Suprachoroidal Delivery of RGX-314 for Diabetic Retinopathy: The Phase II ALTITUDE™ Study

Abstract

Purpose : Sustained anti-VEGF delivery has been shown to decrease severity of diabetic retinopathy (DR) and reduce vision threatening complications, yet it is associated with a high treatment burden. RGX-314 is designed as a single gene therapy intervention utilizing the NAV AAV8 vector to deliver a soluble anti-VEGF fab transgene to potentially provide continuous anti-VEGF therapy. This study will evaluate RGX-314 for the treatment of DR without center-involved diabetic macular edema (CI-DME) utilizing an in-office, suprachoroidal delivery.

Methods : ALTITUDE is an open-label, 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 DR (NPDR) or mild proliferative DR (PDR). 20 patients in Cohort 1 were randomized to receive RGX-314 at a dose level of 2.5x10¹¹ genomic copies per eye (GC/eye) versus observational control at a 3:1 ratio. Additional cohorts will include 40 patients randomized to receive RGX-314 at an increased dose level of 5x10¹¹ GC/eye, in which enrollment is ongoing. Patients do not receive prophylactic immune suppressive corticosteroid therapy before or after receiving RGX-314. The primary outcome is the proportion of eyes with 2-step improvement in DR severity scale score (DRSS) at 48 weeks. Secondary outcomes include safety, and development and intervention of DR-related complications.

Results : As of September 29, 2021, RGX-314 was well tolerated in 15 patients in Cohort 1. One serious adverse event was reported in the fellow eye of a patient treated with RGX-314 and is considered not related to RGX-314. No intraocular inflammation was observed on slit-lamp exam. Common adverse events in the study eye were not considered drug-related and were predominantly mild. 5 of the 15 patients (33%) demonstrated a 2-step or greater improvement in DRSS from baseline at three months, compared to 0 of the 5 patients (0%) in the observational control group. In the 7 patients who had NPDR (DRSS 47-53) at baseline, 3 patients (43%) demonstrated a 2-step or greater improvement.

Conclusions : RGX-314 has the potential to provide sustained clinical outcomes in the treatment of diabetic retinopathy with a one-time treatment administered in-office.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.