Spark Therapeutics, a Philadelphia company at the forefront of gene-therapy research, reported Monday that patients in its most important clinical trial had some eyesight restored after treatment by Spark's product.
For now, the name of the product is SPK-RPE65, which - along with Spark itself - was spun out of decades of research led by Kathy High at the Children's Hospital of Philadelphia, the largest shareholder in the publicly traded company.
"We saw substantial restoration of vision in patients who were progressing toward complete blindness," Albert M. Maguire, principal investigator in the trial and an ophthalmologist at Penn's Perelman School of Medicine, said in a statement.
Gene therapy involves injecting genetic material into a person's cells to correct a mutation in hopes of restoring normal function.
Spark's study involved 31 patients who had a genetic mutation in the retina called Leber congenital amaurosis that can lead to blindness or a condition sometimes referred to as night blindness, in which vision is severely restricted. None of the trial participants, ranging in age from 4 to 44, was completely blind and none had perfect vision.
The primary test involved measuring improvement they made after one year after the injection in navigating a course with black arrows on a white floor, with steps and other obstacles. The main variable was how much light - seven levels, from a bright office to a moonless summer night - a participant needed to get a passing grade on that course. Of the 31 in the study, 10 served as the control group and did not receive any injection. However, when the test was done, nine of the 10 were allowed to have the treatment.
Spark did not release the full data set, which researchers, financial analysts, and the Food and Drug Administration will want to see. But CEO Jeff Marrazzo said "two-thirds" of the people receiving the treatment improved to the maximum level. The others improved but not to a statistically significant level. The trial did not meet one of three secondary targets, a test of visual acuity, which is basically measured by the ability to read an eye chart.
"This is landmark moment in our field," said Srinivas Sadda, president and chief scientific officer at UCLA's Doheny Eye Institute, who was not involved in the study and said he has no financial ties to Spark. "Retinal degeneration in many cases has been essentially untreatable."
Genetic material can be delivered to a cell using a carrier known as a "vector." The most common types of vectors are modified viruses. The hope is that new genes and cells will then reproduce in ways that cure the problem forever, which would differ dramatically from most drugs that simply treat disease. But the industry is in its infancy and deadly mistakes were made in the past, including the 1999 death of Jesse Gelsinger during a clinical trial at the University of Pennsylvania.
Spark said Monday there "were no serious adverse events" in the phase 3 trial, which usually proceeds an application to the FDA. Spark said about 3,500 people in the United States and five European countries have the specific genetic condition that was tested. Like others, Spark hopes this is a step in using gene therapy to treat other diseases and it has a trial underway to treat a form of hemophilia.
Gislin Dagnelie, a researcher in the Wilmer Eye Institute at Johns Hopkins University, said the results are encouraging, especially for children with the condition who faced "a pretty grim prognosis."
Dagnelie said, "There is definitely a question about how effective it will be over the long term."
No gene-therapy product has been approved by the FDA. (One was approved by the European Medicines Agency in 2012.) Spark said it plans to apply in 2016 for FDA approval.
Financial analysts have told clients that they expect Spark to charge $1 million for the treatment. Spark's Marrazzo said Monday it is too early to set a price, but also that he hopes the treatment and price can prompt new models of paying for cures instead of lifetime treatments. Spark chose the stock ticker symbol ONCE to signify its hope of a one-time treatment, but that also might require payments over time. (The share price rose $9.09 in Nasdaq trading to close at $53.02 on Monday.)
"The larger question is not price but changes to the payment system," Marrazzo said. "We need to think differently about payment incentives for products that involve a one-time treatment."
Gordon Gund certainly hopes one-time cures are the result. An investor and owner of sports teams, Gund, 75, lost his sight at age 31, and channeled his money to the Foundation Fighting Blindness. It gave seed money to Spark, though it does not own stock today. Gund said he won't be cured, but he hopes Monday's test results signal others will be.
"Our interest," Gund said of his foundation, "is in eventually going out of business."