Patients treated with RGX-314 also had stable BCVA and central retinal thickness.
Suprachoroidal delivery of RGX-314 using the SCS Microinjector was well tolerated and efficacious in patients with wet age-related macular degeneration (AMD) according to data from the phase 2 AAVIATE study (NCT04514653).1
The data, from 50 patients in 3 cohorts in the multi-center, open-label, randomized, active-controlled, dose-escalation study, were presented at the Retina Society 54th Annual Scientific Meeting by Nikolas J.S. London, MD, FACS, president and director, clinical research, Retina Consultants San Diego.2
"We are pleased to share initial data from the Phase II AAVIATE trial, and we are encouraged by the emerging clinical profile of RGX-314 for the treatment of wet AMD using suprachoroidal delivery, a delivery mechanism which we believe could provide access to gene therapy treatment in all settings of patient care," said Steve Pakola, MD, chief medical officer, REGENXBIO, in a statement.1 "The observed stability of visual acuity and retinal thickness in the backdrop of reduced anti-VEGF injections is encouraging at this first dose level. We look forward to further enhancing our understanding of the potential of RGX-314 when delivered to the suprachoroidal space, as we continue to evaluate two higher dose levels in this trial."
In cohort 1, 20 patients were randomized to receive 2.5 x 1011 GC per eye versus monthly 0.5 mg ranibizumab intravitreal injection at a 3:1 ratio. In cohort 2, 20 patients were randomized to receive 5 x 1011 GC per eye versus monthly 0.5 mg ranibizumab intravitreal injection at a 3:1 ratio. Cohort 3 evaluated patients who were neutralizing antibody (NAb) positive and treated with the 5 x 1011 GC per eye dose. No patients received prophylactic immune suppressive corticosteroid therapy before or after treatment.
RGX-314 has been well tolerated across all cohorts. Four serious adverse events (AEs) occurred but were deemed unrelated to treatment, including 1 death. Treatment-emergent AEs in cohort 1 included conjunctival hemorrhage, worsening of wet AMD, conjunctival hyperemia, and dry eye. In addition, mild intraocular inflammation in 4 of 15 patients. All cases were short term and resolved with topical corticosteroids.
Stable visual acuity was seen in 14 patients in cohort 1, with a mean best-corrected visual acuity (BCVA) change of –2.8 letters (95% CI; –7.0 to 1.4) from baseline to 6 months and –0.6 letters (95% CI; –5.2 to 4.0) from week 1 to 6 months. Stable central retinal thickness (CRT) was also observed, with a mean change of –2.5 µm (95% CI; –27.1, 22.0) at 6 months from baseline. Five patients receiving ranibizumab had a mean BCVA change of +6.8 letters (–3.3 to 16.9) at 6 months from baseline and +3.0 letters (95% CI; 4.7 to 10.7) from week 1. These patients also had a stable CRT, with a mean change of -22.2 µm (95% CI; –41.6 to –2.8) from baseline to 6 months.
Participants also had a 75.9% reduction in anti-vascular endothelial growth factor (anti-VEGF) treatment burden following treatment with RGX-314, with 4 out of 14 participants discontinuing anti-VEGF injections for 6 months after RGX-314 treatment. These participants also had stable visual acuity (BCVA mean change; +1.3 [95% CI; –5.7 to 8.2]) and CRT (mean change, –5.8 µm [95% CI, –49.5 to 38.0).
REGENXBIO also announced that the AAVIATE study has expanded to include 2 additional cohorts at a third dose level of 1 x 1012 GC per eye. The new fourth cohort will enroll 15 patients and the fifth cohort will enroll 20 NAb positive patients at the same dose level.
"These are the first data ever reported from a gene therapy delivered to the suprachoroidal space of the eye in a clinical trial," London added to the statement.1 "The data from patients in Cohort 1 at six months after RGX-314 administration demonstrate the potential benefit of one-time administration of RGX-314 to the suprachoroidal space for the treatment of wet AMD. I look forward to seeing additional data from the AAVIATE trial."