Nonclinical study of ixo-vec gene therapy for nAMD supports efficacy for a human dose of 6E10 vg/eye and staggered dosing of fellow eyes. Academic Article uri icon

Overview

abstract

  • Ixoberogene soroparvovec (ixo-vec), formerly ADVM-022, is an adeno-associated virus (AAV) gene therapy using the AAV.7m8 capsid for intravitreal delivery (IVT) to transduce retinal tissue and produce sustained intraocular aflibercept for treating neovascular age-related macular degeneration (nAMD). Non-clinical studies show that aflibercept production by ixo-vec is less than dose proportional, while intraocular inflammation (IOI) increases with dose, suggesting that lower doses could yield effective aflibercept levels with reduced IOI risk. Our evaluation confirmed that doses as low as 3E10 vg (vector genome)/eye (6E10 vg/eye human equivalent) maintained effective aflibercept production. The concept behind ADVM-022 is supported by clinical studies OPTIC (NCT03748784) and LUNA (NCT05536973), where a single IVT administration eliminated or significantly reduced the need for additional anti-VEGF injections in patients. Moreover, LUNA confirmed the clinical efficacy of a 6E10-vg/eye dose, demonstrating robust and sustained aflibercept levels. Additionally, we evaluated staggered dosing in contralateral eyes to treat asynchronous disease development. Staggered dosing, administered 2 months apart, did not exacerbate IOI, and both eyes maintained therapeutic aflibercept levels. These findings support the tolerability and efficacy of staggered dosing, indicating the potential for bilaterally relevant aflibercept levels with ixo-vec, due to immune response confinement to the dosed eye.

publication date

  • February 10, 2025

Identity

PubMed Central ID

  • PMC11910100

Scopus Document Identifier

  • 85218907601

Digital Object Identifier (DOI)

  • 10.1016/j.omtm.2025.101430

PubMed ID

  • 40092639

Additional Document Info

volume

  • 33

issue

  • 1