FDA Advisory Committee Recommended Approval of First Gene Therapy For Inherited Eye Disease

MedicalResearch.com Interview with:
Dr. Stephen M. Rose, PhD Chief Research Officer Foundation Fighting BlindnessDr. Stephen M. Rose, PhD
Chief Research Officer
Foundation Fighting Blindness

Dr. Rose discusses the FDA advisory panel unanimously recommended approval of Spark Therapeutics’ Gene Therapy Luxturna  for the treatment of patients with vision loss due to confirmed biallelic RPE65-mediated inherited retinal dystrophies, a group of rare blinding conditions caused by one of more than 220 different genes.

MedicalResearch.com: Would you tell us a little about IRD? Whom does it affect and how?  How common is this disorder?

Response: The retina at the back of the eye is responsible for collecting light and turning it into signals that are transmitted to the brain and interpreted as vision. Think of the retina as the film in a camera, or more recently the sensor at the back of a digital camera. Inherited rare retinal degenerations are when the retina at the back of the eye deteriorates and loses its ability to capture light, thereby leading to blindness.

iRDs can affect anyone, no matter race or ethnicity. These are inherited conditions that are passed down from parents to children, if a parent or both parents are either affected already or are carriers for a variant in any of the over 250 genes responsible for retinal degeneration.

There are over 15 different types of iRDs, with retinitis pigmentosa being the most common with a US affected population around 100,000. The rest of the iRDs make up another approximately 100,000 affected individuals in the US, so there are about 200,000 total affected individuals in the US. Worldwide these iRDs affect somewhere around one to two million individuals.

MedicalResearch.com: How does voretigene neparvovec reverse the potential for blindness in these individuals?  What is the vector for transmission of the gene?  Is replacement of the affected gene permanent?  Is further immunosuppression required? 

Response: Voretigene neparvovec, called Luxterna™ by Spark Therapeutics, introduces a good copy of the RPE65 gene into the retina of an individual who has an iRD (either Leber’s Congenital Amaurosis 2 or retinitis pigmentosa 20) due to inheriting non-functional copies of the RPE65 gene from both parents. Introduction of a functional copy of the gene stops further retinal degeneration and also reactivates retinal cells that are not working but not dead.

The functional copy of the RPE65 gene is introduced to the retina using a non-disease causing virus as the gene carrier- in this case adeno-associated virus (AAV). Basically the virus’ DNA is replaced with the RPE65 gene and the AAV-RPE65 vector (which is what the combination of the virus shell and the replacement DNA, in this case, the RPE65 gene) is injected into the retina so the gene gets to the retinal cells that need it.

So far there are individuals who have received the gene therapy and are still seeing its effects 10 years after the injection but no one knows for sure if it really an once-in-a-lifetime effect until people get to the end of their life after treatment.

Further immunosuppression besides the initial steroids to reduce inflammation from the injection itself appears to be required, based on results seen to date.

MedicalResearch.com: What should readers take away from your report?

Response: The take away from this is that not only this gene therapy is a viable long term treatment that can restore functional vision to individuals with RPE65 caused LCA and RP, but that this demonstrates the potential for gene therapy being a viable and successful treatment for many other iRDs. The introduction of the functional RPE65 gene into individuals who have severe vision loss to complete blindness restores functional vision to these individuals and paves the way for many other such gene therapies. In fact, there are currently over 12 gene therapy clinical trials ongoing for iRDs across the world at the moment with many more close to beginning clinical trials, and FFB has funded early and translational research for all of these at one point.

MedicalResearch.com: What further diseases/research are you planning to investigate?

Response: The Foundation Fighting Blindness funds research that would provide potential treatments for all the iRDs, not matter what gene is causative. These are so-called “pan” treatments and run the gamete from oral medications to other gene therapies and stem cell therapies. As I pointed out earlier, there are over 15 different iRDs and over 250 genes responsible for iRDs and the Foundation is committed to meeting our mission that was established when the Foundation Fighting Blindness was established in 1971- that is that no person would ever hear “you have an iRD, go home, learn Braille, get a guide dog or a cane, there is nothing we can do for you.” Instead they would hear “Ok, you have an iRD, but don’t worry, you will not lose your vision, and there is a treatment for that.”

The Foundation funds research worldwide to achieve this goal and to derisk research to the point that biotech and pharma will acquire these projects and take them through the regulatory path to commercialization. This is what happened with RPE65- FFB started funding the research that identified the RPE65 gene as being responsible for LCA2 and RP20, through the animal studies that provided proof of concept and the early clinical trials conducted at CHOP. After those promising results, Spark Therapeutics was established and Spark took on the project and brought it through the phase III clinical trial and filed for approval with the FDA. This is the model that FFB sees as most effective to get treatments to individuals affected by iRDs. 

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LUXTURNA™ (voretigene neparvovec) for the treatment of biallelic RPE65-mediated inherited retinal disease:

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Last Updated on November 8, 2017 by Marie Benz MD FAAD