Eye Treatment Closes In on Being First Gene Therapy Approved in U.S.

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What could become the first gene therapy to win approval in the United States moved closer to market on Monday, when its developer announced that the medicine had succeeded in a late­stage clinical trial in treating an inherited eye disease that can cause blindness.

The developer, Spark Therapeutics, said the treatment had allowed people with certain so­called inherited retinal dystrophies to more easily maneuver in dimmer light than they could before. The company said it planned to apply to the Food and Drug Administration next year for approval to sell the product.

“We saw substantial restoration of vision in patients who were progressing toward complete blindness,” Dr. Albert M. Maguire, a professor of ophthalmology at the University of Pennsylvania and a lead researcher in the study, said in a news release being issued by Spark.

Dr. Katherine High, Spark’s president and chief scientific officer, said this was the first successful randomized, controlled trial for any gene therapy aimed at an inherited disease.

“I’ve been working in gene therapy for most of my career,” she said. “It’s been a long time coming, and I’m delighted.”

Besides encouraging the once beleaguered field of gene therapy, the results — if interpreted positively by investors — could help lift biotechnology stocks, which have been battered recently by concerns over a backlash against high drug prices.

Still, much remains unknown. Spark did not provide the actual trial data, saying only that the treatment achieved the main goal of the study as well as two out of three of its secondary goals. It is also unclear what the F.D.A. will deem sufficient for approval of the product. Spark’s stock had slumped in the last two months as it changed how it would measure the results of the trial.

Gene therapy involves putting healthy genes into the body to take the place of mutated genes that cause disease. There have been hundreds of trials of gene therapy in humans since 1990, and none have resulted in a medicine winning approval from the F.D.A. One gene therapy for an extremely rare disease was approved in Europe in 2012, but there are questions about its effectiveness.

In the last few years, prospects and results have improved and several new gene therapy companies have gone public, including Spark. Even so, two gene therapy companies, Celladon and Avalanche Biotechnologies, had disappointing trial results recently.

Spark’s product, called SPK­RPE65, is aimed at retinal diseases caused by mutations in a gene called RPE65; this gene plays a role in maintaining the health of the photoreceptors in the eye. Spark estimates there are 3,500 people in the United States and five major European countries with these conditions, though the treatment would not be expected to help people whose disease had progressed past a certain point.

The 31 patients in the study, ranging in age from 4 to 44, have one type of Leber’s congenital amaurosis, which causes night blindness and an erosion of peripheral vision, and can eventually lead to total blindness.

Twenty­-one of the participants were randomly assigned to have a virus carrying the RPE65 gene implanted into their eye via a surgical procedure. The 10 others, the control group, received no treatment.

The main measure of effectiveness was how much light participants needed to successfully navigate an obstacle course of sorts — following black arrows on a white tile floor, going up and down steps, and avoiding objects like wastebaskets. There were seven possible levels of illumination ranging from that of a moonless summer night to that of a brightly lit office.

One year later, those who had received the treatment improved by an average of two light levels, meaning they could complete the course in dimmer light than before, Dr. High said. That was better than those in the control group by a statistically significant amount, though she declined to provide the results for the control group. Two-­thirds of those in the treated group were able to complete the course in the dimmest light, the level corresponding to a moonless summer night.

The company said there were no serious side effects or immune system reactions in the trial.

“It’s very exciting,” said Gordon Gund, chairman of the Foundation Fighting Blindness, which helped pay for the development of the therapy and some earlier studies of the therapy. He said that while the condition Spark is treating is rare, “this really provides us a platform for many other successful gene therapies.”

One question is how long the effect will last. Theoretically, gene therapy could provide a permanent fix. (Spark claimed the ticker symbol “ONCE” when it went public early this year.)

But some academic groups that tried a similar RPE65 gene therapy reported earlier this year that the effect wore off after one or more years.

Jeffrey D. Marrazzo, chief executive of Spark, said the effects from earlier, small trials of his company’s therapy had, so far, generally lasted for several years. Some of those earlier results were substantial: One boy, who had relied on canes and an aide in the classroom, became able to play baseball and read the blackboard.

In the new trial, the treatment did not achieve one of the secondary goals — improving visual acuity, as measured by reading letters on an eye chart, by a statistically significant amount.

Dr. Julia A. Haller, ophthalmologist in chief at the Wills Eye Hospital in Philadelphia and president of the Retina Society, said that visual acuity was “not an endpoint that would be expected to improve dramatically,” because the therapy was aimed at night vision and peripheral vision.

Dr. Haller, who was an unpaid consultant in the trial, said the presentation of data from the trial would be the “hottest thing” on the program at the Retina Society’s annual meeting in Paris this weekend. “To get to this point, for this to come to fruition, is huge,” she said.

The therapy was originally developed by Dr. High and her colleagues at the Children’s Hospital of Philadelphia. She co­founded Spark in 2013. In a somewhat unusual move, the hospital invested more than $30 million to help the company get started. The hospital now owns more than a third of the company, a stake worth close to $400 million.

 

 

A version of this article appears in print on October 5, 2015, on page B3 of the New York edition with the headline: Eye Treatment Closes In on Being First Gene Therapy Approved in U.S. .


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