Stephen R. Russell, MD: The Significance of New Voretigene Neparvovec-ryzl Data for IRD

Unique trial three-year follow-up data for voretigene neparvovec-ryzl treating inherited retina disease (IRD), as presented at the American Society of Retina Specialists (ASRS) Annual Meeting in Vancouver, BC, showed the gene therapy is capable of improving patients' visual function over a long period of time.

What's interesting is that the data is similar to that presented to the US Food and Drug Administration (FDA) for the therapy's approval last year, Stephen R. Russell, MD, told MD Magazine®. Russell, a professor of vitroretinal diseases and surgery services director at University of Iowa Hospital & Clinics, reported the RPE65-targeting therapy improved both routine functional vision and vision capability versus control in patients with IRD.

Russell explained the brief history of gene therapy for retina disease, and how it led to him presenting the new data ASRS 2018 in the first place.

Stephen R. Russell, MD: There are many reasons why this is of potential interest. The first is that it's the first approved—it was approved in December of 2017. It was the first approved gene therapy treatment for an inherited disease of any kind, not just ocular disease, but any inherited disease.

There were 2 other gene therapy products which were approved, but both of them were for cells that were removed from the body, transformed, transfected with genes, and then placed back into the body. This gene therapy is true gene therapy, in vivo. So we're talking about placing the viral genomes under the retina, where they have access to the target tissue—which in this case is the retinal pigmented epithelium—and we're looking at how the disease responds to replacement of a missing functional copy of the gene.

In this case, the gene we're talking about is RPE65, which is the retinal trans isomerase, which is the enzyme that recycles vitamin A in the visual pathway and allows people to be able to see. So it's the visual pigment used for detection.

So this is the three-year follow-up, and normally I am not a big fan of presenting follow-up data—or five-year data—because frankly things don't generally happen that haven't already happened at the one-year or the primary endpoint of a trial. And that's true in this study.

So I'll ruin any suspense and just tell you in advance that the results are going to look very similar to the one-year primary endpoint data that we presented to the FDA. But the reason why I elected to come and give this talk is that there was before we started our trial there were 3 other trials looking at gene therapy for this particular gene, RPE65. One of those groups published a paper which claimed that by year 3, the durability of the treatment had completely worn off.

And so there were there have been ongoing concerns from payers, ongoing for concerns by treating physicians, inherited retinal disease specialists, about whether this kind of therapy—a gene intervention trial where you replace the gene—whether the genes can remain active. Because this is essentially a potentially one-and-done kind of treatment, it's potentially once-per-eye kind of treatment, and the question is whether it is going to last.

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