Adverum Biotechnologies' ixoberogene soroparvovec (Ixo-vec) gene therapy has demonstrated promising long-term benefits for patients with neovascular (wet) age-related macular degeneration (nAMD), according to the 52-week results from the LUNA Phase 2 trial and 4-year follow-up data from the OPTIC first-in-human trial. The data, announced on November 18, 2024, highlight the potential of Ixo-vec to reduce injection burden and maintain visual and anatomic endpoints in nAMD patients.
LUNA Trial Results
The LUNA trial is a double-masked, randomized Phase 2 study involving 60 nAMD patients randomized into two dose cohorts: 6E10 or 2E11 vg/eye. The primary goal of LUNA is to determine the optimal dose and prophylactic regimen of Ixo-vec for Phase 3 registrational trials. Baseline data indicated that patients required an average of 10.1 anti-VEGF injections in the year before enrollment.
At 52 weeks, both doses of Ixo-vec maintained visual and anatomic endpoints. The least-squares mean best-corrected visual acuity (BCVA) change from baseline to Week 52 was -2.1 letters (95% CI, -4.8 to 0.7) and -1.8 letters (95% CI, -4.6 to 0.9) for the 6E10 and 2E11 doses, respectively. Anatomic outcomes at Week 52 showed the least-squares mean change in central subfield thickness (CST) was -10.2 μm (95% CI, -29.0 to 8.5) and -21.9 μm (95% CI, -40.4 to -3.3) in the 6E10 and 2E11 doses, respectively.
Notably, both the 6E10 and 2E11 doses achieved significant reductions in treatment burden (88% and 92%, respectively) and increased the proportion of patients who were injection-free (54% and 69%, respectively) through 52 weeks. Importantly, no patients in the 6E10 dose group with topical eyedrops experienced inflammation at Week 52 or any subsequent visit.
OPTIC Trial Results
The OPTIC trial is an ongoing, open-label, dose-ranging first-in-human trial that enrolled 30 patients with nAMD who were receiving frequent intravitreal injections (mean, 9.9 injections). Patients were administered one of two Ixo-vec doses: 2E11 or 6E11, along with either 6 weeks of prophylactic topical steroid eye drops or 13 days of prophylactic oral steroids. The study was initially set for 2 years, with an optional 3-year extension.
After 4 years of follow-up, data showed an 86% reduction in annualized anti-VEGF injections, demonstrating a substantial reduction in treatment burden. Approximately 50% of patients remained injection-free throughout the 4-year period. Ixo-vec was generally well-tolerated, with a favorable safety profile.
Path to Phase 3
Based on these positive results, Adverum has selected the 6E10 Ixo-vec dose with topical steroid prophylaxis to advance into a pivotal program consisting of two double-masked, randomized Phase 3 studies. The ARTEMIS study, planned to initiate in the first half of 2025 in the US, will be a non-inferiority study comparing Ixo-vec to aflibercept 2 mg administered every 8 weeks in a broad nAMD patient population, including both treatment-naive and experienced patients. The primary endpoint, measured at an average of Weeks 52 and 56, is the non-inferiority change in mean BCVA from baseline, with a non-inferiority margin of -4.5 letters. The trial design incorporates feedback from the FDA.
