The Phase 2 Altitude study is an open-label, randomized, controlled, dose-escalation evaluation of RGX-314, evaluating the efficacy, safety, and tolerability of suprachoroidal delivery of RGX-314 in patients with moderately severe/severe non-proliferative diabetic retinopathy or mild proliferative diabetic retinopathy.
A gene therapy evaluated for diabetic retinopathy (DR), RGX-314 (REGENXBIO), may provide sustained clinical outcomes for treating DR. A major advantage is that this treatment can be administered once into the suprachoroidal space in an office setting, which markedly reduces the treatment burden, according to Dr Mark Barakat, Director of Retinal Research Institute, Retinal Consultants of Arizona, Clinical Assistant Professor of Ophthalmology, University of Arizona College of Medicine in Phoenix.
The Phase 2 Altitude study, an open-label, randomized, controlled, dose-escalation evaluation of RGX-314. It was conducted at 18 retina practices nationally and evaluated the efficacy, safety, and tolerability of suprachoroidal delivery of RGX-314 using the SCS Microinjector (Clearside Biomedical) in patients with moderately severe/severe non-proliferative diabetic retinopathy (NPDR) or mild PDR.
Using this treatment, an adeno-associated virus 8 vector delivers a transgene for a soluble anti-vascular endothelial growth factor (VEGF) fab which is designed to provide continuous anti-VEGF therapy.
The Altitude Study had 3 arms. In cohort 1, 20 patients received RGX-314 at a dose level of 2.5x1011 genomic copies/eye (GC/eye) versus observational control at a 3:1 ratio; cohort 2 was comprised of 20 patients who received RGX-314 at an increased dose level of 5x1011 GC/eye versus an observational control at a 3:1 ratio; and cohort 3 included 20 patients who were neutralizing antibody-positive and received RGX-314 at the same dose as cohort 2.
The primary outcome was the proportion of eyes with 2-step improvement in the diabetic retinopathy severity scale score (DRSS) at 48 weeks; the secondary outcomes include safety and development and intervention of diabetic retinopathy-related complications.
In cohort 1, RGX-314 was generally well tolerated in 15 patients. Two unrelated serious adverse events were reported, 1 case of mild episcleritis resolved with topical treatment, and no intraocular inflammation was developed.
Adverse effects were mostly mild and conjunctival haemorrhage and conjunctival hyperaemia.
Seven of the 15 patients (47%) had an improved DRSS score of 2-steps or more compared with baseline at 6 months, compared to none of 5 patients (0%) in the observational control group.
In the 7 patients with NPDR (DRSS 47-53) at baseline, 4 (57%) demonstrated a 2-step or greater improvement at 6 months.
Barakat concluded, “With these encouraging results from cohort 1, we are anxiously awaiting results from cohorts 2 and 3.RGX-314 has the potential to provide sustained clinical outcomes for treating diabetic retinopathy with a one-time treatment administered in-office. This treatment could deliver advantages over conventional treatments that may require repeated, life-long intraocular injections to prevent disease progression.”