RPE65 gene therapy update

This summer, Fighting Blindness welcomed the publication of pivotal phase 3 clinical trial data for an investigational, potential one-time gene therapy to treat an inherited rare form of blindness 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.

The gene therapy known as Voretigene Neparvovec (LUXTURNA™), developed by Spark Therapeutics, replaces the defective gene by using harmless viruses to deliver a working copy of the RPE65 gene directly to the patient’s eye.

Results shared in The Lancet, a prestigious scientific journal, showed that following treatment, study participants demonstrated improved functional vision, light sensitivity and visual field function.

It is extremely important, especially for those living with sight loss, that clinical trials measure things that are relevant to the individual and their daily experiences. Last year at Retina 2016, Fighting Blindness were delighted to have Dr Daniel Chung from Spark Therapeutics present at the Public Engagement Day.

Dr Chung shared with the audience some of the video data that showed trial participants navigating a maze test before and after receiving this experimental treatment. This maze was designed to measure an individual’s functional vision, the vision we use day to day for different tasks.

One of the first things that cause a problem for people with RPE65 diseases is difficulty seeing in dim light, so the participants in the phase 3 trial were asked to complete the maze at different light levels. Following treatment, participants significantly improved their ability to navigate the maze course under very low light conditions, indicating an improvement in vision.

Earlier this year, Spark Therapeutics made a submission to the Food and Drug Administration (FDA) to have the gene therapy approved so that it can go on the market in the US. This followed in July with a submission to the European Medicines Agency (EMA) to gain market approval here.

With over ten years in the making, this study marks the very first phase 3 randomized controlled trial of a gene therapy for a genetic disease. Its advancement is incredibly important for the future of gene therapy and has paved the journey for future therapies coming down the line. It also highlights the importance of the Target 5000 programme.

Receiving a confirmed genetic diagnosis and being part of our national register will place Irish patients at the forefront of this new era of clinical trials and therapies for rare inherited diseases of the retina.