The phase 3 development program for ixoberogene soroparvovec (ixo-vec; Adverum Biotechnologies) in neovascular age-related macular degeneration (nAMD) is moving forward, according to Deepak Sambhara, MD, FASRS, who presented an overview of the program at the 2026 Retina World Congress.
Ixo-vec is designed as a clinic-based intravitreal gene therapy using an AAV7m8 vector engineered to cross the internal limiting membrane and transduce retinal cells. The therapy aims to enable continuous intraocular aflibercept production after a single injection, leading to durable suppression of choroidal neovascularization. The registration studies ARTEMIS and AQUARIUS will evaluate whether a single injection of ixo-vec can provide sustained aflibercept expression and reduce treatment burden in both treatment-naïve and treatment-experienced patients with nAMD.
“ARTEMIS and AQUARIUS are undergoing evaluation right now, with ARTEMIS being fully enrolled and AQUARIUS having begun enrollment at the tail end of last year,” explained Dr. Sambhara, a partner and medical director of research at the Eye Clinic of Wisconsin in Wausau, Wisconsin.
According to Dr. Sambhara, the goal is to address a persistent limitation of current anti-VEGF therapy: the variability associated with intermittent dosing. He pointed to evidence linking fluctuations in retinal thickness with poorer long-term outcomes, including fibrosis and atrophy. “The more variability there is, the worse your vision does over time,” he said. “And it doubles that risk of fibrosis and atrophy.”
Dr. Sambhara also cited survey data suggesting strong physician interest in more durable therapies. “Sixty-five percent of physicians identify greater durability as the largest unmet need for nAMD,” he said, adding that many retina specialists view gene therapy as a potential long-term solution.
The current phase 3 studies were informed primarily by findings from the phase 1 OPTIC trial and the phase 2 LUNA study, both of which enrolled nAMD patients with high treatment burden. In OPTIC, patients had received an average of approximately 10 anti-VEGF injections during the year before enrollment. “These were the frequent flyers in our clinics,” Dr. Sambhara said. “If our clinics were an ice cream social where the 10th injection would be free, these patients would have had their punch cards all punched.”
OPTIC enrolled 30 patients and included long-term extension follow-up, while LUNA enrolled approximately 60 patients. Both studies evaluated visual acuity, central subfield thickness (CST), supplemental injection requirements, and safety.
One of the key findings from OPTIC was the persistence of measurable aflibercept expression years after treatment. According to Dr. Sambhara, aqueous humor analyses demonstrated detectable aflibercept levels 4 to 5 years after a single administration. The study also suggested sustained anatomic control with reduced treatment burden. In OPTIC, patients who had previously required injections approximately every 5 weeks averaged fewer than 2 injections annually after treatment. Best-corrected visual acuity and CST remained stable during follow-up. “We don’t expect to see vision bumping up,” Dr. Sambhara said of the heavily pretreated cohort. “But the important thing here is we see visual acuity stability through OPTIC and OPTIC extension.”
LUNA produced similar findings. Across both dose groups, visual acuity remained stable and CST curves showed limited fluctuation over time. “We’re not seeing the zigzag or sawtoothing patterns that we’re used to seeing with bolus intravitreal anti-VEGF injections,” Dr. Sambhara said. “We’re seeing constant flat line of CST.”
Investigators also reported substantial reductions in supplemental treatment requirements. In LUNA, treatment burden declined by nearly 90% during the first 2 years of follow-up, and many patients went more than a year before requiring additional anti-VEGF therapy.
Safety findings from OPTIC and LUNA helped determine the dose and prophylactic steroid regimen now being used in phase 3. According to Dr. Sambhara, no cases of retinal vasculitis, retinitis, choroiditis, vascular occlusion, or hypotony were observed in either study. Inflammation events were generally mild or moderate and responded to local corticosteroids. “The phase 3 dose, which is the 6E10 vg, the lower dose used in LUNA, along with local prophylaxis, led to no inflammation that was new after week 30,” he said.
The company has reported that it expects data from ARTEMIS in early 2027, followed by AQUARIUS later in the year. RP