Gene transfer agent in development

Fort Lauderdale, FL-Phase I testing is under way to evaluate intravitreal anti-vascular endothelial growth factor (VEGF) gene delivery as a treatment for exudative age-related macular degeneration (AMD), said Abraham Scaria, PhD, at the annual meeting of the Association for Research in Vision and Ophthalmology.

The anti-VEGF molecule is a hybrid protein that links the second immunoglobulin (IgG)-like domain of VEGF receptor Flt-1 to a human IgG1-Fc. It was selected as the lead candidate based on results from in vitro screening, which showed it to be a potent inhibitor of VEGF.

Dr. Scaria presented favorable findings from a 12-month, formal GLP toxicity study of intravitreal injection of AAV2-sFLT01 in cynomolgus monkeys that also demonstrated long-term efficacy in preventing laser-induced CNV and persistent gene expression.

"Current treatment of neovascular AMD using anti-VEGF agents can be very effective, but generally requires monthly intravitreal injections," said Dr. Scaria, senior scientific director, Genzyme Corp., Framingham, MA. "The results from extensive preclinical testing of AAV2-sFLT01 are encouraging in suggesting this gene therapy approach may be a viable alternative for achieving a prolonged anti-VEGF effect and obviating the need for repeated injections."