Bleb placement change for subretinal gene therapy may prevent guttering
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WAILEA, Hawaii — Retinal pigmentary changes were seen in 67% of patients in the phase 1/2 safety study of RGX-314, a gene therapy delivered subretinally for the treatment of AMD.
One case was considered severe, and location of the bleb placement may be related.
“Pigmentary change is something that’s definitely been noted in a dose-dependent fashion, suggesting that it’s not just the bleb mechanical effect,” Allen C. Ho, MD, said at Retina 2021.
Even so, bleb location could be a factor in the one severe case. Initially, blebs were placed superiorly, and in the one patient with pigmentary changes and vision loss, the pigmentary changes guttered through the central macula, which is presumed to be associated, Ho said.
“That’s the presumption,” Ho said. “It’s the conservative presumption.”
In the future, Ho said the blebs will no longer be placed superiorly.
“Moving forward, all the blebs are not going to be able to be guttered from above the arcades through the central macula. All the blebs will be administered inferiorly. I anticipate as we move forward in the phase 3 pivotal trial now that we’ll be seeing pigmentary changes, but they won’t be affecting central vision because you can’t gutter upward,” he said.
In eyes that demonstrate pigmentary changes that do not fall within that bleb space, it is possible that there may be some slight migration of the subretinal gene therapy, Christina Y. Weng, MD, MBA, said.
“More of a concern is whether there is a subclinical inflammation that’s causing this,” she said.
Regarding the safety trial, Ho said the gene therapy delivery has been “incredibly safe.”
Considering the high dose of viral vector particles, “I was surprised by that,” Ho said. “But the data are really compelling that these are stone cold quiet eyes in this subretinal injection program.”
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Kaiser P, et al. New treatments for retinal vascular disease. Presented at: Retina 2021; May 9-14, 2021; Wailea, Hawaii.
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