One-Time Gene Therapy Injection Reduces Treatment Burden in AMD

A one-time gene therapy injection, RGX-314 (AbbVie), may provide sustained clinical results for patients with neovascular age-related macular degeneration (AMD), according to a paper presented at the American Society of Retina Specialists meeting, held in Seattle, July 28 to August 1, 2023. Those who received the single, in-office treatment had stable vision and reduced treatment burden.

Currently, the standard for nAMD treatment involves recurrent injections of antivascular endothelial growth factor (anti-VEGF). A one-time gene therapy could provide similar results via a recombinant adeno-associated virus-8 (AAV8) neutralizing antibody (NAb) vector. A Phase I/IIa trial and follow-up has indicated the treatment can aid anatomy and vision through 4 years with subretinal delivery.

Researcher David Boyer, MD, who specializes in retinal diseases at Retina-Vitreous Associates Medical Group in Los Angeles, evaluated the suprachoroidal delivery of the one-time gene therapy. A total of 115 patients with wet AMD divided into 6 cohorts participated in the study. Groups 1 and 2 were randomly assigned to receive either RGX-314 or monthly 0.5 mg ranibizumab intravitreal injections, at a 3:1 ratio. All other cohorts received RGX-314. For cohort 6, treatment was followed with prophylactic ocular steroids.

The one-time gene therapy treatment was evaluated at weeks 40 through 52 for presence of adverse events, best corrected visual acuity (BCVA), central retinal thickness (CRT) and need for anti-VEGF injections. No cases of chorioretinal vasculitis, occlusion, and hypotony occurred.

“As of August 1, 2022, RGX-314 suprachoroidal delivery was reported to be well tolerated across 85 patients dosed in Cohorts 1-5,” Dr Boyer explained. “Fifteen SAEs were reported, none of which were considered related to RGX-314.”

Some patients managed with RGX-314 who received 2.5×1011 genomic copies per eye (GC/eye) or 5.0×1011 GC/eye reported mild intraocular inflammation. The inflammation was mild to moderate at the third dose level, which was 1.0×1012 GC/eye, in cohort 4. Topical corticosteroids resolved these symptoms.

Cohort 4 experienced the greatest reduction in treatment burden. Patients had 85% less injection rate over the course of a year. Two in 3 patients did not need injections for 6 months. The presence of baseline AAV8 neutralizing antibodies did not appear to change outcomes.