Dr. Kiss said researchers have not yet had success with a gene therapy trial for AMD, but that may have been a result of the molecules chosen or the vectors used to deliver the therapy.
“It’s possible the AAV2 vector is not the most optimal vector to be used for gene therapy,” Dr. Kiss said.
Dr. Kiss detailed some of these issues by talking about a recently published study that used AAV2-soluble FLT.1 The study by Heier et al represented the first clinical trial to test intravitreous injection of AAV2-sFLT01 for the treatment of AMD.
The trial’s primary goal was to assess safety. A secondary goal was to assess anti-permeability activity, which required withholding anti-VEGF injections, but only if visual potential was not compromised.
“In this phase I, dose-escalating trial, subjects were treated but subjects that had antibodies did not have any protein expression,” Dr. Kiss said. “In those subjects where there were no antibodies, some protein expression was seen. Clinical efficacy was variable.”
RegenXBio is using a proprietary technology in vector AAV8-NAV that delivers (essentially) something akin to ranibizumab, Dr. Kiss said.
“When you deliver AAV8 to the subretinal space, there is more transfection than if you deliver AAV2,” Dr. Kiss said. “There is more of the molecule in the vitreous–up to 1,000-fold to 2,000-fold higher with an AAV8 vector than can be achieved with a subretinal delivery with an AAV2 vector.”
(Editor’s note: RegenXBio has completed dosing in its third cohort of 6 patients. Topline data readout is expected in late 2018.)