Adverum Biotechnologies’ multicenter, double-masked LUNA trial will enroll 72 patients aged 50 years or older.
The first patient has been dosed in a phase 2 clinical trial (NCT05536973) of Adverum Biotechnologies’ ixoberogene soroparvovec (ixo-vec, ADVM-022), an investigational gene therapy intended for the treatment of wet age-related macular degeneration (wet AMD).
Ixo-vec uses AAV.7m8, a proprietary vector capsid, and is administered in a single-dose via intravitreal (IVT) injection. It was previously granted PRIME designation by the European Medicines Agency in June 2022. In the earlier phase 1 OPTIC trial (NCT03748784), ixo-vec was shown to produce sustained aflibercept expression and improve visual outcomes for patients with wet AMD, and was well-tolerated. Ixo-vec was also previously investigated in a phase 2 clinical trial (INFINITY; NCT04418427) for diabetic macular edema (DME). However, the trial was halted after a serious dose-limiting toxicity was observed, resulting in Adverum no longer pursuing ixo-vec for that indication.
“Dosing the first subject in the Phase 2 LUNA study brings us a step closer to our mission of establishing gene therapy as a new standard of care for some of the leading causes of vision loss,” Richard Beckman, MD, chief medical officer, Adverum Biotechnologies, said in a statement. “The trial is designed to assess the safety and efficacy of 2 dose levels of a single, in-office intravitreal injection of Ixo-vec for the treatment of wet AMD. We are excited that LUNA will allow us to explore a new, lower 6x1010 dose that we hope will build on the robust, durable efficacy and safety profile already demonstrated with the 2x1011 dose in the OPTIC trial.”
The multicenter, double-masked LUNA trial will enroll 72 patients aged 50 years or older. Participants are required to have had a meaningful response to anti-vascular endothelial growth factor (VEGF) injections and must be actively receiving anti-VEGF treatment with a minimum of 2 injections within the 4 months prior to screening. Participants must additionally show evidence of active primary or recurrent sub-foveal choroidal neovascularization (CNV) and have a best corrected visual acuity (BCVA) early treatment diabetic retinopathy study (ETDRS) Snellen equivalent between 20/32 and 20/320 (inclusive). Patients who have a history of retinal detachment or retinal pigment epithelium rip or tear, patients who have uncontrolled diabetes, HbA1c 7% or greater, or patients who have ocular or periocular infection or intraocular inflammation in either eye within 1 month prior to the randomization visit will be excluded. Additional exclusion criteria relate to other current and past health conditions and treatment history.
Participants will be randomly assigned to either the lower dose arm or the higher dose arm and will receive a single IVT injection of ixo-vec in 1 eye in combination with 1 of 4 corticosteroid treatment regimens: either topical difluprednate (Durezol), IVT dexamethasone (Ozurdex), a combination of topical Durezol with oral prednisone, or a combination of IVT Ozurdex with oral prednisone. The study aims to determine the ideal prophylactic regimen and dose pairing for minimization of inflammation. Primary end points include incidence and severity of ocular and non-ocular adverse events and the mean change in BCVA from baseline. Secondary end points include the percent of participants who lose or gain at least 5, 10, or 15 letters in BCVA; the percent of patients who do not require supplemental aflibercept injections; the percentage reduction of anti-VEGF injections; the mean change in central subfield thickness (CST) from baseline; and the percentage of participants without CST fluctuations greater than 50 μm. The study is recruiting at approximately 40 sites in the United States and the trial is estimated to be completed in February 2024. The company expects initial data to be reported in 2023, including Week 10 aflibercept protein expression and a Week 26 interim analysis.
“As a principal investigator in LUNA, I am excited at the potential of Ixo-vec to meaningfully reduce the treatment burden of frequent anti-VEGF injections for wet AMD patients,” Sean Adrean MD, partner, Retina Consultants of Orange County, added to the statement. “I’m intrigued by the efficacy profile seen in the OPTIC trial, where a single intravitreal injection of Ixo-vec demonstrated 3 years of stable aflibercept expression to date, as well as maintenance of vision and improved anatomical outcomes. I look forward to studying the potential of Ixo-vec to offer a safe and efficacious, and potentially transformational, intravitreal treatment option for my patients with wet AMD.”