Rare Disease Report

Foundation Fighting Blindness CRO Talks Luxturna

OCTOBER 13, 2017
Mathew Shanley
Stephen Rose, PhDYesterday, the U.S. Food and Drug Administration’s (FDA) Cellular, Tissue and Gene Therapies Advisory Committee met to review the data presented by Spark Therapeutics as the company continues its attempts to obtain approval of Luxturna (voretigene neparvovec) to treat vision loss caused by a mutation in the RPE65 gene.

Stephen M. Rose, Ph.D., Chief Research Officer for the Foundation Fighting Blindness presented at the FDA’s Advisory Committee meeting on Thursday. Rare Disease Report sat down with him on Wednesday afternoon to discuss Luxturna, its mechanism of action, and why the FDA’s review of it is so vital to patient’s suffering from retinal diseases.

RDR: What exactly happens to somebody who has a mutation in the RPE65 gene?

Rose: Think of your eye as a camera; the front of your eye is the lens and the back of your eye – or the retina – is the film of the camera or the digital chip. The bottom line is that, in LCA, that’s what stops working. What happens is that the back of the eye degenerates, like the film of a camera becoming fogged, and it’s no longer useful as if it were exposed to the light. In these particular cases, it’s because the gene, RPE65, is not doing what it’s supposed to do. This retinal degeneration should be viewed as if it were a hybrid car; you take your foot off of the brake, and the engine shuts off. What I mean by that is that your retina is not getting the “gas” that it needs, and therefore, it’s not working, but it hasn’t necessarily died. It’s not like you turned the key to turn the engine off permanently.

So, by this gene therapy, what we’re doing is we’re putting back in a protein that is responsible for generating the “gas” that the retina needs to work. In several cases of LCA with any of the 22 gene mutations responsible for it, the retina is actually dead at birth; that’s not the case here. This is a case where, if you can resupply the “gas” that’s needed in the retina, the portion of it that hasn’t died will start to work again.

RDR: What can people expect from the FDA Committee on Thursday?

Rose: At the FDA Committee, they’re going to be showing that, if (Luxturna) is given, and depending on who gets it with respect to their specific mutation in the RPE65 gene, what will be seen in regard to the different amount of restoration of functional vision? How are they measuring that? Normally, if I’m dealing with macular degeneration, which is not a rare or orphan disease, you lose your central vision. Central vision is responsible for color, being able to read, and day vision. In age-related macular degeneration (AMD), you have a big black spot in the middle of your vision; you can’t read, you can’t drive a car, you can’t even knit or sew.

Leber congenital amaurosis (LCA) is different. In LCA, you lose your vision from the outside in, rather from the inside-out. As a kid, if you’ve ever looked through a toilet paper roll and used it as a telescope – Bingo! That is what happens in LCA. Your vision constricts to the point that it’s like you are looking through a toilet paper roll. Now, that vision can be 20/20, but you just have this restricted, almost pinhole-like vision. By losing your peripheral, what you’re losing is your night vision, your ability to see in low light, and your black and white vision.

RDR: How has Luxturna been tested?

Rose: The testing for this gene therapy recognizes that, in reality, a number of these individuals retain the ability to read. So, what are they testing? They’re testing the ability of people to be mobile in low-light situations. Can people with these diseases now go out during dusk? Can they see around the house, so that they’re not tripping over things? That’s what the mobility test is looking at. In fact, what this showed was that the drug brought back vision in these individuals in their ability to be mobile, and that is huge. This means that these individuals are mobile again and don’t need, necessarily, a cane.

Not everybody got the same response. There are different mutations in the gene that come on in different ages and different severities. Bottom line, though, is that it had a positive effect in allowing people to be self-sufficient and provided a better quality of life. Low and behold, it didn’t meet a secondary endpoint of meeting visual acuity, however clinicians recognize the impact and effect it can have on patients’ lives.


The FDA’s Cellular, Tissue and Gene Therapies Advisory Committee voted 16-0 in favor of Luxturna yesterday, and the PDUFA action date is set for January.

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