New Drug Combo Shows Promise for Better Vision in Diabetic Eye Disease
DENVER – A new treatment approach that targets inflammation in addition to abnormal blood vessel growth may help people with diabetic macular edema (DME) see better and improve the health of their retinas, according to a new clinical trial.
Diabetic macular edema is a complication of diabetes that causes fluid to build up in the macula, the part of the eye responsible for sharp, central vision. Current standard treatment uses drugs called anti-VEGF agents, such as ranibizumab (Lucentis), that block the growth of leaky blood vessels. However, not all patients respond well to this approach.
Researchers are now looking at adding a second type of drug that targets a different pathway – inflammation. The drug vamikibart blocks a protein called interleukin-6 (IL-6), which is known to play a key role in the inflammation that contributes to DME.
In a phase II trial called BARDENAS, scientists compared ranibizumab alone to a combination of ranibizumab plus vamikibart. The study involved 187 patients with type 1 or 2 diabetes and center-involving DME. The main focus was on 124 patients who had not been treated before.
After 44 to 48 weeks, patients who received only ranibizumab improved their best corrected visual acuity (BCVA) by an average of 9.4 letters on an eye chart. Those who got the combination improved by 12.8 letters. The combination group also saw a larger reduction in central subfield thickness (CST), a measure of retinal swelling. CST dropped by an average of 202 micrometers with the combination, compared to 192 micrometers with ranibizumab alone.
More patients in the combination group had large vision gains of 15 letters or more (44.7% vs. 28.6%). More also achieved normal CST levels below 325 micrometers (85.1% vs. 71.4%) and had resolution of macular edema.
However, the combination did come with more side effects. Intraocular inflammation occurred in nine patients in the combination group, and two developed retinal occlusive vasculitis, a serious condition. No such cases happened in the ranibizumab-only group. Elevated eye pressure was also more common in the combination group. Cataract rates were similar between the two groups.
A separate trial called ALLUVIUM tested vamikibart by itself against ranibizumab in 259 previously untreated patients. This study was not designed for a direct head-to-head comparison but to see if the IL-6 inhibitor worked on its own.
Results showed that vamikibart alone improved BCVA by about five to seven letters across three different dose levels, while ranibizumab alone improved it by 13 letters. Between 15% and 23% of vamikibart patients gained 15 or more letters, compared to 40% in the ranibizumab group. Vamikibart also reduced CST by 50 to 70 micrometers, and 33% to 40% of patients had resolution of DME.
Dr. Roger Goldberg of Bay Area Retina Associates in California, who presented the BARDENAS findings at the Association for Research in Vision and Ophthalmology meeting, said the results suggest IL-6 inhibition provides a benefit separate from VEGF blockade. He noted that a phase I trial is already testing a single injection that targets both VEGF and IL-6 at once.
Still, not every patient responded well. During the discussion, an audience member pointed out that many patients in the combination group still did not meet standard response criteria. Goldberg acknowledged that DME is a complex disease with many causes. “I don’t think the IL-6 silver bullet, just targeting that one pathway, is going to be enough for all patients,” he said.
Dr. Arshad Khanani of Sierra Eye Associates in Nevada, who presented the ALLUVIUM data, called the findings a “pivotal moment” for the field. He said doctors now need to figure out which patients might benefit most from anti-inflammatory treatment and whether targeting more than two pathways will be necessary.
Experts agree that inflammation has become a key target in DME treatment. Steroids have been used in the past to fight inflammation but come with well-known safety risks. IL-6 levels are known to be high in the eye fluids of DME patients, and the protein plays a central role in vascular leakage and chronic inflammation.
Vamikibart is a specially designed antibody that is injected directly into the eye. Early studies showed it quickly and effectively suppresses IL-6 in the eye’s aqueous humor.
Goldberg emphasized the need for better tools to personalize care. “What are the biomarkers we can look for to help us better personalize medicine and give patients the exact therapy that they need?” he asked. “I do think we will get there. Having multiple tools in our toolbox is going to be part of the solution.”
Source: MedPage Today
