Gene therapy, which has had a roller-coaster history of high hopes and devastating disappointments, took an important step forward Thursday.
A Food and Drug Administration advisory committee endorsed the first gene therapy for an inherited disorder — a rare condition that causes a progressive form of blindness that usually starts in childhood.
The recommendation came in a unanimous 16-0 vote after a daylong hearing that included emotional testimonials by doctors, parents of children blinded by the disease and from children and young adults helped by the treatment.
"Before surgery, my vision was dark. It was like sunglasses over my eyes while looking through a little tunnel," 18-year-old Misty Lovelace of Kentucky told the committee. "I can honestly say my biggest dream came true when I got my sight. I would never give it up for anything. It was truly a miracle."
Several young people described being able to ride bicycles, play baseball, see their parents' faces, read, write and venture out of their homes alone at night for the first time.
"I've been able to see things that I've never seen before, like stars, fireworks, and even the moon," Christian Guardino, 17, of Long Island, N.Y., told the committee. "I will forever be grateful for receiving gene therapy."
The FDA isn't obligated to follow the recommendations of its advisory committees, but it usually does.
If the treatment is approved, one concern is cost. Some analysts have speculated it could cost hundreds of thousands of dollars to treat each eye, meaning the cost for each patient could approach $1 million.
Spark Therapeutics of Philadelphia, which developed the treatment, hasn't said how much the company would charge. But the company has said it would help patients get access to the treatment.
Despite the likely steep price tag, the panel's endorsement was welcomed by scientists working in the field.
"It's one of the most exciting things for our field in recent memory," says Paul Yang, an assistant professor of ophthalmology at the Oregon Health and Science University who wasn't involved in developing or testing the treatment.
"This would be the first approved treatment of any sort for this condition and the first approved gene therapy treatment for the eye, in general," Yang says. "So, on multiple fronts, it's a first and ushers in a new era of gene therapy."
Ever since scientists began to unravel the genetic causes of diseases, doctors have dreamed of treating them by fixing defective genes or giving patients new, healthy genes. But those hopes dimmed when early attempts failed and sometimes even resulted in the deaths of volunteers in early studies.
But the field may have finally reached a turning point. The FDA recently approved the first so-called gene therapy product, which uses genetically modified cells from the immune system to treat a form of leukemia. And last week, scientists reported using gene therapy to successfully treat patients suffering from cerebral adrenoleukodystrophy, or ALD, a rare, fatal brain disease portrayed in the film Lorenzo's Oil. Researchers are also testing gene therapy for other causes of blindness and blood disorders such as sickle cell disease.
The gene therapy endorsed by the committee Thursday was developed for RPE65-mutation associated retinal dystrophy, which is caused by a defective gene that damages cells in the retina. About 6,000 people have the disease worldwide, including 1,000 to 2,000 people in the United States.
The treatment, which is called voretigene neparvovec, involves a genetically modified version of a harmless virus. The virus is modified to carry a healthy version of the gene into the retina. Doctors inject billions of modified viruses into both of a patient's eyes.
In a study involving 29 patients, ages 4 to 44, the treatment appeared to be safe and effective. More than 90 percent of the treated patients showed at least some improvement in their vision when tested in a specially designed obstacle course. The improvement often began within days of the treatment.
"Many went from being legally blind to not being legally blind," said Albert Maguire, a professor of ophthalmology who led the study at the University of Pennsylvania, in an interview before the hearing.
The improvement varied from patient to patient, and none of the patients regained normal vision. But some had a significant increase in their ability to see, especially at night or in dim light, which is a major problem for patients with this condition.
"What I saw in the clinic was remarkable," Maguire told the committee. "Most patients became sure of themselves and pushed aside their guides. Rarely did I see a cane after treatment."
That was the case of Allison Corona, who's now 25 and lives in Glen Head, N.Y. She underwent the treatment five years ago as part of the study.
