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Ixoberogene soroparvovec (Ixo-vec) intravitreal gene therapy for neovascular age-related macular degeneration (nAMD): LUNA trial 2-year results
Presenter:
Roger A. Goldberg, MD, MBA
Authors:
Roger A. Goldberg, MD, MBA1*; Dante J. Pieramici, MD, FASRS2; Paul Hahn, MD, PhD3; Charles C. Wykoff, MD, PhD4; Eduardo Uchiyama, MD5; Carl Regillo, MD, FACS6; Sean D. Adrean, MD7; Mark R. Barakat, MD8; Carl Danzig, MD9; Benjamin Bakall, MD, PhD10; David S. Boyer, MD11; Arshad M. Khanani, MD, MA12; Veeral Sheth, MD13; Bill Tan, PharmD14; Ashley Clark14, Traci Clemons, PhD14; Pauravi J. Gandhi, PhD14; Dina Akasheh, PhD14; Adam Turpcu, PhD14; Rabia G. Ozden, MD14; Star Seyedkazemi, PharmD14
1. Bay Area Retina Associates, 365 Lennon Ln. Suite 250 Walnut Creek, CA 94598
2. California Retina Consultants, Santa Barbara, CA, USA
3. Clara Maass Medical Center, Nanuet, NY, USA
4. Retina Consultants of Texas, Professor of Clinical Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, TX, USA
5. Broward Health Imperial Point, Retina Group of Florida, Fort Lauderdale, FL, USA
6. Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA
7. Retina Consultants of Orange County, Fullerton, CA, USA
8. Retina Macula Institute of Arizona, Scottsdale, AZ, USA
9. The Advanced Retina Institute, Bonita Springs, FL, USA
10. Associated Retina Consultants, Phoenix, AZ, USA
11. Retina-Vitreous Associates Medical Group, Beverly Hills, CA, USA
12. Sierra Eye Associates, Reno, NV, USA
13. University Retina and Macula Associates, IL, USA
14. Adverum Biotechnologies, Redwood City, CA, USA
Affiliation:
Intravitreal anti-VEGF agents effectively stabilize vision in most treatment-compliant nAMD patients. However, their limited durability requires frequent injections, and oscillations in anti-VEGF levels between injections can lead to fluctuations in retinal thickness, potentially increasing the risk of fibrosis and macular atrophy. Ixo-vec is an investigational intravitreal (IVT) gene therapy comprising an evolved AAV vector (AAV.7m8) carrying a transgene sequence that encodes aflibercept to enable sustained therapeutic levels. Here we report 2-year results from the LUNA Phase 2 clinical trial evaluating Ixo-vec in adults with nAMD.
LUNA is a multicenter, randomized, double-masked, parallel-group Phase 2 study evaluating Ixo-vec in treatment-experienced nAMD patients (NCT05536973). Eligible participants were randomized to Ixo-vec 6×1010 vg/eye (6E10) or 2×1011 vg/eye (2E11) and one of four prophylactic regimens: topical difluprednate ± IVT dexamethasone ± oral prednisone. The primary endpoints were safety and change from baseline in best corrected visual acuity (BCVA). Key secondary endpoints included change from baseline in central subfield thickness (CST) and the number of supplemental aflibercept injections.
A total of 60 participants were enrolled in the study (n=30 per dose group). Baseline characteristics are summarized in Table 1. The mean annualized anti-VEGF injection rate in the year prior to enrollment was 10.1, reflecting a high-need population. At Week 104, the least squares (LS) mean change in BCVA was +0.5 and ‒2.3 ETDRS letters in the 6E10 and 2E11 groups, respectively. The LS mean change in CST was 9.8 µm and ‒14.8 µm, respectively. At year 2, the mean annualized injection rate was 1.1 in the 6E10 group and 0.9 in the 2E11 group, reflecting cumulative reductions of 89% and 90%, respectively, compared to the 12 months prior to enrollment. All Ixo-vec–related adverse events were mild or moderate.
Administration of a single IVT injection of Ixo-vec to individuals with nAMD and a high injection burden was well tolerated and resulted in stable BCVA and CST and a marked and sustained reduction in injection burden through 2 years. A Phase 3 trial evaluating Ixo-vec in individuals with nAMD is underway (ARTEMIS, NCT06856577).