Jeffrey Heier, MD on RGX-314 Gene Therapy

Jeffrey Heier, MD, co-president and medical director of the Ophthalmic Consultants of Boston, presented at the 2017 American Society of Retina Specialists Annual Meeting on RGX-314, a gene therapy treatment for designed to alleviate the overall treatment burden for patients with wet age-related macular degeneration (AMD) through a single subretinal injection.

Currently, a phase 1, open-label study is in the enrolling process for 18 patients who had been previously treated for wet AMD and were responsive to previous anti-VEGF therapy. The study will administer RGX-314 at 3 exploratory doses, with primary outcome measures focused on safety and tolerability at 24 weeks.

Jeffrey Heier, MD: What we presented today was an overview of the pretrial, collaborative effort of REGENXBIO and the investigating investigators - the surgeons. There was a great deal of work that's gone into this. There have been several gene therapy trials both from an intravitreal and subretinal delivery in the past. Those studies have had limited success, and there's a variety of reasons why that's so, but probably the most important reason is an inadequate expression.

So RGX-314 is the gene therapy construct that we're delivering subretinally. This has demonstrated much higher expression in preclinical models. The reason the decision was made to go subretinal versus intravitreally, despite the fact that they have much higher expression is several-fold. One the feeling is that you get much higher expression subretinally is that you're delivering it right to the RPE cells that will transduce it. The the second issue is concerning neutralizing antibodies, and there have been studies that have shown the presence of neutralizing antibodies, which are quite common because of a fair amount of exposure to AAVs. These neutralizing antibodies can lead to decreased or no expression these subretinal space is believed to be an immunologically privileged space, and so delivering them subretinally may minimize or alleviate the impact of neutralizing antibodies.