Phase 2 LUNA Trial Results for Ixo-vec to Treat Neovascular AMD with Dante Pieramici, MD

At the 2025 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, Dante Pieramici, MD, codirector of the California Retina Research Foundation and assistant clinical professor of ophthalmology at the Doheny Eye Center in Southern California, presented the results of the Phase 2 LUNA trial of ixoberogene Soroparvovec (Ixo-vec) intravitreal gene therapy for the treatment of neovascular age-related macular degeneration (AMD).

The trial aimed to validate the efficacy and safety of a single injection ixo-vec in extending dosage intervals. Participants were randomized across two Ixo-vec doses, one of 6E10 and one of 2E11 vg/eye, which were given along with multiple corticosteroid prophylactic regimens including oral prednisone +/- topical difluprednate +/- IVT dexamethasone.1

“I think this is a big potential advantage,” Pieramici told HCPLive. Currently we use intravitreal injections, and even despite the newer anti-VEGF agents, patients generally need to have injections every 4-8, 12-16 weeks. It’s relatively frequent intravitreal injections and if they miss an injection, life gets in the way, they get hospitalized or something, then they get vision loss, and it may not come back. I think Ixo-vec potentially offers, at least for most patients…a potential one shot therapy.”

The study’s primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline to week 52. Secondary endpoints included the proportion of patients remaining aflibercept injection free, number of supplemental aflibercept injections overall, and mean change in central subfield thickness (CST).1

A total of 60 patients were enrolled with a mean age (standard deviation [SD]) of 76.6 +/- 7.8 years and a time since diagnosis of 3.0 +/- 2.9 years. These patients received 10.1 +/- 2.6 annualized anti-VEGF injections over the year leading up to receiving Ixo-vec. Baseline mean BCVA and CST were 72.3 (7.7) ETDRS letters and 350.6 (115.2) µm, respectively.1

By week 52, investigators noted maintenance of BCVA and CST with a least squares mean change of -2.1 (6E10) and -1.8 (2E11) ETDRS letters and -10.2µm (6E10) and -21.9µm (2E11), respectively. 54% of 6E10 recipients and 69% of 2E11 recipients received no aflibercept injections. 75% (6E10) and 79% (2E11) needed ≤1 supplemental aflibercept injection, while 89% (6E10) and 90% (2E11) needed ≤2 supplemental injections.1

After treatment, patients were surveyed about treatment preference. In total, 93% of patients preferred Ixo-vec over previous anti-VEGF therapy. Additionally, there were no serious treatment-related adverse events during the study. All adverse events related to Ixo-vec were mild or moderate.1

Pieramici and colleagues indicated that the results of LUNA highlighted the safety, efficacy, and tolerability of Ixo-vec in maintaining visual and anatomic endpoints over 52 weeks, with more than 50% of patients requiring no additional therapy.1

“I think it’s a very exciting time in gene therapy,” Pieramici said. “This is using it not to treat an inherited retinal disease, but using gene therapy as a biofactory approach as opposed to intravitreal injections. This, we’re hoping, is going to significantly reduce the treatment burden.”

Dante Pieramici, MD reports the following disclosures: Adverum, Eyepoint, Genentech, Inc., NGM Bio, Neurotech, Opthea, Perceive, Regeneron, Regenxbio, SMIR, Stealth, Unity: Code S (non-remunerative): None; Adverum, Gemini, Genentech, Inc., Iveric Bio, NGM Bio, Regeneron, Regenxbio: Code C (Consultant/Contractor): None; 4DMT, Adverum, Apellis, Chengdu Kanghong, Clearside, Eyepoint, F. Hoffmann-La Roche Ltd., Genentech, Inc., Iveric Bio, Jenssen, Kodiak Sciences, Novartis, Ocular Therapeutix, Ocurion, Opthea, Regeneron, Regenxbio, Resolute, Unity, Valo: Code F (Financial Support): None; Gemini: Code I (Personal Financial Interest): None

References

1. Pieramici, D, et al. Ixoberogene Soroparvovec (Ixo-vec) Intravitreal Gene Therapy for Neovascular Age-Related Macular Degeneration: Phase 2 LUNA 52-Week Data. Abstract presented at Association for Research in Vision and Ophthalmology in Salt Lake City, UT, from May 3 – May 8, 2025.