Yesterday, a landmark publication in The Lancet, a prestigious journal, showed that gene therapy can improve vision in people living with a rare blinding eye disease. The study examined the effects of an experimental gene therapy – voretigene neparvovec – to treat an inherited blinding eye disease caused by mutations in the RPE65 gene. RPE65 mutations are one of the genetic mutations that underlie the disease Leber congenital amaurosis (LCA), which causes severe loss of vision at birth or in childhood.
At a recent ophthalmology conference, I was very fortunate to view some of the video data that showed trial participants navigating a maze test before and after receiving this experimental treatment. The results were striking. Before the treatment, patients’ vision was so poor, they could not walk through the maze without wandering off the course. After the treatment, patients could step over obstacles in the maze as they followed a path of arrows, responding accurately to cues to turn left or right.
The phase 3 trial tested both functional vision (i.e., the ability to navigate through a maze in different levels of light) and visual function. Visual acuity is a common indicator of visual function, which is measured by ability to read a standardized eye chart. The paper provides an analysis of these tests and concludes that the functional vision results are statistically significant; this means that there is excellent “gold standard” evidence that the gene therapy (voretigene neparvovec) improves functional vision in patients living with an inherited blinding eye disease caused by biallelic RPE65 mutations (biallelic means that there are mutations in both copies of the RPE65 gene).
We recently shared our excitement when Spark Therapeutics, who is leading the development of voretigene neparvovec, made a submission to the Food and Drug Administration (FDA), a critical step toward making this an approved treatment.
This study is incredibly important for the future of gene therapy. It marks the very first phase 3 randomized controlled trial of a gene therapy for a genetic disease! This matters because clinical trials are an essential kind of research that test if experimental treatments are safe and effective. A phase 3 clinical trial can only be initiated after earlier phases have resulted in promising outcomes.
First and foremost, a “first-in-human” clinical trial, or a phase 1 trial, is only possible after significant laboratory research has demonstrated that a new treatment is safe and effective in animal models of the disease. These early trials are designed to test if the intervention (the experimental treatment) is safe in people. If these safety trials work out, phase 2 trials are designed to test if the intervention is effective. Phase 3 trials are the gold standard to test if an experimental treatment works – these trials involve larger numbers of people and randomization, which means that some of the participants are randomly assigned to receive the intervention while others receive a placebo (which is basically a fake intervention, such as a sugar pill). Careful study design makes it possible to evaluate if the treatment is working. The excellent news is that the results from this study show that this gene therapy works.
Encouraged by these successful results, Spark Therapeutics, who is leading the development of voretigene neparvovec, made a submission to the Food and Drug Administration (FDA), a critical step toward making this an approved treatment.
Will this treatment work for you? It will only work for people who are living with an inherited blinding eye disease caused by bilallelic RPE65 mutations. These mutations are one of the genetic causes of Leber congenital amaurosis (LCA). The only way to find out if a gene therapy might work for you is to get your genetic testing done. When it’s ready, we want this treatment to come to Canada!! Help us get ready by taking these three steps: 1) get your genetic testing done; 2) reach out to us here at the FFB; and 3) enrol in the FFB Patient Registry!! We need your help to raise awareness about the need for these innovative treatments in Canada.
Read about the Study:
Russel et. al. 2017. Efficacy and safety of voretigene neparvovec (AAV2-jRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. The Lancet.