Arshad M. Khanani, MD, MA, FASRS

Hi, I'm Arshad Khanani from CRI Associates. Here at ARVO 2026 I presented the first time results from the phase two Illuvium study looking at efficacy and safety of vamikibart, an anti-IL-6 agent in patients with diabetic macular edema. This is a very important study for the field because this is the first time an anti-IL-6 monotherapy is being compared to anti-VEGF, and I don't think we are going to see a trial like that in the future.

This is a trial that is validating the efficacy of anti-IL-6 in patients with DME. As we know that IL-6 is elevated in patients with diabetic macular edema and plays an important role in inflammation, in the ALLUVIUM study, we looked at 394 patients with center-involving DME and they were randomized to one to one to one to one, to vamikibart 0.25 milligram every eight weeks, vamikibart one milligram every eight weeks, vamikibart one milligram every four weeks or intravitreal ranibizumab 0.5 milligram.

We know that anti- VEGFs work really well in patients with DME. The goal here was to look at the anatomy and the visual gains we are getting with vamikibart. The primary endpoint of this study is an average change in BCVA at weeks 44 to 48 in 259 treatment-naive patients that were enrolled in the study. The baseline characteristics were well balanced looking at BCVA and CST. For the primary endpoint in treatment-naive patients, we saw that vamikibart led to BCVA gains of approximately six letters from baseline across the three doses at the primary endpoint. While patients treated with ranibizumab, 0.5 milligram gain 13 letters. Further looking at the efficacy results, 15 to 23% of treatment-naive patients gained three lines of vision. So that's 15 letters or more of CVA gains from baseline with vamikibart across all dosing groups until the primary endpoint.

Anatomy is important looking at CST and treatment-naive patients. Vamikibart led to improvement of 50 to 70 microns from baseline across all three doses. In addition, looking at resolution of DME, we saw 30 to 40% of treatment-naive patients having CST less than 325 after treatment with vamikibart. Safety is important for a new molecule looking at the safety of vamikibart group and comparing it to ranibizumab. We did see a higher incidence of ocular adverse event, including intraocular inflammation at the higher dose of vamikibart one milligram. To summarize, this is the first time we are comparing anti-IL-6 monotherapy to anti- VEGF. We know that there are 30 to 40% of our patients with DME have suboptimal response to anti-VEGF and this trial validates that targeting IL-6 may help those patients improve vision and anatomy. Thank you very much for your attention.

Roger A. Goldberg, MD

Hi, I'm Roger Goldberg from Bay Area Retina Associates in Walnut Creek, California. And it's great to be here at ARVO 2026 in Denver, where I was thrilled to get to present for the first time the results of the BARDENAS study. This was looking at IL-6 inhibition in conjunction with anti-VEGF for patients with diabetic macular edema. And we compared it monthly, the combination of those two medicines versus ranibizumab at 0.5 milligrams given monthly out for 48 weeks. Patients were either treatment-naive or previously treated. The primary endpoint was actually in the treatment naive population looking at mean change in best corrected visual acuity. And I'll cut to the chase. What we found was that combination therapy with the IL-6 inhibitor vamikibart in conjunction with ranibizumab helped patients gain an additional three to three and a half letters at 48 weeks. We also saw a significant increase in the proportion of patients who had three lines of vision gain.

In anti-VEGF monotherapy, ranibizumab 0.5 given monthly, 30% of patients gained three lines of vision or more. When you combined it with vamikibart, the IL-6 inhibitor, we saw that number increased to 45% of patients achieve three lines of vision gain. That was in the treatment-naive population. In the previously treated and treatment-naive population, all comers in the trial, we saw not only improvements in best corrected visual acuity, again, about a three-letter difference. We also saw an additional 10% of patients achieving three lines of vision gain or more. So really exciting data here to suggest that IL-6 inhibition, given in conjunction with anti-VEGF monotherapy, can help our patients improve more vision. There were in this BARDENAS study, nine cases of intraocular inflammation, including two cases of retinal vasculitis, occlusive retinal vasculitis. And so I think that's really interesting. We do these phase two studies in order to see not just efficacy but also safety.

So as we move forward with the development, there's a clear signal that adding IL-6 inhibition to anti- VEGF therapy helps our patients with DME. And now the question is, can we do this in a different way? And so it's moving forward with a bispecific molecule, so a single molecule that can inhibit both anti- VEGF and IL-6 in one, and that development program is ongoing. Thanks so much.