UPDATED: NIH says viral vector for delivering gene therapy to treat blindness shows promise, Wall Street less sure

Gene therapy delivered via a viral vector showed promise in delaying vision loss in patients with the inherited disorder Leber congenital amaurosis, albeit only temporarily.

The gene therapy works by giving the retina instructions on how to build the RPE65 protein, which is deficient in people with the condition due to a genetic mutation of the gene responsible for manufacture of the protein. A lack of the protein causes the retinal cells to die, leading to vision loss, explains the National Institutes of Health, which funded the research.

In this case, the re-engineered viral vector not only carried the genes to retina following injection, it also produces a healthy form of the RPE65 gene. It is administered via injection.

"Gene therapy for LCA demonstrated we could improve vision in previously untreatable and incurable retinal conditions," said Dr. Samuel G. Jacobson, leader of the clinical trial at the University of Pennsylvania's Scheie Eye Institute in Philadelphia. "Even though the current version of the therapy doesn't appear to be the permanent treatment we were hoping for, the gain in knowledge about the time course of efficacy is an opportunity to improve the therapy so that the restored vision can be sustained for longer durations in patients."

While the NIH touted the research, Wall Street wasn't thrilled because the beneficial effects on vision began to fade after one to three years, meaning commercializing costly gene therapy remains a challenge. Spark Therapeutics' shares plunged 16% on early trading on the news Monday, resulting in the dismemberment of about $200 million in value, before rebounding; the stock ended the day down 6.5%. 

The company's lead therapy delivers a functional copy of the RPE65 gene to Leber congenital amaurosis patients, but Spark insisted that the results of the study shouldn't be looked upon as harmful to the candidate's chances. "The clinical results that Spark has seen to date are significantly different from those reported in by Jacobson and his team. Spark's completed trials suggest that one-time administration of SPK-RPE65 produces long-lasting effects that have persisted for more than four years for the earliest-treated patients. Investigators reported that following a single injection of SPK-RPE65, children in Spark's previous trials no longer depended on visual aids to carry out classroom activities, and were able to walk and play more like normally sighted children," the company said in an email to FierceDrugDelivery.

The test will come in the second half the year, when Spark is scheduled to report results of the candidate's ongoing Phase III pivotal trial.

"We now have six years of data showing that a gene therapy approach is safe and that it successfully improves vision in people with this blinding disease," said Dr. Paul A. Sieving, director of NIH's National Eye Institute, about the NIH-funded study. "As with any application of a novel therapy, it now needs to be fine-tuned. More research is needed to understand the underlying biology and how we can preserve or restore photoreceptors for a lifetime. Restoring vision is at the heart of the NEI's Audacious Goals Initiative, an effort to strategically fund research aimed at developing the knowledge and technology to make this goal a reality."

The NEI's release of the study results occurred on the same day as it announced it is awarding up to $17.9 million over the next 5 years to find new therapies for blindness.

- read the release

Editor's Note: This article has been updated to include additional information from Spark.