RGX-314 Gene Therapy for nAMD Well-Tolerated in Phase 1/2a Study

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A single administration of ABBV-RGX-314 was generally well tolerated, with little to no supplemental anti-VEGF injections required in most patients at two years.

Subretinal delivery of ABBV-RGX-314, a potential one-time 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 results published in The Lancet.1

The publication detailed two-year data suggesting the novel approach of RGX-314 for sustained vascular endothelial growth factor (VEGF)-A suppression, with the potential to safely maintain vision and reduce treatment burden in patients with nAMD after a single dose.

“Wet AMD is a chronic, life-long disease and real-world evidence shows patients are losing significant vision over time, and the burden of frequent anti-VEGF injections needed to manage their wet AMD is a major reason why,” Jeffrey S. Heier, MD, director of the vitreoretinal service and retina research, Ophthalmic Consultants of Boston and the primary study investigator, said in a statement.2 “A single treatment of ABBV-RGX-314 that can potentially provide long-lasting treatment outcomes and a strong safety profile would offer a novel approach to treating this serious and blinding disease.”

Frequent anti-VEGF-A injections lessen the risk of rapid, severe vision loss among patients with nAMD, but the frequency-related burden could lead to undertreatment, and thus, vision loss over time.3 Sustained suppression of the VEGF-A pathway may provide the maintenance of vision and a reduction in the associated treatment burden.

RGX-314, an adeno-associated virus serotype 8 vector expressing an anti-VEGF-A antigen-binding fragment, is developed to allow continuous VEGF-A suppression after a single administration.2 REGENXBIO is investigating two separate routes of administration of RGX-314 to the eye, including standard subretinal delivery and suprachoroidal delivery.

Current results from the phase 1/2a, open-label, dose-escalation study reported the safety and efficacy of the subretinal delivery of five dose cohorts of RGX-314 for patients with nAMD.1 Between May 2017 and May 2019, investigators screened 110 patients with previously treated nAMD for eligibility criteria. The trial’s primary outcome was the safety of RGX-314 delivered by subretinal injection up to week 26.

After enrolling 68 individuals into the trial, 42 participants met the required anatomic response to intravitreal ranibizumab and received a single RGX-314 injection (dose range 3x109 to 2.5x1011 genome copies per eye). Participants were observed 1 day and 1 week after administration, then monthly for 2 years.

Analyses revealed 20 serious adverse events in 13 participants, with one event considered potentially related to RGX-314. The event was pigmentary changes in the macular with severe vision reduction 12 months after injection of RGX-314 at a dose of 2.5 x 1011 genome copies per eye.

Heier and colleagues observed asymptomatic pigmentary changes in the inferior retinal periphery months after subretinal RGX-314, primarily at doses of 6x1010 genome copies per eye or higher. In addition, the analysis demonstrated no clinically determined immune responses or inflammation outside of those expected after routine vitrectomy.

Overall, the doses of 6 x 1010 genome copies per eye or higher led to sustained concentrations of RGX-314 protein in the aqueous humor, as well as stable or improved BCVA and central retinal thickness, with little to no supplemental anti-VEGF injections administered in most participants.

Heier and colleagues noted these results inform the pivotal program to assess RGX-314 for the treatment of nAMD further. Two pivotal trials, ATMOSPHERE and ASCENT, are currently evaluating RGX-314 in patients with wet AMD with on-target enrollment.

RegenXBio expects these data to support regulatory submission with the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in late 2025 through early 2026.2

“To have these Phase I/IIa data published in The Lancet highlights the groundbreaking work of our scientists and investigators, and further validates the clinically transformative nature of ABBV-RGX-314 as a potential one-time gene therapy for wet AMD that may help patients maintain or improve their vision,” Kenneth T. Mills, president and chief executive officer of REGENXBIO, added in a statement.2


  1. Campochiaro PA, Huddleston SM, Ho AC, Brown DM, Avery R. Gene therapy for neovascular age-related macular degeneration by subretinal delivery of RGX-314: a phase 1/2a dose-escalation study. The Lancet. March 27, 2024. Accessed March 28, 2024.
  2. Regenxbio announces lancet publication of phase I/IIA study evaluating ABBV-RGX-314 as a one-time gene therapy for WET AMD. Regenxbio Inc. March 28, 2024. Accessed March 28, 2024.
  3. Campochiaro PA, Aiello LP, Rosenfeld PJ. Anti-Vascular Endothelial Growth Factor Agents in the Treatment of Retinal Disease: From Bench to Bedside. Ophthalmology. 2016;123(10S):S78-S88. doi:10.1016/j.ophtha.2016.04.056