In a late breaking session, a one-time gene therapy was found in a phase 2 trial to provide sustained release of dexamethasone in patients with diabetic macular edema and retinal vein occlusion. The trial is ongoing.
A one-time gene therapy enables the sustained release of dexamethasone in patients with diabetic macular edema and retinal vein occlusion. Late-breaking research of ABBV-RGX-314 was presented at the annual meeting of the American Academy of Ophthalmology.
Retinal vein occlusion (RVO) is the second most common cause of vision loss due to retinal vascular diseases. Macular edema is swelling in part of the retina and can result in blurry vision. A common cause of edema is diabetic retinopathy, an eye condition that causes vision loss in people with diabetes. Macular edema due to RVO is typically treated with repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) therapies, but these require repeated injections.
Six-month data from the phase 2 ALTITUDE were presented by Sumit Sharma, M.D., assistant professor of ophthalmology at Cole Eye Institute at the Cleveland Clinic. The ALTITUDE trial is a dose-escalation study of about 100 patients with diabetic retinopathy without center-involved diabetic macular edema. ABBV-RGX-314 is administered to the suprachoroidal space (space in the back of the eye) in a single injection.
ABBV-RGX-314 is being developed by RegenXBio and partner AbbVie and contains a gene encoding for a monoclonal antibody fragment. The expressed protein is designed to neutralize VEGF and modify the pathway for the formation of new blood vessels. It uses an adeno-associated viral (AAV) vector for gene transfer.
At month six in all cohorts, study investigators found that the gene therapy reduced central subfield thickness (CST) and improved or led to stable best-corrected visual acuity (BCVA). In the trial, 70.8% of patients achieved Diabetic Retinopathy Severity Scale improvement vs. 25.0% of those in the control group. ABBV-RGX-314 reduced vision-threatening events by 89% compared with the control group, and no patients who received the therapy worsened more than two steps compared with control.
The study also found that dose level 2 prevented disease progression and reduced vision-threatening events in nonproliferative diabetic retinopathy patients at one year.
The safety is comparable to other intravitreal steroids. As of Sept. 25, 2023, ABBV-RGX-314 was reported to be well tolerated at dose levels 1 and 2. Seven serious adverse events were reported, none of which were considered drug related. For the 50 patients in dose levels 1 and 2, common ocular treatment-emergent adverse events in the study eye through one year included conjunctival hemorrhage and conjunctival hyperemia.
Three patients had mild intraocular inflammation, which was resolved with topical corticosteroids. Six patients had mild to moderate episcleritis and have resolved on topical corticosteroids.
Sharma said the trial is ongoing, with investigators assessing long-term follow-up data; it is scheduled to conclude in 2024. Nine-month data will be presented at the Hawaiian Eye and Reina meeting in January 2024.
ABBV-RGX-314 is also being studied in patients with wet age-related macular degeneration (AMD). In July 2023, several presentations at the American Society of Retinal Specialists' annual meeting found that the therapy is able to provide sustained clinical outcomes in patients with wet AMD. In the phase 2 AAVIATE, ABBV-RGX-314 suprachoroidal delivery was reported to be well tolerated in 85 patients dosed in cohorts 1 to 5. Patients treated with ABBV-RGX-314 had stable vision and retinal thickness across all dose levels.
Another study of subretinal delivery, where the therapy is delivery just under the retina, compared formulations developed from two different manufacturing processes for ABBV-RGX-314. One is a bioreactor process that would be used to manufacture the commercial product.