Patients undergoing treatment for wet age-related macular degeneration (AMD) have a tremendous treatment burden depending on their response to medical therapy. However, a new therapy administered once subretinally might alleviate that burden.
RGX-314 gene therapy (REGENXBIO), an adeno-associated virus serotype 8 (AAV8) vector that delivers an anti-vascular endothelial growth factor (anti-VEGF) Fab protein, is under study to treat neovascular AMD by delivering the gene therapy construct. However, designing a surgical therapy is not for the faint of heart.
Jeffrey Heier, MD, co-president and medical director, Ophthalmic Consultants of Boston, discussed the challenges facing the investigators and the early surgical outcomes.
Gene therapy trials of intravitreal and subretinal delivery of therapeutic agents have been undertaken previously, and one of the most important reasons for the limited success of these enterprises is inadequate expression, Dr. Heier said.
The goal of the RGX-314 gene therapy platform is higher protein expression over a longer period with a lower risk of immune response.
“Most of the studies performed to date have used the adeno-associated virus 2 (AAV2) vector,” Dr. Heier said. “However, the AAV8 vector has demonstrated more efficient protein expression in the retinal pigment epithelial cells. RGX-314 has been reported to be on the order of 10-fold higher than results that were previously reported with the AAV2 vector.”