mm. After 16 weeks, the proportions of participants who had a 15-letter gain or higher in the vamikibart 0.25-mg dose (26.1% and 34.0%) and the vamikibart 1.0-mg dose (43.2% and 21.8%) were higher compared with the sham group (6.3% and 13.3%) in both the MEERKAT and SANDCAT trials, respectively, through 16 weeks. However, the vamikibart 1.0-mg group was not significantly better than sham in the SANDCAT group.

These results were consistent through 52 weeks, as the proportion of patients who met the primary end point in the 0.25-mg group were 28.3% in the MEERKAT trial and 23.4% in the SANDCAT trial compared with 6.3% and 12.0% for the sham groups in the respective trials. The 1.0-mg group also saw a significant proportion of patients gain letters from baseline at 21.7% in the MEERKAT trial and 17.3% in the SANDCAT trial.

CST was also improved in those taking both vamikibart doses compared with sham, as those taking the 0.25 mg dose saw an improvement of 187.6 mm and 193.3 mm in the MEERKAT and SANDCAT trials through 16 weeks, respectively, and the 1.0-mg dose group saw improvements of 196.1mm and 209.6mm in the respective trials compared with 57.1mm and 43.3mm in the sham groups. The sham groups also saw a higher proportion of patients needing to be rescued through as needed treatment. Lastly, the safety profile was favorable for vamikibart, with few severe adverse events reported.

“Both of these trials showed rapid improvements in vision and anatomical outcomes, with efficacy being maintained through 52 weeks if you look at the totality of outcomes…. So this appears to be a promising therapy for the treatment of UME,” Acharya concluded.