REGENXBIO Inc. announced additional positive interim 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. The data is being presented at the Angiogenesis, Exudation, and Degeneration 2022 conference by Michael A. Klufas, M.D., Retina Service, Wills Eye Hospital, Assistant Professor of Ophthalmology, Thomas Jefferson University. RGX-314 is being investigated as a potential one-time gene therapy for the treatment of wet age-related macular degeneration and DR.
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 evaluating 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 January 18, 2022, RGX-314 was reported to be well tolerated in Cohort 1. Two serious adverse events were reported in two patients, both of which were not considered drug-related. Among patients in Cohort 1 dosed with RGX-314, no intraocular inflammation was observed. As previously reported, one patient experienced a mild case of episcleritis that resolved with topical corticosteroids. Common ocular treatment emergent adverse events in the study eye through six months were not considered drug-related and were predominantly mild. These included conjunctival hemorrhage and conjunctival hyperemia.
Summary of Data for Cohort 1 at Six Months
At six months, of the 15 patients dosed with RGX-314 in Cohort 1, seven patients (47%) demonstrated a two-step or greater improvement from baseline on the Early Treatment Diabetic Retinopathy Study-Diabetic Retinopathy Severity Scale (DRSS), the study’s primary endpoint, compared to zero of the five patients (0%) in the observational control group. One patient (7%) dosed with RGX-314 continues to demonstrate a four-step improvement. The percentage of Cohort 1 patients dosed with RGX-314 achieving at least two-step improvement at six months in RGX-314 treated eyes (47%) increased from the previously reported three-month results (33%). A 2-step improvement in DRSS has been accepted as a pivotal endpoint by the FDA for DR clinical trials.
In the seven patients who had NPDR (DR severity level 47-53) at baseline, 57% of patients demonstrated a two-step or greater improvement from baseline DRSS at six months after administration of RGX-314. In the eight patients who had PDR (DR severity level ≥ 61) at baseline, 38% of patients demonstrated a two-step or greater improvement at six months after administration of RGX-314.
At six months after administration of RGX-314, Cohort 1 patients demonstrated stable mean change in BCVA of +0.3 letters compared to baseline, while five patients in the observational control arm demonstrated stable mean change in BCVA of -2.0 letters compared to baseline.
