RGX-314 gene therapy, a treatment for wet age-related macular degeneration delivered subretinally, showed dose-dependent sustained/improved vision and a good safety profile.
This article was reviewed by Jeffrey S. Heier, MD
RGX-314 (REGENXBIO) gene therapy, delivered subretinally to patients with neovascular age-related macular degeneration (AMD), who required a large number of prior injections of anti-vascular endothelial growth factor (VEGF) annually, provided a marked decrease in the number of injections needed and retained or improved the vision and anatomy in this challenging patient population.
RGX-314 uses a proprietary gene delivery platform that is hypothesized to deliver longer and higher protein expression with a lower immune response that earlier generation adeno associated viruses (AAVs) used for gene therapy.
“The AAV8 vector is encoded to deliver a gene that leads to anti-VEGF antibody fragment protein production within the retina,” said Jeffrey S. Heier, MD, co-president and director of Retinal Research, Ophthalmic Consultants of Boston.
All 42 patients included in this study had undergone previous treatment for neovascular AMD and had a “high need” for anti-VEGF therapy, i.e., patients received more than 30 injections on average prior to coming in and an average of 9.6 annualized injections in the year prior to RGX-314.
In addition, the included patients had to have shown an anatomic response to anti-VEGF therapy during screening. After RGX-314 was delivered to the subretinal space, the patients were evaluated monthly to assess safety and the need for additional anti-VEGF therapy, Dr. Heier noted.
Re-treatment with an anti-VEGF drug could be provided beginning at four weeks after RGX-314 was delivered and then as needed every four weeks thereafter based on physician discretion, Dr. Heier explained. The criteria for retreatment was per investigator discretion which included choroidal neovascularization-related increased, new, or persistent fluid; vision loss of five or more letters as a result of fluid, or a new ocular hemorrhage.
Following delivery of RGX-314, Dr. Heier reported that the drug was well tolerated. No serious adverse events were reported; most adverse events were classified as mild, i.e., grade 1 in 79% of cases. In addition, no clinically determined immune responses occurred.
Two deaths that occurred were not related to RGX-314. Two serious adverse effects that were related to the delivery procedure were reported, specifically, a peripheral retinal detachment that was repaired successfully and a case of endophthalmitis that occurred after collection of an aqueous sample.
“We observed a dose-dependent increase in RGX-314 protein across the five dose cohorts,” he reported. The protein levels were measured in aqueous samples collected one month after delivery of RGX-314.
Cohort 3, which included six eyes treated with a dose of 6 x 1010 genome copies (GC)/eye, did well.
“Cohort 3 had a gain in vision of +9 letters and stable anatomy of -40 μm over 18 months despite relatively few injections,” Dr. Heier reported.
Three of the six patients in this cohort were injection-free at 18 months. They had a mean increase of +11 letters of vision at 18 months and a concomitant mean decrease in the central retinal thickness of -21 μm. The RGX-314 protein levels were sustained over one year.
Related: Decreasing burden of nAMD therapy