Data presented at the 2024 American Academy of Ophthalmology (AAO) meeting highlighted positive results from a phase 2 fellow eye sub-study evaluating ABBV-RGX-314 for bilateral wet age-related macular degeneration (wet AMD). The study, which assessed the safety and efficacy of subretinal delivery of ABBV-RGX-314, suggests the gene therapy's potential as a one-time treatment option for patients facing frequent injections in both eyes.
Fellow Eye Sub-Study Design and Results
The fellow eye sub-study involved patients with pre-existing wet AMD who had previously received ABBV-RGX-314 in one eye during a phase 1/2a trial or bridging studies. The second eye was treated with ABBV-RGX-314 approximately one year or more after the initial treatment. The data, collected at 9 months post-administration in nine patients, revealed a significant reduction in treatment burden. Prior to ABBV-RGX-314 administration, patients had received an average of nine anti-VEGF injections in the fellow eye within the year.
Key findings from the Phase 2 fellow eye sub-study include:
- A 97% reduction in annualized anti-VEGF treatment burden.
- 100% of patients required either zero or one supplemental injection.
- 78% of patients were completely injection-free.
Patients also maintained stable best-corrected visual acuity (BCVA) and central retinal thickness (CRT) throughout the 9-month period. The levels of aqueous protein produced by ABBV-RGX-314 were similar in both treated eyes.
Safety Profile
As of September 11, 2024, ABBV-RGX-314 demonstrated a favorable safety profile in the treated fellow eyes. No drug-related serious adverse events were reported, and there were no instances of intraocular inflammation, chorioretinitis, vasculitis, occlusion, or hypotony. Prophylactic steroids were not used in the trial, except for those typically administered during vitrectomy surgery. Common adverse events, such as mild retinal pigmentary changes in the periphery and post-operative conjunctival hemorrhage, resolved within days to weeks.
Expert Commentary
"The majority of our patients with wet AMD eventually have bilateral disease and face a substantial treatment burden with frequent lifelong injections in both eyes," said Arshad Khanani, MD, MA, FASRS, Director of Clinical Research at Sierra Eye Associates. "This leads to suboptimal real-world vision outcomes with current standard of care. The fellow eye dosing data with ABBV-RGX-314 is a milestone for the field of gene therapy for common retinal diseases, as this is the first time we have performed bilateral treatment for wet AMD patients. These results, combined with the durable treatment effect up to four years shown in long-term follow up, highlight the potential of ABBV-RGX-314 as a one-time effective treatment option for patients with wet AMD."
