OPTIC and LUNA Suggest Long-Term Efficacy of Ixo-Vec in nAMD, with Sean Adrean, MD

Results from the OPTIC and LUNA trials have indicated the safety and efficacy of Ixo-vec in maintaining visual and anatomic endpoints in patients with neovascular age-related macular degeneration (nAMD) and reducing injection burden in patients who previously required frequent anti-VEGF injections.1

Presented at the 43rd Annual Scientific Meeting of the American Society of Retina Specialists in Long Beach, CA, these data were compiled from the 5-year OPTIC trial (2 years plus a 3-year extension) and the 52-week LUNA phase 2 study. Both were conducted on patients with nAMD who demonstrated a response to anti-VEGF therapy.1

The gene therapy Ixo-vec is comprised of the AAV.7m8 capsid, which is in turn derived from in vivo directed evolution for enhanced transduction of retinal cells. It provides sustained aflibercept expression after a single intravitreal injection.1

OPTIC evaluated the safety and durability of Ixo-vec at doses of 6e11 vg/eye and 2e11 vg/eye. Patients with nAMD and a high anti-VEGF treatment burden received 1 injection of Ixo-vec at 2e11 accompanied by a short course of steroid prophylaxis (13 days of prednisone or 6 weeks of difluprednate). A total of 15 patients received the 2e11 dose; this group had a mean (standard deviation [SD]) age of 78.4 (7.4) years and time (SD) since diagnosis of 3.6 (2.5) years.1

At baseline, patients in OPTIC had received a mean (SD) of 9.9 (1.3) annualized anti-VEGF injections during the year prior to Ixo-vec; they had a mean (SD) best-corrected visual acuity (BCVA) and central subfield thickness (CST) of 65.4 (7.4) ETDRS letters and 407.1 (172.5) µm, respectively. During the study, patients experienced an 87% reduction in annualized injection burden. A total of 47% of patients remained anti-VEGF injection-free over 4 years.1

Additionally, Ixo-vec maintained a mean BCVA change of -2.9 ETDRS letters and mean CST improvement of -117.7 µm from baseline through 4 years. Early aqueous AFL levels were associated with sustained protein expression. Patients saw no new onset of inflammation after week 28, and all patients were inflammation-free at 1 year.1

The LUNA trial, a multicenter, randomized, double-masked study, compared 60 patients who had been randomized to either the low dose from OPTIC (2e11) or a new lower dose of 6e10 vg/eye with enhanced steroid prophylaxis. This included locally administered options of a 22-week regimen of difluprednate drops or intravitreal dexamethasone followed by difluprednate drops.1

Patients in LUNA had a mean time since diagnosis of 3 (2.9) years and had received 10.1 annualized anti-VEGF injections in the year prior to receiving Ixo-vec. Baseline BCVA and CST were 27.3 (7.7) ETDRS letters and 350.6 (115.2) µm, respectively. Previously treated patients showed a significant reduction of treatment burden, with 54% (6e10) and 69% (2e11) patients remaining injection-free at week 52. 75% (6e10) and 79% (2e11) needed ≤1 supplemental aflibercept injection, while 89% (6e10) and 90% (2e11) needed ≤2.1

LUNA saw a BCVA change of -2.1 (6e10) and -1.8 (2e11) ETDRS letters and a CST change of -10.2 µm (6e10) and -21.9 µm (2e11). There were no Ixo-vec-related serious adverse events.1

HCPLive met with lead presenter Sean Adrean, MD, to discuss the findings of these studies and their implications for the future of genetic treatment in ophthalmology. He commented first on the notable – although clinically insignificant – reduction in BCVA in these trials.

“Most times, over time as you’re looking at how patients do, there is a reduction in vision slowly over time, and that’s been seen across multiple clinical trials,” Adrean told HCPLive. “Patients will start developing geographic atrophy, some patients will have subretinal fibrosis, and these things can certainly limit the visual outcomes over time. So, seeing a slight decline in vision is not unexpected.”

Adrean also spoke to his optimism about these data and his hopes for genetic therapy in ophthalmology in the future.

“Anytime there’s genetic therapy involved, there are definitely different aspects of regulatory bodies that are monitoring these and seeing how these patients do,” Adrean said. “By the time these things come to market, hopefully that will be solved. I think patients will be excited about having the opportunity to have fewer injections, and I think genetic therapy in general doesn’t sound as concerning as some other therapies like stem cells or things like that.”

Editor's Note: Adrean reports disclosures with Genentech, Adverum, and Opthea.

References

1. Adrean S, Boyer D, Regillo C, et al. Ixoberogene Soroparvovec (Ixo-vec) Intravitreal Gene Therapy for Neovascular Age-Related Macular Degeneration (nAMD): Results From OPTIC and LUNA Trials. Presented at the 43rd Annual Scientific Meeting of the American Society of Retina Specialists in Long Beach, CA, July 30-August 2, 2025.