REGENXBIO’s Wet AMD Gene Therapy Continues to Show Stable BCVA, Reduced Treatment Burden


Updated data from the AAVIATE trial were presented at the Hawaiian Eye and Retina meeting.

ABBV-RGX-314 gene therapy had a positive safety profile and reduced treatment burden in patients with wet age-related muscular dystrophy (AMD) treated in the phase 2 AAVIATE trial (NCT04514653).1

"The potential of ABBV-RGX-314 to transform the way chronic retinal conditions are treated has been demonstrated in multiple trials using both subretinal and suprachoroidal delivery, and these latest interim results from the AAVIATE trial continue to support this outlook," Steve Pakola, MD, Chief Medical Officer, REGENXBIO, said in a statement.1 "One-time, in-office treatment with ABBV-RGX-314 continues to be well tolerated in patients with wet AMD. We are pleased that dose level 3 in this trial has shown the highest reduction in treatment burden with zero cases of inflammation observed in patients who received prophylactic short-course topical steroids. We are encouraged by this data as part of the global ABBV-RGX-314 program."

The multicenter, randomized, dose-escalation, open-label, active-controlled AAVIATE trial has treated 106 patients with wet AMD across 3 dose levels as of November 6, 2023. The trial is evaluating suprachoroidal delivery of ABBV-RGX-314 for efficacy, safety, and tolerability. The primary endpoint of the trial is mean change in best corrected visual acuity (BCVA) at Week 40 from baseline, compared to patients receiving monthly injections of ranibizumab. Other endpoints include mean change in central retinal thickness (CRT) and number of anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections received following administration of ABBV-RGX-314.

ABBV-RGX-314 has been well-tolerated across the 106 patients, with no treatment-related serious adverse events (AEs) reported. There were mild or moderate treatment-related AEs including conjunctival hemorrhage, increased intraocular pressure, episcleritis, and conjunctival hyperemia. Rates and severity of intraocular inflammation (IOI) increased between first and second dose levels in cohorts 1 and 2 and the third dose level in cohorts 4 and 5; these resolved with topical corticosteroids. There were no cases of IOI in the 21 patients that received dose level 3 in cohort 6 with a short course of prophylactic topical steroids.

READ MORE: REGENXBIO’s ABBV-RGX-314 Trials Aim to Reduce Treatment Burden in Inherited Retinal Diseases

“It should give us pause, that we could have the ability to reduce the treatment burden to our patients safely, which is phenomenal because we have had other drugs that have been administered by various other routes that have, unfortunately, caused severe inflammation. This seems to be well-tolerated in the suprachoroidal space," AAVIATE investigator David Boyer, MD, senior partner, Retina Vitreous Associates Medical Group, told CGTLive.

Investigators found that patients treated with ABBV-RGX-314 continued to demonstrate stable BCVA and CRT at 6 months, and anti-VEGF treatment burden was significantly reduced after administration of the therapy. The highest reduction was seen in dose level 3, in which patients had an 80% reduction in annualized injection rate and 50%remained injection-free.

"Real world evidence shows that patients with wet AMD are often undertreated due to the unsustainable treatment burden of frequent injections. As a result, many wet AMD patients experience significant vision loss over time," John Pitcher, MD, Eye Associates of New Mexico, said in a statement.1 "I am encouraged by the safety profile of ABBV-RGX-314 using suprachoroidal delivery and the potential of a one-time, in-office injection that can sustain constant anti-VEGF therapy to address a major unmet need for patients."

There are a number of investigational gene therapies in clinical trials for wet AMD. One early program, by Chengdu Origen Biotechnology and Vanotech, dosed the first patient with wet AMD in the ongoing phase 1 VAN-2201 clinical trial (NCT05657301) of the investigational gene therapy KH631 in November 2023.2 KH631 is designed to inhibit VEGF similarly to ABBV-RGX-314.

"I am excited to participate as a principal investigator in this important study. Dosing the first patient is an important milestone in the development of the single-administration gene therapy approach, which may hold promise to our patients in need of frequent treatment for their retinal diseases," Jeffrey S. Heier, MD, a principal investigator in the VAN-2201 trial and the director of the Vitreoretinal Service and of Retina Research at Ophthalmic Consultants of Boston, said in a statement.2

1. REGENXBIO Announces Positive Interim Data from Phase II AAVIATE® Trial of ABBV-RGX-314 for the Treatment of Wet AMD Using Suprachoroidal Delivery. News release. January 16, 2024.
2. Chengdu Origen and Vanotech Announce First Patient Dosed in VAN-2201 Phase 1 Trial of Gene Therapy for Wet Age-Related Macular Degeneration. News release. November 20, 2023. Accessed November 22, 2023.
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