Initial data from the ongoing Phase II ALTITUDE™ trial of RGX-314 for the treatment of diabetic retinopathy (DR) without center-involved diabetic macular edema (CI-DME) using in-office suprachoroidal delivery was presented at the American Society of Retina Specialists (ASRS) Annual Meeting by Dennis Marcus, MD, FASRS, President, Southeast Retina Center. RGX-314 is a potential one-time gene therapy in clinical development for the treatment of wet age-related macular degeneration and DR.
“DR can start in young adulthood and often progresses quickly, leading to vision-threatening complications, including diabetic macular edema (DME) and neovascularization that can lead to vision loss,” said Dr. Marcus. “Current treatment options include ‘watchful waiting,’ treatment requiring repeated anti-VEGF injections, retinal laser or surgical treatment. This first look at the ALTITUDE trial data is promising, as it shows not only clinical improvement in disease severity as measured by the ETDRS-DRSS, but also that this treatment is well tolerated in patients.”
Study Design and Safety Update from Phase II ALTITUDE Trial of RGX-314 for the Treatment of DR Using Suprachoroidal Delivery
ALTITUDE is a multi-center, open-label, randomized, controlled dose-escalation trial that will evaluate the efficacy, safety and tolerability of suprachoroidal delivery of RGX-314 using the SCS Microinjector® in patients with a DR diagnosis of moderately severe or severe nonproliferative diabetic retinopathy (NPDR) or mild proliferative diabetic retinopathy (PDR). Twenty patients in Cohort 1 were randomized to receive RGX-314 at a dose level of 2.5×1011 genomic copies per eye (GC/eye) versus observational control at a 3:1 ratio. Cohort 2 will include 20 patients randomized to receive RGX-314 at an increased dose level of 5×1011 GC/eye versus observational control at a 3:1 ratio. Cohort 3 is designed to evaluate RGX-314 at the same dose level as Cohort 2 in 20 patients who are neutralizing antibody (NAb) positive. Enrollment is ongoing in Cohorts 2 and 3. Patients in this trial do not receive prophylactic immune suppressive corticosteroid therapy before or after administration of RGX-314.
As of September 29, 2021, RGX-314 was reported to be well tolerated in the 15 patients dosed with RGX-314 in Cohort 1. One serious adverse event was reported in one patient dosed with RGX-314, which occurred in the patient’s untreated fellow eye and is considered not related to RGX-314. Among patients in Cohort 1 dosed with RGX-314, no intraocular inflammation was observed on slit-lamp examination. One patient experienced a mild case of episcleritis that resolved with topical corticosteroids. Common ocular treatment emergent adverse events in the study eye were not considered drug-related and were predominantly mild. These included conjunctival hemorrhage and conjunctival hyperemia.
Summary of Data for Cohort 1 at Three Months
Of the 15 patients dosed with RGX-314 in Cohort 1, five patients (33%) demonstrated a two-step or greater improvement from baseline on the Early Treatment Diabetic Retinopathy Study-Diabetic Retinopathy Severity Scale (ETDRS-DRSS) at three months, compared to zero of the five patients (0%) in the observational control group. One patient dosed with RGX-314 had a four-step improvement.
In the seven patients who had NPDR (DR severity level 47-53) at baseline, three patients (43%) demonstrated a two-step or greater improvement at three months after administration of RGX-314. In the eight patients who had PDR (DR severity level ≥ 61) at baseline, two patients (25%) demonstrated a two-step or greater improvement at three months after administration of RGX-314.
About RGX-314
RGX-314 is being investigated as a potential one-time treatment for wet AMD, diabetic retinopathy, and other chronic retinal conditions. RGX-314 consists of the NAV AAV8 vector, which encodes an antibody fragment designed to inhibit vascular endothelial growth factor (VEGF). RGX-314 is believed to inhibit the VEGF pathway by which new, leaky blood vessels grow and contribute to the accumulation of fluid in the retina.
REGENXBIO is advancing research in two separate routes of administration of RGX-314 to the eye, through a standardized subretinal delivery procedure as well as delivery to the suprachoroidal space. REGENXBIO has licensed certain exclusive rights to the SCS Microinjector® from Clearside Biomedical, Inc. to deliver gene therapy treatments to the suprachoroidal space of the eye.
