Data presented at the ASGCT 2023 Annual Meeting supports that Adverum’s Ixo-vec allows for lower dose administration with improved inflammation profile.
Adverum Biotechnologies shared new nonclinical data supporting the use of ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022). Ixo-vec is currently being evaluated in the phase 2 LUNA trial for the treatment of wet age-related macular degeneration (wet AMD).
The data was presented at the American Society of Gene & Cell Therapy (ASGCT) 2023 Annual Meeting in Los Angeles, California during an oral presentation on the identification of dose-dependent immune landscape signatures in nonhuman primates (NHPs), an oral presentation of nonclinical data that supports the potential for staggered, bilateral dosing of Ixo-vec, and a poster presentation evaluating Ixo-vec per cell vector genome (vg) biodistribution and mRNA expression in NHPs.
“Our nonclinical data presented at ASGCT support the use of the human equivalent doses 2x10^11 vg/eye and 6x10^10 vg/eye doses being evaluated in the LUNA trial,” stated Brigit Riley, Ph.D., chief scientific officer at Adverum in the press release. “It is well understood that gene therapy products cause dose-dependent inflammation regardless of serotype and route of administration. We were pleased to see that the Ixo-vec doses advanced in the LUNA trial can achieve therapeutic aflibercept levels in NHPs that improve the inflammation profile. These data support our development efforts around lower dose administration of Ixo-vec and enhanced prophylactic corticosteroid regimens being evaluated in LUNA. We look forward to sharing interim 14-week aflibercept protein levels for a percentage of the cohort in the LUNA trial in the third quarter of this year.”
The ASGCT poster and oral presentations will be made available on the Publications page of the Adverum website.
Adverum is developing ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022), its clinical-stage gene therapy product candidate, for the treatment of wet AMD. 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 to administer the gene therapy under the retina (sub-retinal approach), Ixo-vec is designed to be administered as a one-time IVT injection in the physician’s office, deliver long-term efficacy, reduce the burden of frequent anti-vascular endothelial growth factor (VEGF) injections, optimize patient compliance and improve vision outcomes for patients with wet AMD. In recognition of the need for new treatment options for wet AMD, the U.S. Food and Drug Administration granted Fast Track designation for Ixo-vec for the treatment of wet AMD. Ixo-vec also received PRIME designation from the European Medicines Agency and the Innovation Passport from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency for the treatment of wet AMD.
The LUNA trial is a double-masked, randomized, Phase 2 trial being conducted at approximately 40 sites in the U.S. and Europe. LUNA will evaluate Ixo-vec in subjects with wet AMD who are 50 years or older and have demonstrated a response to anti-VEGF treatment. Up to 72 subjects will be randomized equally between the previously evaluated 2E11 vg/eye dose and a new, lower 6E10 vg/eye dose. Four prophylactic corticosteroid regimens will be studied with the aim of establishing a prophylactic corticosteroid regimen with minimal need for inflammation management post prophylaxis. Prophylactic regimens being evaluated include 22 weeks of a tapered regimen of topical difluprednate (Durezol®), a single administration of IVT dexamethasone (Ozurdex®), and a combination of either topical Durezol® or IVT Ozurdex® with up to 10 weeks of a tapered regimen of oral prednisone. All four prophylactic corticosteroid regimens in LUNA cover the period of peak immunogenicity observed in non-clinical studies and in the Phase 1 OPTIC study.
The LUNA trial primary endpoints are mean change in best corrected visual acuity (BCVA) from baseline to one year, as well as the incidence and severity of adverse events. Important secondary endpoints in LUNA include the mean change in central subfield thickness (CST) from baseline to one year and assessing the effectiveness of prophylactic corticosteroid regimens on minimizing inflammation. Additionally, LUNA will assess aflibercept protein levels starting at Week 14 and include an interim analysis at Week 26. Study participants will have the option to enroll in a long-term extension study.
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