For individuals and families navigating the challenges of inherited retinal diseases (IRDs), advancements in gene therapy represent a beacon of hope. While many IRDs are genetic, the progress in gene therapy for other retinal conditions, such as wet age-related macular degeneration (AMD), often signals broader scientific momentum and potential future applications that could benefit the entire retinal disease community. The news that RegenxBio is expanding its pivotal trials globally for its wet AMD gene therapy, ABBV-RGX-314, is a significant development, as it moves closer to potentially offering a one-time treatment that could reduce the burden of frequent eye injections for millions.
Key Developments in Wet AMD Gene Therapy
RegenxBio announced in May 2023 that it is globally expanding pivotal trials for ABBV-RGX-314, an investigational gene therapy for wet AMD. This expansion involves the transfer of Investigational New Drug (IND) applications to AbbVie, which will now lead the regulatory process and be responsible for the global development and commercialization of ABBV-RGX-314. Both companies will continue to collaborate on additional clinical trials for the gene therapy.
ABBV-RGX-314, formerly known as RGX-314, is being developed as a novel, one-time subretinal injection. It utilizes a NAV® adeno-associated virus (AAV8) vector to deliver a gene encoding a monoclonal antibody fragment. This modified AAV vector is designed to produce a protein that neutralizes vascular endothelial growth factor (VEGF) activity, thereby blocking the growth of new, leaky blood vessels and preventing fluid accumulation in the retina.
The ongoing Phase 2b/3 ATMOSPHERE (NCT04704921) and Phase 3 ASCENT (NCT05407636) pivotal trials are evaluating the safety and efficacy of ABBV-RGX-314 for wet AMD. These studies are assessing two doses of the gene therapy compared to an active comparator. The trial is also assessing the safety, efficacy, and immunogenicity of ABBV-RGX-314 via subretinal delivery into the eyes of patients with bilateral disease who have already received a subretinal injection. According to Clinical Trials, the study is slated for completion in December 2028.
What This Means for Patients and Families
Wet AMD is a leading cause of vision loss, and its current standard of care involves frequent, often monthly, anti-VEGF injections directly into the eye. While effective, these injections can be uncomfortable and inconvenient, posing a significant burden on patients and their families. A one-time gene therapy treatment like ABBV-RGX-314 has the potential to significantly reduce or even eliminate the need for these frequent injections, offering a more sustained and less burdensome treatment option.
Although wet AMD is not an inherited retinal disease, the success and expansion of gene therapy trials in this area demonstrate the growing potential of gene therapy as a therapeutic modality for various retinal conditions. This progress fuels optimism within the broader IRD community, as research and development in one area of ocular gene therapy can often pave the way for breakthroughs in others. The focus on reducing treatment burden is also a shared goal across many chronic eye conditions.
Looking Ahead
The global expansion of these pivotal trials brings ABBV-RGX-314 closer to potential regulatory submission and, ultimately, to patients. The collaboration between RegenxBio and AbbVie, with AbbVie taking the lead on global development and commercialization, underscores the significant investment and commitment to advancing this potential one-time gene therapy. The IRD community will continue to monitor these developments, hopeful that such advancements will lead to improved quality of life for all affected by retinal diseases.