Avni P. Finn MD, MBA
Vanderbilt Eye Institute, Nashville, TN
One of the highlights of Friday’s Retina Society Meeting was the presentation of the first-time results of the AAVIATE Phase II trial presented by Dr. Nikolas London.
The trial evaluated the efficacy, safety, and tolerability of suprachoroidal delivery of RGX-314. RGX-314 is a gene therapy intervention using an adeno-associated virus, AAV8, to deliver a transgene for a soluble anti-VEGF fab, aimed at producing continuous anti-VEGF therapy in the eye. This has been delivered via a subretinal route in patients with previously treated neovascular AMD (nAMD) in an ongoing Phase I/IIa trial with good safety and tolerability now two years out.
In this trial, RGX-314 was delivered into the suprachoroidal space using the Clearside microinjector via an in-office procedure. The primary endpoint was vision at month 9 in patients treated with RGX-314 compared to patients who received monthly ranibizumab. Fifty patients were enrolled to date and the dose was escalated between the three enrolled cohorts beginning with a dose of 2.5 x 1011 gene copies/eye in the first cohort. On average the patients enrolled in the three cohorts had about a two-year history of nAMD with injections on average every 5-6 weeks.
Vision was stable at month 6 in the RGX-314 group with a small difference in visual acuity compared to the monthly ranibizumab group. Monthly ranibizumab patients gained about 3 letters more at 6 months. Central retinal thickness also was stable at month 6 with a 25-micron difference between the monthly ranibizumab group and the RGX-314 group. Overall, the treatment was well-tolerated and to date the trial has shown no serious side effects. There were 4 cases of mild intraocular inflammation, which was treated with a short course of topical steroids. Most exciting was that there was a 75.9% reduction in treatment burden in the suprachoroidal treatment group.
The study has now been expanded to another cohort with a higher treatment dose. These results are promising given the ability to essentially produce an anti-VEGF factory in eyes requiring a high burden of intravitreal injections via an in-office procedure. In addition to avoiding surgery, suprachoroidal delivery may also provide an alternate route for compartmentalized, targeted delivery of the therapy. However, important considerations were raised by the audience regarding the effects of chronic anti-VEGF suppression on the retina, particularly as it relates to atrophy.