Analysis of Aflibercept Expression in NHPs following Intravitreal Administration of ADVM-022, a Potential Gene Therapy for nAMD. Academic Article uri icon

Overview

abstract

  • Several standard-of-care therapies for the treatment of retinal disease, including aflibercept, inhibit vascular endothelial growth factor (VEGFA). The main shortcoming of these therapies is potential undertreatment due to a lack of compliance resulting from the need for repeated injections. Gene therapy may provide sustained levels of anti-VEGFA proteins in the retina following a single injection. In this nonhuman primate study, we explored whether ADVM-022, a recombinant adeno-associated virus (AAV) vector designed to express aflibercept, could induce anti-VEGFA protein levels comparable with those observed following a single-bolus intravitreal (IVT) injection of the standard-of-care aflibercept recombinant protein. The results demonstrated that intraocular levels of aflibercept measured at 56 days after a single IVT injection of ADVM-022 were equivalent to those in the aflibercept recombinant protein-injected animals measured 21-32 days post-administration. ADVM-022-injected animals exhibited signs of an initial self-limiting inflammatory response, but overall all doses were well tolerated. ADVM-022 administration did not result in systemic exposure to aflibercept at any dose evaluated. These results demonstrated that a single IVT injection of ADVM-022 resulted in safe and efficacious aflibercept levels in the therapeutic range, suggesting the potential of a gene therapy approach for long-term treatment of retinal disease with anti-VEGF therapy.

authors

  • Kiss, Szilard
  • Grishanin, Ruslan
  • Nguyen, Aivan
  • Rosario, Romeo
  • Greengard, Judith S
  • Nieves, Julio
  • Gelfman, Claire M
  • Gasmi, Mehdi

publication date

  • June 12, 2020

Identity

PubMed Central ID

  • PMC7341454

Scopus Document Identifier

  • 85087476737

Digital Object Identifier (DOI)

  • 10.1016/j.omtm.2020.06.007

PubMed ID

  • 32671137

Additional Document Info

volume

  • 18