Success of Gene Therapy to Treat Blind Fades With Follow-Up

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A gene therapy that helped restore sight in patients with a rare form of childhood blindness appears to wane with time, a sign the cutting-edge field may not be able to cure some ailments with a single course of treatment.

Shares of Spark Therapeutics Inc., which is developing a similar treatment, fell 6 percent to $55.01 at the close in New York. The waning benefit was described in two studies this week in the New England Journal of Medicine. The studies didn’t use the same technique or active therapy as the trials under way from Philadelphia-based Spark.

Still, the results sound a note of caution for one of biotechnology’s hottest areas, where companies like Spark are developing treatments to repair genetic defects that cause disease. The researchers and companies crafting gene therapies need to work together to ensure the best methods are used, especially given the small number of patients who may benefit, investigators said.

In tests run in the U.S. and U.K., a corrected copy of the gene that makes a protein crucial for vision is injected into one eye. An in-depth examination of three early University of Pennsylvania patients found their eyesight improved in the treated eye for as much as three years. After that, the benefit started to trail off and the patients lost critical photoreceptor cells in the retina at the same pace as in their untreated eyes.

A second study from the University College London’s Institute of Ophthalmology and Moorfields Eye Hospital tracked a dozen patients who got varying doses of the gene therapy. Half reaped a modest benefit, with a small and temporary improvement in retinal sensitivity that peaked a year after treatment. Inflammation developed in the eyes of three patients, and two actually lost visual acuity.


While researchers are disappointed they don’t have a one-time treatment, the results are an “opportunity to improve the therapy so that the restored vision can be sustained for longer durations in patients,” said Samuel Jacobson, the lead researcher of the trial and a professor at Penn’s Scheie Eye Institute in Philadelphia.

The university researchers didn’t use the same treatment as Philadelphia-based Spark to treat the condition, which is known as Leber congenital amaurosis.

Spark went public in January and was valued at about $1.4 billion as of Friday’s close. Its product is now in the third and final stage of clinical trials before regulatory approval. The company’s ticker, “ONCE,” alludes to the promise to treating patients a single time.

Spark Trials

Spark has been following patients in earlier trials for two to four years and their vision improvements have lasted, said Chief Executive Officer Jeffrey Marrazzo.

“All these products are very different,” Marrazzo said in a telephone interview. “On the surface, they may look similar because they are all called gene therapy, but there’s a tremendous amount of devil in the details.” The various gene therapy approaches all use slightly different doses, components in the therapy and delivery methods.

In the Penn trial, the patients seemed to have better vision after treatment than before, even though the sensitivity had declined from peak levels.

Early Attempts

“It would be foolish to think we could get the treatment perfectly right in the first studies,” said Eric Pierce, director of the retinal degenerations service at Massachusetts Eye and Ear in Boston. Pierce worked on an early Spark trial and hasn’t been involved with any of the studies since.

“Maybe the people got treated too late in the disease course and the cells were already destined to die,” Pierce said. “Or maybe we didn’t have the dose of the gene therapy quite right yet. My expectation is with the right dose in the right setting, we would prevent further retinal cell loss. To me the most important message is we need to continue to improve these therapies.”

Between 90,000 and 180,000 people worldwide have Leber congenital amaurosis, a degenerative disease of the retina, the light-sensitive tissue at the back of the eye where images focus and are converted into electrical signals that are read by the brain. A mutation that leads to loss of function in the RPE65 gene is responsible for the disease in about 400 Americans and 9,000 people worldwide, Pierce said. That subset could benefit from the gene therapy.