BOSTON — The trouble had started over a decade ago, when the Hogans noticed something wasn’t right with their son Jack. As a baby, he would spend hours staring into the lights in his nursery. Later, he sometimes walked into walls or fell down the stairs. When they asked him to pick up his toys, he wouldn’t — not because he didn’t want to, it turned out, but because he didn’t have the peripheral vision with which to see them strewn across the floor. They soon found out he was night-blind, too.
This past Sunday, his parents drove him five hours from New Jersey to Boston in the hope that he might regain some of his vision. On Tuesday, he was to be the first person in the U.S. to receive a gene therapy for a rare inherited disease since the treatment had hit the market.
Jack is 13 now — a smiley kid with blond hair and taped-together, blue-rimmed glasses — and his family had been anticipating this moment for years. They’d monitored the painstaking progression of the clinical trial. They’d recorded the evening news on the day last December when the drug got approved. And they’d watched as the price was announced at $850,000 for both eyes — a record price so high that Spark Therapeutics worked out a way for insurers to pay in installments, as if the medication were a fancy car.
Late last week, everything seemed set. The surgery to inject the treatment was one of several scheduled across the country on Tuesday and soon after. For both the doctors and the families involved, the week had brought a mix of stress and relief.
But for Dr. Jason Comander, Jack’s surgeon at Mass. Eye and Ear, there was one final hitch, even before he stepped into the operating room.
On the day the vials were supposed to be shipped from Philadelphia to Boston, he got a call about the family’s insurance: The company needed evidence showing that the specific genetic mutation in each of Jack’s eyes was the cause of his visual impairment.
Comander started to panic. He’s usually pretty unflappable, accustomed to carefully maneuvering instruments in through the whites of people’s eyes. While there is plenty of research on mutations in the RPE65 gene generally, not much of it had focused on the specific genetic error Jack had in one of his two copies of that gene. Without that kind of proof, the caller seemed to imply, the vials wouldn’t be shipped.
The surgery was a few days away. “I left a message for our genetic counselor and said, ‘This is as close to a genetic testing emergency as you’re going to get, please help,’” Comander told STAT.
It was a high-profile procedure, and families around the country were already nervous enough. The clinical trial results had been good — and in some cases, almost miraculous, with patients able to see the stars for the first time. Still parents couldn’t be absolutely sure that the one-time treatment would work. And no matter how dazzling the possibilities, any parent would be anxious about a surgery that involved digging into the depths of their child’s eye.
Their kids are part of a relatively small number born with defective versions of the RPE65 gene, which means they aren’t able to properly produce a protein that helps the eyes process light. Some can see during the day, with vision shrinking to nothing after dusk; others are legally blind.
The treatment, developed after decades of research, is called Luxturna, and it is sometimes referred to as the first “true” gene therapy to be approved by the Food and Drug Administration. Cancer treatments such as Kymriah and Yescarta are also sometimes described as a kind of gene therapy, but they involve removing a patient’s cells, genetically modifying them, and sending them back into the body to fight the disease. With Luxturna, a doctor injects a virus underneath the retina, where it delivers a healthy, lab-grown copy of the RPE65 gene into the cells. If the therapy works for these patients, it could help restore some of the images they have been missing.