Suprachoroidal Delivery of RGX-314 Gene Therapy for Neovascular AMD: The Phase II AAVIATE™ Study

Abstract

Purpose : Intravitreal anti-VEGF injections are approved to treat neovascular age-related macular degeneration (nAMD), yet real world evidence shows patients lose vision over time due to undertreatment. RGX-314 is designed as a single gene therapy intervention utilizing an adeno-associated virus 8 (AAV8) vector, to deliver an anti-VEGF fab transgene, potentially producing continuous anti-VEGF therapy in the eye. Initial data from the AAVIATE trial has provided encouraging evidence of RGX-314 as a potential treatment of nAMD using an in-office, suprachoroidal delivery.

Methods : AAVIATE is an open-label trial that will evaluate the efficacy, safety and tolerability of suprachoroidal delivery of RGX-314 using the SCS Microinjector®. 20 patients in Cohort 1 and 20 patients in Cohort 2 were randomized to receive RGX-314 at a dose level of 2.5x10¹¹ and 5x10¹¹ genomic copies per eye (GC/eye), respectively, versus monthly 0.5 mg ranibizumab intravitreal injection at a 3:1 ratio. Cohort 3 is evaluating RGX-314 at the same dose level as Cohort 2 in 20 patients who are neutralizing antibody (NAb) positive. The primary outcome is the mean change in BCVA at 9 months. Secondary outcomes include safety, central retinal thickness (CRT), and additional anti-VEGF injections needed post-RGX-314.

Results : As of November 4, 2021, RGX-314 was well tolerated in 50 patients dosed in Cohorts 1-3. Four serious adverse events were reported in 4 patients, all of which were considered not related to RGX-314. For the total group of Cohorts 1 and 2, all common treatment emergent adverse events (TEAEs) through 6 months in the study eye were mild. Mild intraocular inflammation observed on slit-lamp examination in 7 of 30 patients (23%) was reported at similar incidence across both dose levels, and all cases resolved within days to weeks on topical corticosteroids. Patients dosed with RGX-314 in Cohorts 1 and 2 demonstrated stable BCVA and CRT at 6 months and had a meaningful reduction in anti-VEGF treatment burden (>70%). 4 of 14 patients (29%) and 6 of 15 patients (40%) in Cohorts 1 and 2, respectively, received no anti-VEGF injections over 6 months following RGX-314 administration.

Conclusions : Suprachoroidal RGX-314 has the potential to provide sustained clinical improvements in the treatment of nAMD with a one-time in-office treatment.

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