Peter A. Campochiaro, MD: Phase 1/2a Data on RGX-314 Gene Therapy for Wet AMD

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Peter A. Campochiaro, MD, discusses the safety and tolerability of RGX-314 gene therapy in treating wet AMD and how these results inform pivotal clinical trials.

A single, subretinal administration of ABBV-RGX-314 gene therapy was well-tolerated, with no clinically recognized immune response, in the treatment of neovascular (wet) age-related macular degeneration (nAMD), according to Phase 1/2a trial results.

Published in The Lancet, the two-year data indicate the novel approach may provide a pathway for sustained vascular endothelial growth factor (VEGF)-A suppression with a single dose, potentially safely maintaining vision and reducing treatment burden in nAMD.

In an interview with HCPLive, Peter A. Campochiaro, MD, the director of the retinal cell and molecular laboratory and professor of ophthalmology and neuroscience at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, described the notability of a potential, one-time gene therapy for wet AMD, given the burden resulting from the current treatment landscape.

Treatments for retinal diseases are typically anti-VEGF agents, which reduce leakage and allow for the improvement or maintenance of vision. However, after the antibody that binds the VEGF exits the eye, VEGF levels are raised and most patients require further injections, typically every four to six weeks. Campochiaro noted as “life gets in the way” and the number of injections decreases, many patients lose vision over time.

“Treatments that have greater sustainability, such as RGX-314, where you do a subretinal injection and then the gene that makes the therapeutic protein goes into the cells in the eye, the anti-VEGF protein is constantly being produced in the eye and suppresses the leakage long-term,” Campochiaro told HCPLive. “As a result, patients don’t require the injections they were requiring frequently prior to the gene therapy.”

Another important part of the data was the measurements of the production of the antibody VEGF protein. Lower doses of RGX-314 in the first two study cohorts demonstrated little production of the therapeutic protein and continued to require anti-VEGF injections—on the other hand, cohorts three through five with an increased RGX-314 dose exhibited increases in the anti-VEGF protein and it remained for the two-year study period.

“This is very important because it helps us interpret the results,” Campochiaro told HCPLive. “We know now why the beneficial effects were not there in the first two cohorts, but in cohorts three through five, with the production of the anti-VEGF protein, many of the patients had control of the fluid production and maintenance of vision.”

He indicated the trial results informed the design of the pivotal trial, particularly the range of doses demonstrating the most benefit. Doses in the mid-range demonstrated strong efficacy and safety, but the highest dose led to some patients exhibiting pigmentary changes in the macula, reducing vision.

“Now we know the range of doses that provide the greatest benefit-to-risk ratio,” Campochiaro told HCPLive. “And that's what's being used in the pivotal trials.”

For more insight into the trial results and other news in ophthalmology, watch the full interview with Campochiaro in the above video.


Iapoce C. RGX-314 gene therapy for NAMD well-tolerated in phase 1/2A study. HCP Live. March 28, 2024. Accessed April 3, 2024.

Campochiaro PA, Avery R, Brown DM, et al. Gene therapy for neovascular age-related macular degeneration by subretinal delivery of RGX-314: a phase 1/2a dose-escalation study. Lancet. Published online March 27, 2024. doi:10.1016/S0140-6736(24)00310-6