REGENXBIO's ABBV-RGX-314, an investigational adeno-associated virus (AAV8) vector-based gene therapy, has demonstrated a significant reduction in the need for anti-VEGF injections in patients with bilateral wet age-related macular degeneration (wet AMD). The Phase 2 substudy (NCT03999801) results, presented at the American Academy of Ophthalmology (AAO) 2024 meeting, highlight the potential of ABBV-RGX-314 as a one-time treatment option for patients with this debilitating condition.
The substudy involved patients who had previously been treated with ABBV-RGX-314 in one eye and subsequently received the gene therapy in their fellow eye. ABBV-RGX-314 was administered subretinally at a dose of 1.3x10^11 GC/eye, approximately one year or more after the initial treatment. The primary outcome assessed was the change in anti-VEGF injection frequency.
Significant Reduction in Treatment Burden
Data from nine patients with nine months of follow-up showed a remarkable 97% decrease in the annualized anti-VEGF treatment burden. Furthermore, 78% of patients were completely free of anti-VEGF injections after receiving the gene therapy in their fellow eye. None of the patients required more than one supplemental anti-VEGF injection during the nine-month period. These findings suggest a substantial reduction in the treatment burden typically associated with wet AMD management.
Sustained Visual Acuity and Retinal Thickness
In addition to the reduced injection frequency, patients maintained stable best-corrected visual acuity (BCVA) and central retinal thickness (CRT) at nine months post-treatment. This indicates that ABBV-RGX-314 not only reduces the need for frequent injections but also helps preserve vision and retinal structure.
Safety and Tolerability
ABBV-RGX-314 was reported to be well-tolerated in the fellow eyes, with no serious adverse events (AEs) related to the gene therapy. Common AEs included mild retinal pigmentary changes in the periphery and post-operative conjunctival hemorrhage, all of which resolved within days or weeks. Notably, no additional prophylactic steroids were used in the substudy beyond those typically used in vitrectomy surgery.
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, leading to suboptimal real-world vision outcomes with current standard of care," said Arshad Khanani, MD, Director of Clinical Research at Sierra Eye Associates. "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."
Implications for Wet AMD Treatment
Wet AMD is a leading cause of vision loss, characterized by the formation of new, leaky blood vessels in the retina. Current standard of care involves frequent anti-VEGF injections to prevent disease progression. However, the burden of frequent injections can lead to suboptimal adherence and vision decline over time. ABBV-RGX-314 offers a potential alternative by providing a one-time treatment that reduces the need for repeated injections, potentially improving long-term visual outcomes for patients with bilateral wet AMD.
Competition in the Gene Therapy Landscape
ABBV-RGX-314 is not the only gene therapy being developed for wet AMD. 4D Molecular Therapeutics is evaluating 4D-150, a dual-mechanism gene therapy, in the Phase 1/2 PRISM clinical trial (NCT05197270). Adverum Biotechnologies' ixoberogene soroparvovec (ixo-vec) recently received regenerative medicine advanced therapy designation from the FDA, indicating the growing interest and investment in gene therapy approaches for wet AMD.
