UC Davis Eye Center Administers Wet AMD Gene Therapy ABBV-RGX-314 to Participant in Phase 3 Study

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It was the first time the Eye Center treated a patient with a gene therapy.

University of California, Davis (UC Davis) Eye Center has treated a patient with wet age-related macular degeneration (AMD) with ABBV-RGX-314 (RGX-314), an investigational adeno-associated virus (AAV) vector-based gene therapy, as part of the phase 3 ASCENT clinical trial (NCT05407636).1

RGX-314, which is being developed in a collaboration between REGENXIO and AbbVie, is delivered via REGENXBIO’s NAV AAV8 vector.2 It encodes for an antibody fragment meant to inhibit the vascular endothelial growth factor (VEGF) pathway that causes leaky blood vessels to grow in patients with wet AMD.

Notably, this patient’s treatment was the first time that UC Davis Eye Center has utilized gene therapy.1 The administration procedure, which involves a vitrectomy and a subretinal injection of the AAV vector, was carried out by Glenn Yiu, MD, PhD, the principal investigator for the clinical trial and a professor in the UC Davis Eye Center, in July 2023. Although this procedure is more complex than the procedure used to administer the standard of care therapy, antiVEGF injections, it is expected that RGX-314 could serve as a 1-time treatment, replacing repeated antiVEGF injections. 

“The current treatments for wet AMD may be life-long, and injections can be as frequent as every month,” Yiu said in a statement.1 “If approved, a gene therapy solution has the potential to maintain vision while reducing the number of injections, by allowing the eye to continuously produce the medicine on its own.”

The multicenter, randomized, partially masked ASCENT clinical trial is being conducted at 92 other sites in the United States in addition to the UC Davis Eye Center. Several sites in Canada are also recruiting patients for the trial. Thus far, UC Davis Health has enrolled 3 patients for ASCENT in total; additional patient enrollment is planned.

ASCENT as a whole is expected to enroll approximately 465 patients aged 50 to 89 years across its study locations. The study includes 2 treatment arms that will dose patients with a lower and higher dose of RGX-314, respectively. A third arm is also included in the trial that will serve as an active comparator. This control arm will treat patients with the antiVEGF injection Aflibercept (EYLEA) at a dose of 2.0 mg (0.05 mL solution) via intravitreal injection monthly for 3 months, and then approximately every 8 weeks. The study’s primary end point is the mean change from baseline in best corrected visual acuity (BCVA) at 54 weeks posttreatment. 

In addition to ASCENT, RGX-314 is also being evaluated for the treatment of wet AMD in the phase 2b/3 ATMOSPHERE study (NCT04704921), a phase 2 bridging study (NCT04832724), and the phase 2 AAVIATE study (NCT04514653), which is utilizing a suprachoroidal delivery method rather than a subretinal method.2 RGX-314 is also being evaluated for the treatment of diabetic retinopathy in the phase 1/2 ALTITUDE study (NCT04567550). In February 2023, REGENXBIO announced that in the phase 2 bridging study, RGX-314 demonstrated consistent results between product manufactured with a new proprietary bioreactor platform process called NAVXpress and product produced with an adherent cell culture process. ASCENT and ATMOSPHERE are also including the use of material produced with the NAVXpress platform process.2

“It is noteworthy for patients in Northern California that UC Davis Health is doing experimental ocular gene therapy studies in the Department of Ophthalmology and Vision Sciences,” Paul Sieving, MD, PhD, the former director of the National Eye Institute and a current professor of ophthalmology at UC Davis Health, added to the statement.1 “What excites me most about this is the potential of Dr. Yiu’s work to reduce the repeated eye injections currently required for wet age-related macular degeneration."

REFERENCES
1. Eye Center tests experimental gene therapy for wet age-related macular degeneration. News release. UC Davis Health. August 29, 2023. Accessed August 30, 2023.https://health.ucdavis.edu/news/headlines/eye-center-tests-experimental-gene-therapy-for-wet-age-related-macular-degeneration/2023/08
2. REGENXBIO presents interim data from phase II bridging study evaluating the clinical performance of RGX-314 using the NAVXpress manufacturing platform process. News release. REGENXBIO Inc. February 11, 2023. Accessed February 13, 2023. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-presents-interim-data-phase-ii-bridging-study
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