The first neovascular AMD session focused on emerging therapies for wet AMD, with a strong emphasis on gene therapy aimed at reducing treatment burden while maintaining visual and anatomic outcomes.
The first presentation by Dr. Brian Joondeph reviewed long-term results from the Phase I OPTIC trial evaluating intravitreal Ixo-vec, a gene therapy designed to enable sustained intraocular production of aflibercept. This study enrolled heavily pretreated patients with high injection burden, averaging approximately 10 injections in the year prior to enrollment. A single intravitreal injection of Ixo-vec resulted in sustained intraocular aflibercept expression for up to five years. Visual acuity and OCT outcomes remained stable through four years, while treatment burden was dramatically reduced. Patients experienced an approximately 85% reduction in annualized injection frequency, decreasing from about 10 injections per year pre-treatment to roughly 1.5 afterward, with approximately half of patients remaining injection-free at four years. Safety findings were favorable, with no treatment-related serious ocular adverse events such as vasculitis, retinitis, or vascular occlusion. Inflammation was observed in a dose-dependent manner but was responsive to corticosteroids and resolved within one year.
Next, Dr. Carl Regillo presented the Phase II LUNA trial which further evaluated Ixo-vec. This study included 60 previously treated nAMD patients with a previously high treatment burden. Over two years, both investigative dose levels demonstrated stable visual acuity and retinal thickness, with substantial reductions in supplemental anti-VEGF injections. Approximately 46 – 61% of patients required one or no rescue injections over two years, and treatment burden decreased by about 90% compared to pre-enrollment levels. Notably, the median time to first supplemental injection extended to 65 – 94 weeks, suggesting meaningful durability. Safety outcomes remained consistent with earlier findings, with no Ixo-vec-related serious adverse events and no cases of vasculitis or occlusive disease. Inflammatory events were generally mild and manageable with corticosteroids.
Dr. Gregg Kokame then presented on the ABBV-RGX-314 Sura-Vec Phase II pharmacodynamic study. This study utilized a subretinal AAV8 vector to deliver a gene encoding an anti-VEGF fragment. The primary endpoint was protein expression at six months and was successfully achieved, with consistent levels across both high and low dose arms as well as across two manufacturing platforms. Patients in this study were also heavily pretreated, with 21 – 26 prior injections. At one year, both visual and anatomic outcomes improved, and there was a marked reduction in injection burden, with many patients requiring no supplemental injections. Safety findings were consistent with expectations following subretinal surgery, with no major unexpected adverse events reported.
Beyond gene therapy, Dr. Dean Eliott presented a first-in-human Phase I study evaluated TH-103, a next-generation biologic designed to enhance VEGF inhibition. In treatment-naĂŻve patients, a single dose resulted in rapid and meaningful improvements in both visual acuity and retinal thickness. No serious adverse events or dose-limiting toxicities were observed. Mild to moderate intraocular inflammation occurred in two patients but was attributed to manufacturing factors and resolved after process improvements. Early signals suggested potential durability, with a subset of patients maintaining disease control beyond four to six months after a single injection.
Dr. David Brown presented findings on another novel agent, Tiespectus (MK-8748), a bispecific molecule targeting VEGF and activating the Tie2 pathway. Tiespectus demonstrated promising early results in a Phase I/2A study. Patients showed robust improvements in visual acuity and retinal anatomy, with approximately 8 letter gains at 12 weeks and near-complete resolution of fluid. The therapy was well tolerated, with no drug-related serious adverse events reported.
Finally, Dr. Rishi Singh presented results from the DAVIO 2 Phase II trial which evaluated EYP-1901, a sustained-delivery intravitreal insert targeting VEGF, PDGF, and IL-6 pathways. In previously treated patients, a single dose maintained visual acuity in 85% of patients, with outcomes comparable to Q8 week aflibercept. Importantly, no patients experienced significant vision loss (≥15 letters), and safety findings were favorable, with no serious ocular or systemic adverse events.
Overall, these studies highlighted a shift toward longer acting and potentially one-time treatments for nAMD. Gene therapies such as Ixo-vec and Sura-Vec demonstrate the potential to dramatically reduce injection burden while maintaining efficacy, and emerging biologics and sustained-delivery systems further expand the therapeutic landscape. Safety profiles across these approaches remain encouraging, though long-term effects, particularly with sustained VEGF suppression, remain an area of ongoing investigation.
