ASRS 2026: Ixo-vec gene therapy sustains reduced anti-VEGF burden at 5 years in wet AMD

A single injection with durable anti-VEGF expression

A single intravitreal injection of ixoberogene soroparvovec (Ixo-vec; Adverum Biotechnologies) sustained aflibercept expression and reduced anti-VEGF treatment burden through 5 years in patients with neovascular age-related macular degeneration (nAMD), according to long-term extension results from the phase 1 OPTIC trial (NCT04645212) presented at the American Society of Retina Specialists (ASRS) 2026 annual meeting by Szilárd Kiss, MD, FASRS.

OPTIC evaluated Ixo-vec, an anti-VEGF gene therapy that uses an evolved adeno-associated viral vector to turn the eye into what Kiss described as a "biofactory" producing aflibercept, a clinically validated recombinant anti-VEGF protein. Rather than episodic dosing, the approach aims to control disease activity after one injection. "It's episodic treatment, like running on a treadmill," Kiss told Modern Retina, characterizing the current standard of care.

Five-year efficacy and safety in a high-need population

The trial enrolled a heavily treated population: participants had received a mean of 9.9 annualized anti-VEGF injections in the prior 12 months. Among the 15 patients who received the 2×10¹¹ vg/eye dose, evaluation at 5 years showed an 87% cumulative reduction in mean annualized anti-VEGF injections compared with the year before enrollment. The mean change in best-corrected visual acuity from baseline to year 5 was –6.1 ETDRS letters (90% CI, –15.9 to 3.7), and the mean change in central subfield thickness was –131.6 µm (90% CI, –244.0 to –19.2). Investigators observed sustained aqueous aflibercept levels through year 5.¹

Kiss emphasized that the population shapes interpretation, as this was a hypothesis-generating phase 1 study in treatment-experienced patients. Ixo-vec was generally well tolerated, with no hypotony, vasculitis, retinitis, choroiditis, or vascular occlusion. All participants were inflammation free at 1 year; apart from one participant whose inflammation was first reported at 2.5 years following cataract surgery, all remained inflammation free through 5 years.¹

Two phase 3 trials—ARTEMIS (NCT06856577) and AQUARIUS (NCT07482176)—are enrolling both treatment-naïve and treatment-experienced patients and comparing Ixo-vec with aflibercept dosed every 8 weeks.¹

Reference
1. Kiss S. Ixoberogene soroparvovec intravitreal gene therapy for neovascular age-related macular degeneration: 5-year results from the OPTIC long-term extension trial. Presented at: American Society of Retina Specialists 44th Annual Meeting; July 15-18, 2026; Montréal, Québec, Canada.