Spark’s gene therapy shows great promise in restoring sight

Data from a phase 3 trial of a potentially groundbreaking gene therapy suggests it can restore vision in patients with a rare inherited eye condition.

Spark Therapeutics is developing voretigene neparvovec (SPK-RPE65)  to treat inherited retinal disease (IRD) caused by mutations in the RPE65 gene, and yesterday announced some impressive results in a trial of 29 patients.

The field of gene therapy and regenerative medicine has been developing over the last 10 years, with a number of companies now taking their technologies into pivotal clinical trials. Spark, a spin-out of the Children’s Hospital in Philadelphia, is emerging as one of the best bets for success, thanks to some encouraging data.

The pivotal portion of the trial released yesterday is the first successful randomised, controlled phase 3 trial ever completed for a gene therapy for a genetic disease.

The disease in question is RPE65-mediated inherited retinal dystrophies, or IRDs. These are a family of rare, blinding conditions caused by mutations in the genes of the retina. RPE65 is an enzyme that helps turn light into electrical signals that the brain recognises as vision, but when this is missing or faulty, vision problems arise.

The latest data includes positive outcomes for nine crossover patients who received SPK-RPE65 a year ago, along with promising longer term results from an original group of 20 patients.

Results from the group of nine patients one year on from treatment found that eight of them showed improvement in their vision.

The company uses a test to assess how well they can find their way across a room in different levels of light, and all eight responders succeeding in navigating the course at 1 lux, the lowest level of illumination, equivalent to a moonless summer night.

This adds to similarly encouraging data from the other patients observed over at least three years.

However analysts were also told that the drug’s regulatory filing will be delayed by six months to October 2017 because of chemistry, manufacturing and controls (CMC) issues.

Spark’s therapy is particularly striking as it requires just one administration, with no need for subsequent treatments. The drug has received breakthrough therapy designation from the FDA, as well as orphan product designation on both sides of the Atlantic.

The company is applying its gene therapy platform to a range of clinical and preclinical studies in genetic diseases, including inherited retinal diseases, liver-associated diseases, such as haemophilia, and neurodegenerative diseases.

Spark has two lead assets in haemophilia: SPK-9001 is being developed with Pfizer in a phase 1/2 trial for haemophilia B; and SPK-8011, a preclinical candidate for haemophilia A.

SPK-9001 has also received breakthrough therapy designation, and part of a new wave of products for haemophilia which could reach the market by 2020.