A Promising Shift in Wet AMD Treatment
ABBV-RGX-314, a groundbreaking gene therapy under development by RegenxBio and AbbVie, has the potential to transform wet age-related macular degeneration (wet AMD) management. By utilizing an adeno-associated virus serotype 8 (AAV8) vector to deliver a gene encoding an anti-VEGF monoclonal antibody fragment, ABBV-RGX-314 offers a novel approach to sustain VEGF suppression with a single treatment. Two delivery methods are under investigation: subretinal and suprachoroidal administration, each designed to address the significant treatment burden of frequent anti-VEGF injections while reducing the risk for adverse events such as intraocular inflammation.
Clinical Progress and Key Findings
In a Phase I/IIa study (NCT03066258), ABBV-RGX-314 demonstrated safety and efficacy through subretinal delivery. Patients receiving the gene therapy showed stable or improved best-corrected visual acuity (BCVA) and central retinal thickness for up to two years with minimal need for supplemental anti-VEGF injections. Published in The Lancet, these results laid the foundation for pivotal clinical trials.
Currently, two Phase IIb/III trials—ATMOSPHERE and ASCENT—are evaluating subretinal ABBV-RGX-314 against standard anti-VEGF treatments such as ranibizumab and aflibercept. These randomized, controlled studies aim to determine changes in BCVA at 54 weeks, with global regulatory submissions expected in 2025-2026.
The suprachoroidal approach is being assessed in the AAVIATE trial (NCT04514653), which evaluates the safety and efficacy of ABBV-RGX-314 delivered using the Clearside Suprachoroidal Space (SCS) Microinjector®. Interim results from AAVIATE revealed promising outcomes: an 80% reduction in annualized injection rates and a 50% injection-free rate at six months post-treatment. Importantly, intraocular inflammation, while observed at higher doses, resolved with topical corticosteroids, showing that the therapy is well-tolerated.
A Transformative Option for Patients
The potential of ABBV-RGX-314 as a gene therapy that provides consistent therapeutic anti-VEGF levels could redefine wet AMD care, offering sustained VEGF suppression and a significantly reduced treatment burden. For patients, this means the possibility of long-term visual stability without the logistical and emotional strain of frequent injections.
Looking Ahead
With robust clinical data and a strategic focus on both subretinal and suprachoroidal delivery, ABBV-RGX-314 is positioned as a leading candidate for first-in-class gene therapy in wet AMD. If successful, this therapy could set a new standard in retinal care, addressing both medical and practical barriers in managing this chronic, vision-threatening condition.
Reference
Gene therapy for neovascular age-related macular degeneration by subretinal delivery of RGX-314: a phase 1/2a dose-escalation study
Campochiaro, Peter A et al.
The Lancet, Volume 403, Issue 10436, 1563 – 1573