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Gene Therapy for Diabetic Retinopathy Yields Continued Improvements

Suprachoroidal delivery of RGX-314 has demonstrated safety and efficacy in diabetic retinopathy (DR), according to updated interim data from the phase 2 ALTITUDE trial (NCT04567550).1

The data were reported at the Angiogenesis, Exudation, and Degeneration 2022 conference, February 11-22, 2022, by Michael A. Klufas, M.D., Retina Service, Wills Eye Hospital, assistant professor of ophthalmology, Thomas Jefferson University.

"We are pleased to see that RGX-314 continues to be well tolerated at six months following a one-time, in-office injection, with nearly 50 percent of patients dosed with RGX-314 in Cohort 1 demonstrating a clinically meaningful improvement from baseline" Steve Pakola, MD, chief medical officer, REGENXBIO, said in a statement.1 "We are continuing to enroll patients in Cohorts 2 and 3 and look forward to sharing additional updates from this trial."

Investigators found that 7 patients (47%) of patients in cohort 1 treated with RGX-314 improved by at least 2 steps from baseline on the early treatment of diabetic retinopathy scale (ETDRS-DRSS) at 6 months. One patient treated (7%) has demonstrated a 4-step improvement.At 3 months, 33% of treated patients had reached this milestone and no patients (n = 0/5) in the observational control group have achieved this. One patient treated (7%) has demonstrated a 4-step improvement.The 2-step improvement has been accepted as a pivotal endpoint by the FDA for clinical trials.

READ MORE: Second Pivotal Trial Initiated for Wet AMD Gene Therapy

In the 7 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.

The therapy and its in-office suprachoroidal delivery continues to be well tolerated in the 15 patients in cohort 1 with no treatment-related serious adverse events (AEs) at 6 months and no intraocular inflammation. Serious AEs not related to treatment were reported in 2 patients. One patient experienced a mild case of episcleritis that resolved with topical corticosteroids. Other common AEs related to ocular treatment but not RGX-314 were reported and included mostly mild cases of conjunctival hemorrhage and conjunctival hyperemia.

The open-label, dose-escalation ALTITUDE trial continues to enroll patients with moderately severe or severe nonproliferative DR (NPDR) or mild proliferative DR (PDR) in cohorts 2 and 3 to be treated with 5 x 1011 gc/eye of RGX-314 in patients who are neutralizing antibody (NAb) positive (cohort 3) and negative (cohort 2). The ALTITUDE trial was previously expanded from wet age-related macular degeneration (wet AMD) to include DR in October 2021.2

"I am encouraged by the clinical improvement of disease severity observed in the ALTITUDE trial of RGX-314," Klufas added to the statement.1 "Globally, DR is the leading cause of blindness in working-age adults, and these patients are in need of new treatment options. I look forward to the further investigation of RGX-314 as a potentially compelling treatment option for patients with DR." 

RGX-314 is developed by REGENXBIO in collaboration with AbbVie. The therapy uses the NAV AAV8 vector to deliver a monoclonal antibody fragment gene to inhibit vascular endothelial growth factor (VEGF). The therapy is being evaluated with 2 avenues of administration: standardized subretinal delivery procedure as well as suprachoroidal delivery via the SCS Microinjector®.

REFERENCES
1. REGENXBIO presents positive interim data from phase II ALTITUDE™ trial of RGX-314 for the treatment of diabetic retinopathy using suprachoroidal delivery. News release. REGENXBIO. February 12, 2022. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-presents-positive-interim-data-phase-ii-altitudetm
2. REGENXBIO presents positive initial data from phase II ALTITUDE™ trial of RGX-314 for the treatment of diabetic retinopathy using suprachoroidal delivery at American Society of Retina Specialists Annual Meeting. News release. REGENXBIO. October 9, 2021. http://ir.regenxbio.com/news-releases/news-release-details/regenxbio-presents-positive-initial-data-phase-ii-altitudetm