Adverum Biotechnologies reported 52-week results from its Phase 2 LUNA trial, evaluating ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022), a gene therapy for neovascular (“wet”) age-related macular degeneration (nAMD). The data indicate significant reductions in treatment burden, sustained visual outcomes, and a favorable safety profile, the company said in a press release.

Ixo-vec utilizes a proprietary vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette. Unlike other ophthalmic gene therapies that require surgery for subretinal administration, Ixo-vec is delivered as a one-time intravitreal injection in the physician’s office, the company said. 

In the LUNA study (NCT05536973), which included 60 patients across two dose cohorts, Ixo-vec reduced the need for anti-VEGF injections by 88% to 92% compared to baseline. More than half of participants were injection-free through one year, with 6E10 vg/eye and 2E11 vg/eye doses achieving injection-free rates of 54% and 69%, respectively. Additionally, visual acuity and retinal thickness metrics remained stable, indicating maintained efficacy.

The trial tested different prophylactic regimens, including topical steroid eyedrops. No inflammation was reported in patients on the 6E10 dose with topical steroids alone at 52 weeks. Adverse events were mild or moderate and resolved with local treatment.

The company also reported 4-year data from the OPTIC study (NCT03748784), with participants experiencing an 86% reduction in their annualized need for anti-VEGF injections compared to baseline. Nearly half of the participants remained entirely injection-free throughout the study period. Additionally, 78% of those who were injection-free after the first year maintained this status through year 4, indicating sustained efficacy. Aflibercept protein levels were observed up to five years after treatment, further demonstrating Ixo-vec’s durability.

Adverum Biotechnologies is using data from the LUNA and OPTIC trials to design and optimize its Phase 3 pivotal program for Ixo-vec, the company reported. The 6E10 dose, along with the topical steroid prophylaxis regimen, will be the focus of these studies. The ARTEMIS Phase 3 study, expected to begin in the first half of 2025, will enroll 284 patients in a double-masked, randomized trial to compare Ixo-vec to the current standard of care, aflibercept 2 mg (Eylea; Regeneron). This study will measure noninferiority in visual acuity improvements over 52 weeks and evaluate Ixo-vec’s ability to reduce treatment burden.

The FDA has granted Ixo-vec fast track designation as a treatment for nAMD.