REGENXBIO’s ABBV-RGX-314 Reduces Need for AntiVEGF Injections After Application in Fellow Eyes of Patients With Wet AMD
The data comes from a phase 2 substudy (NCT03999801) that treated the fellow eyes of patients who had previously been treated with ABBV-RGX-314.
Arshad Khanani, MD
Credit: Sierra Eye Associates
REGENXBIO’s ABBV-RGX-314, an investigational adeno-associated virus (NAV AAV8) vector-based gene therapy intended to treat wet age-related macular degeneration (wet AMD), has reduced the need for standard of care antiVEGF injections in patients with bilateral wet AMD who received treatment with the gene therapy in their fellow eye after previous treatment in an initial eye.1
The data comes from a phase 2 substudy (NCT03999801) that treated the fellow eyes of patients who had previously been treated with ABBV-RGX-314 in their “study eye” in a parent study. In the substudy, ABBV-RGX-314 was administered to patients subretinally at a dose of 1.3x1011 GC/eye about 1 year or more after they had received the gene therapy in their study eye. The findings were presented at the American Academy of Ophthalmology (AAO) 2024 meeting, held in Chicago, Illinois, October 18 to 21.
Among 9 patients who had 9 months of follow-up after treatment in the fellow eye, a 97% decrease in annualized antiVEGF treatment burden was recorded. Furthermore, 78% of the patients were completely free of antiVEGF injections after receiving the gene therapy, and none of the patients needed more than 1 supplemental antiVEGF injection during the 9 month timeframe. REGENXBIO additionally pointed out that best-corrected visual acuity and central retinal thickness were sustained at 9 months posttreatment. The company also stated that aqueous protein was produced at similar levels in both of patients’ treated eyes.
"The majority of our patients with wet AMD eventually have bilateral disease and face a substantial treatment burden with frequent lifelong injections in both eyes,” Arshad Khanani, MD, the director of clinical research and director of Fellowship at Sierra Eye Associates, said in a statement.1 “This leads to suboptimal real-world vision outcomes with current standard of care. The fellow eye dosing data with ABBV-RGX-314 is a milestone for the field of gene therapy for common retinal diseases, as this is the first time we have performed bilateral treatment for wet AMD patients. These results, combined with the durable treatment effect up to 4 years shown in long-term follow up, highlight the potential of ABBV-RGX-314 as a one-time effective treatment option for patients with wet AMD."
In terms of safety, ABBV-RGX-314 was characterized as “well-tolerated” in the fellow eyes. No serious adverse events (AEs) deemed related to the gene therapy product were reported. Mild retinal pigmentary changes occurring in periphery and postoperative conjunctival hemorrhage were noted to be common AEs, but all of these resolved within days or within weeks. REGENXBIO stated that outside of prophylactic steroids typically used in vitrectomy surgery, no additional prophylactic steroids were used in the substudy.
"The results presented at AAO from the phase 2 substudy, the first to evaluate a gene therapy in fellow eyes for wet AMD, demonstrate that ABBV-RGX-314 could be a treatment for patients with bilateral disease and add to the already-robust data demonstrating ABBV-RGX-314's potential to impact the treatment paradigm for patients with wet AMD," Curran Simpson, the president and chief executive officer of REGENXBIO, added to the statement.1 "With more treated patients and the longest-term data of any gene therapy program for wet AMD, REGENXBIO, with our partner AbbVie, are well-positioned to bring the first gene therapy to market with the hope of preserving long-term vision for millions of patients globally with wet AMD."
Notably, ABBV-RGX-314 is not the only gene therapy product in development for wet AMD. 4D Molecular Therapeutics is evaluating 4D-150, an investigational dual-mechanism gene therapy for wet AMD in the phase 1/2 PRISM clinical trial (NCT05197270).2 Data from this trial were announced in July 2024. At 24 weeks posttreatment, a landmark analysis was conducted and the 30 patients who received the planned phase 3 dose showed a mean decrease of 89% in annualized injection rate of antiVEGF injections. Furthermore, 93% of these patients received 0 or only 1 antiVEGF injection after treatment with the gene therapy and 77% were entirely free of antiVEGF injections.
Another gene therapy in development for wet AMD is Adverum Biotechnologies’ ixoberogene soroparvovec (ixo-vec).3 Notably, ixo-vec recently received regenerative medicine advanced therapy designation from the FDA in August 2024.
