RGX-314 Reduces nAMD Treatment Burden, Shows Disease Improvements


One participant experienced a possibly related serious AE of pigmentary changes in the macula with severe vision reduction.

Jeffrey S. Heier, MD

Jeffrey S. Heier, MD

Credit: Ophthalmic Consultants of Boston

RGX-314 gene therapy (REGENXBIO) was well-tolerated in most participants with neovascular/wet age-related macular degeneration (nAMD) and showed dose-dependent improvements in disease measures and reductions in anti-VEGF injection usage in a phase 1/2a trial (NCT03066258).1

"The publication of the ABBV-RGX-314 Phase I/IIa trial results in The Lancet reinforces the encouraging long-term clinical data observed using subretinal delivery and underscores the potential of ABBV-RGX-314 gene therapy to offer a new approach to the clinical management of wet AMD," primary investigator Jeffrey S. Heier, MD, Director, Vitreoretinal Service and Director, Retina Research, Ophthalmic Consultants of Boston, said in a statement.2 "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. 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."

The open-label trial, conducted across 8 sites in the United States, enrolled 42 participants with nAMD aged 50–89 years who had previously been treated with anti-VEGF injections into 5 dose cohorts. These participants had macular neovascularisation secondary to nAMD with subretinal or intraretinal fluid in the center subfield, were pseudophakic (after cataract removal), and had a best-corrected visual acuity (BCVA) in the study eye between 20/63 and 20/400 (first participant in each cohort)or between 20/40 and 20/400 (other participants).

RGX-314 was administered by subretinal injection without a pre-bleb by a wet-laboratory-trained vitreoretinal surgeon. Participants received either 3 × 109 genome copies per eye in cohort 1, 1 × 1010 in cohort 2, 6 × 1010 in cohort 3, 1·6 × 1011 in cohort 4, or 2·5 × 1011 in cohort 5. Follow-up visits occurred at 1 day and 1 week after administration of RGX-314, and then monthly for 2 years (up to week 106). The trial’s primary outcome was safety of RGX-314 subretinal injection up to week 26.

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Investigators found that there were 20 serious adverse events (AEs) in 13 participants. One, pigmentary changes in the macula with severe vision reduction 12 months post-injection, was possibly related to RGX-314. This participant received 2·5 × 1011 genome copies per eye. Other participants had asymptomatic pigmentary changes in the inferior retinal periphery months after RGX-314 injection most commonly at doses of 6 × 1010 genome copies per eye or higher. Investigators observed no clinically determined immune responses or unexpected inflammation.

Dose responses were seen, with sustained concentrations of RGX-314 protein in aqueous humor in participants that received doses of 6 × 1010 genome copies or higher. These participants had stable or improved BCVA and central retinal thickness. Most participants needed few or no supplemental anti-VEGF-A injections for up to 2 years of follow-up.

"We have started 2024 with strong, positive new data from the ABBV-RGX-314 program, and we believe that there is multi-billion-dollar potential for ABBV-RGX-314 to become a first-in-class gene therapy for wet AMD and the standard of care to treat and prevent progression of diabetic retinopathy," Kenneth T. Mills, President and Chief Executive Officer, REGENXBIO, added.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.”

1. 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
2. REGENXBIO Announces Lancet Publication of Phase I/IIa Study Evaluating ABBV-RGX-314 as a One-Time Gene Therapy for Wet AMD. News release. REGENXBIO. March 28, 2024. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-announces-lancet-publication-phase-iiia-study
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