First surgery using Orbit subretinal delivery system to deliver AMD gene therapy performed
The first surgery using the Orbit subretinal delivery system to deliver GT005 to a patient with geographic atrophy secondary to dry age-related macular degeneration has been conducted in the ongoing phase 1/2 FOCUS trial.
Jeffrey Heier, MD, conducted the surgery using Gyroscope Therapeutics’ proprietary Orbit subretinal delivery system (Orbit SDS) to deliver GT005, an investigational gene therapy, without the need for a vitrectomy or retinotomy.
“The Orbit SDS is a very elegant way to deliver the gene therapy without actually having to go inside the eye, into the vitreous cavity and without having to make a subretinal entry site. … This approach minimizes the risks of intraocular surgery associated with a vitrectomy or creation of one or several retinotomies,” Heier told Healio/OSN.
The device creates a safe and standardized delivery of the gene therapy in the subretinal space, potentially improving on current delivery methods by limiting surgical variability, eliminating the need for a vitrectomy and negating the possibility of losing gene therapy through a retinotomy, Heier said.
The subretinal space is accessed by advancing a flexible cannula through the suprachoroidal space, and a microneedle inside the cannula is advanced to deliver the gene therapy beneath the retina, according to a company press release.
“Once we place the cannula into the suprachoroidal space, we then use a chandelier light pipe and a microscope to visualize the cannula as it extends posteriorly. We advance the cannula into the position that we want, which is usually outside the arcades, a certain distance from the atrophy and from the preferred retinal focus,” Heier said. “Once we are in the appropriate position and have adequate visualization, we extend a curved needle that goes through the choroid and into the subretinal space. To ensure that we are in the proper location, we infuse BSS to create a small fluid bleb. Once the bleb is visualized, we inject the gene therapy into the existing bleb.”
The ongoing phase 1/2 open-label clinical FOCUS trial is evaluating the safety and dose response of GT005 in geographic atrophy secondary to dry AMD. Three doses of GT005 are being studied in the trial, which now includes a dose-expansion cohort and two cohorts using the Orbit SDS to deliver GT005, according to the release.
The company has additionally announced the phase 2 multicenter, randomized, controlled HORIZON trial is underway, with the first person dosed with GT005 by Heier in the U.S. The intention of the 48-week trial is to evaluate safety and effectiveness of GT005 in approximately 180 patients with geographic atrophy secondary to dry AMD who have been stratified by AMD genotype subgroup, according to a separate press release.
The FDA has granted a second fast track designation to GT005 for treatment of geographic atrophy in people with variants in their complement genes, according to the release.
Editor’s note: On Nov. 11, 2020, this article was updated to include new information regarding the HORIZON trial and FDA action.