FDA advisors back gene therapy for rare inherited blindness

The US Food Drug and Administration (FDA) advisory committee has backed the use of gene therapy to treat a hereditary disease for the first time.

Luxturna has been tested to treat patients who have inherited retinal dystrophy, a disease caused when both copies of the RPE65 gene carry a mutation. The eyes' ability to respond to light is increasingly impaired and patients eventually become blind.

'This would be the first approved treatment of any sort for this condition and the first approved gene therapy treatment for the eye, in general,' Dr Paul Yang of Oregon Health and Science University told National Public Radio. 'So, on multiple fronts, it's a first and ushers in a new era of gene therapy', he added.

In a clinical trial of 31 people, sponsored by Spark Therapeutics and led by Professor Albert Maguire of the University of Pennsylvania, Luxturna significantly improved the visual outcome in people aged between four to 44 years old who received the drug as a one-time sub-retinal injection, compared to a control group.

The injection consisted of a genetically engineered adeno-associated viral vector, which contained the normal copy of the RPE65 gene. When injected into the retinal cells, the gene expressed the RPE65 protein: a vital enzyme for normal retinal function.

The effectiveness of the therapy was determined by using a novel approach: multi-luminance mobility testing, which assesses how well a person is able to navigate and move under different light levels. At one year post-treatment, those who had received treatment showed improved visual acuity, compared to the control group.

However, there were a few complications, including events related to the procedure and permanent retinal damage caused by use of prednisone medication. Taking into consideration, all 16 members of The Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) decided the efficacy data outweighed the safety risks, and gave favourable recommendation to the FDA to approve Luxturna.

In most cases, the FDA follows the recommendations set by advisory committee but there is currently a series of unanswered questions, as outlined in the FDA briefing document. These include: 'what additional data, if any, would be necessary to support such repeat administration?' and, 'at what stage of clinical presentation do the benefits of therapy outweigh the risks?'

Furthermore, the long-term effects of the treatment are unknown. Speaking to Nature, Professor Mark Kay, a geneticist at Stanford University, California, said: 'I think we still need to have major improvements in the technology before we're going to be able to cure these diseases, but along the way there may be treatments that help make improvements'.

A decision from the FDA on Luxturna is expected by early next year.