Gene Therapy for Wet AMD Reduces Need for Anti-VEGF Injections | ASRS 2024

A gene therapy to treat patients with wet age-related macular degeneration reduced the need in annualized anti-vascular endothelial growth factor (VEGF) injections in 90% of patients in a phase 2 trial, according to data presented at the American Society of Retina Specialists 2024 meeting in Stockholm.

Charles C. Wykoff, M.D., Ph.D., board-certified Medical and Surgical Retina Specialist and ophthalmologist with Retina Consultants of Texas, presented data from the interim 26-week data the ongoing LUNA phase 2 study of ixoberogene soroparvovec (Ixo-vec) to treat patients with wet age-related macular degeneration.

Wet AMD is an advanced form of the disease that can cause rapid and severe vision loss. About 20 million people in the United States have some form of AMD, and of those, about 1.5 million have late-stage AMD, which includes wet AMD.

Developed by Adverum Biotechnologies, ixo-vec is a propriety vector capsid, AAV.7m8, carrying an aflibercept coding sequence. Aflibercept inhibits VEGF and is the active ingredient in Regeneron’s Eylea, which is approved to treat patients with wet AMD, diabetic macular edema and diabetic retinopathy.

At week 26 of the LUNA trial, 115 patients were treated with either the 2E11 or 6E10 dose of ixo-vec. Patients who received the 2E11 dose had a mean 94% reduction in annualized anti-VEGF injections, and 85% received no supplemental injections. Those who received the 6E10 doses had mean 90% reductions in annualized anti-VEGF injections, and 68% of patients at received no supplemental injections through 26 weeks.

The dosages used for LUNA were based on the results of the phase 1 OPTIC trial, which enrolled 30 patients with wet AMD treated with 2E11 dose. In the study, patients had an 84% reduction in annualized anti-VEGF inductions.

“We saw very good efficacy [in the OPTIC trial], but there was interocular inflammation,” Wykoff said in an interview before the meeting. “The goal of LUNA was to aim for lower viral doses, and that why the newer lower concentration of 6E10 was included.”

The intraocular inflammation responsive to local corticosteroids.

But Wykoff indicated it may be too early to determine which dose of ixo-vec will be used for a phase 3 trial.