Current drug treatments for both diabetic retinopathy (DR) and diabetic macular edema (DME) are aimed at inhibiting a molecule called vascular endothelial growth factor (VEGF) or employ steroids to broadly treat inflammatory mediators present in DME and DR.
The anti-VEGF medications currently include Avastin, Lucentis and Eylea, while the steroid-based treatments include triamcinolone acetonide, Ozurdex, and Illuvien. Many patients need frequent injections of these drugs, and some experience worsening of their vision or their DR despite treatment with these agents.
Given these limitations, clinical trials are underway to evaluate new therapies that could provide therapeutic effect for a longer duration and/or target other pathways. Here we summarize several such therapies under investigation, primarily focusing on late-stage clinical trials (Phases 2 & 3).
Data from a Phase 3 trial evaluating the medication for wet age-related macular degeneration (AMD) showed more than half of patients were able to continue on a 3-month dosing regimen with Beovu through 1 year.
However, there are safety concerns with this medication due to intraocular inflammation and occlusive retinal vasculitis occurring in some patients receiving the medication for AMD.
The device is surgically implanted into the wall of the eye. The tiny implant can then be refilled in the office with medication as needed. Current studies evaluating patients with wet AMD showed the majority of patients could go 6 months before needing retreatment.
Enrollment for Phase 3 clinical trials evaluating this device for use in patients with DME and DR are ongoing.
The goal of this dual inhibition is to potentially improve outcomes and durability of the treatment. A Phase 2 trial comparing faricimab with Lucentis showed improved visual acuity gains with faricimab as well as improvements in the severity of DR.
Also, this study showed that many patients receiving faricimab could go up to 12 or even 16 weeks before needing retreatment, decreasing frequent treatment burden for these patients. Two Phase 3 clinical trials evaluating faricimab for DME are currently underway.
Early-stage studies of the medication showed that over 70% of patients with DME were able to go more than 4 months without needing retreatment after an initial three loading doses. Larger trials evaluating the drug for use in DME and DR are currently underway.
After the medication is injected, its small particles aggregate or stick together and slowly release over time, allowing for the possibility of an extended treatment effect. Early stage trials showed the medication could last up to 6 months in the majority of patients with wet AMD. The medication is currently in a Phase 2 trial for patients with DME.
Preliminary data from an ongoing Phase 2a trial suggests that combination therapy with Eylea and intravitreal OPT-302 yields superior vision outcomes than treatment with Eylea alone in eyes with DME. Phase 3 trials may be performed in the future.
This approach may provide more consistent and sustained levels of anti-VEGF therapy than can be achieved with repeated injections of medication into the eye with the goal of dramatically reducing treatment burden.
RGX-314 (Regnexbio) is being evaluated for surgical subretinal delivery and in-office suprachoroidal delivery for wet AMD, and a Phase 2 trial for patients DR is also underway. ADVM-022 (Adverum Biotechnologies) is currently evaluating an intravitreal in-office injection to deliver gene therapy for DME in an ongoing Phase 2 trial.
CONCLUSION Although existing anti-VEGF agents are very effective at treating DR and DME in the average patient, some patients continue to lose vision despite therapy, many patients require frequent injections, and some experience worsening of their underlying DR despite adequate treatment with current generation medications.
New drugs that produce a more robust and/or longer-acting anti-VEGF effect or that target new pathways other than VEGF have significant promise in improving the vision and lives of patients with diabetic eye disease.