"My light perception has improved tremendously," Corona said during an interview before the hearing. "It's been life-changing. I am able to see so much better. I am so much more independent than what I was. It is so much better."
The patients have been followed for more than three years, and the effects appear to be lasting. "We have yet to see deterioration," Maguire says. "So far the improvement is sustained."
The injections themselves did cause complications in a few patients, such as a serious infection that resulted in permanent damage, and a dangerous increase in pressure in the eye. But there were no adverse reactions or any signs of problems associated with the gene therapy itself, the researchers reported.
While this disease is rare, the same approach could work for similar forms of genetic eye disease, Maguire says."There are a lot of retinal diseases like this, and if you added them together it's a big thing because they are all incurable."
If approved, the treatment would be marketed under the name Luxturna.
KELLY MCEVERS, HOST:
The dream of gene therapy took a big step forward today. A Food and Drug Administration advisory committee unanimously endorsed the first gene therapy for an inherited disorder. NPR health correspondent Rob Stein is with us now for the details. Hey, Rob.
ROB STEIN, BYLINE: Oh, hey there.
MCEVERS: So let's start by talking about the disease that this gene therapy would be used to treat. Tell us about it.
STEIN: Yeah, it's called retinal dystrophy. And it's a genetic disorder that causes progressive damage to the retina in the eye often starting in childhood and slowly leading to blindness. It's a pretty rare disease. There are maybe about 6,000 cases worldwide. A couple of thousand of those are in the United States.
MCEVERS: And so these 6,000 people could benefit from gene therapy. But what does that mean, gene therapy? How does it work?
STEIN: Yeah, it's pretty interesting stuff, Kelly. So what they did is scientists took a harmless virus, and they genetically engineered it to make a - to make it into kind of like a delivery drone to ferry a healthy version of the gene that's defective in this disease into patients' eyes. And then doctors inject billions of these genetically modified viruses into the patients' eyes. That gets the healthy gene into the retina, where it pumps out a healthy version of an enzyme that's needed for healthy vision.
MCEVERS: How well does it work?
STEIN: Well, so far it looks like it's working really well, you know? Now, it's only been tested on a couple of dozen patients so far, but it seemed like almost all of them benefited to some degree, or at least most of them did. For some of them, it was just kind of modest improvement. But for others, their vision started to improve within days of getting these injections.
And it improved pretty dramatically within a year. You know, they went from being legally blind - you know, they were unable to walk around without a cane or someone guiding them. And they were - a lot of them were totally trapped in their houses at night because they had terrible night vision. And then they suddenly could do things they could never do before.
Like, during today's hearings, some kids got up, and some teenagers described that they could for the first time do things like read, ride a bike, play sports, play baseball, see their parents' faces. You know, and one young man got up and said for the first time, he could go out at night, look up at the sky and see the stars and the moon. It was pretty dramatic, and it really opened up the world for a lot of these people.
MCEVERS: Wow. So an FDA committee endorses it. So does that mean that it is safe? I mean, are there side effects? And how long might those last?
STEIN: Yeah, yeah. So far it seems pretty safe. You know, there sometimes were some complications that occurred from the procedure of injecting something into the eye, the physical procedure. But so far there are no signs at all that the gene therapy itself was dangerous, that injecting a gene into the eye caused any significant complications.
Now, so far it does seem to be lasting, but that's a big question. How long will it continue to last? These patients have been followed for maybe three years, and it's continuing to work. But they're going to have to follow these patients for longer to be sure.
MCEVERS: Any idea of how much it would cost?
STEIN: So that's a big question. There's a lot of speculations by analysts that it could be pretty expensive. You know, any - some of the newer treatments that have been approved recently have cost hundreds of thousands of dollars. And so you can imagine if this costs, you know, $400,000 or $500,000 for each eye, we're talking about potentially a million-dollar treatment. But the company hasn't said yet what it's going to charge for this product.
MCEVERS: What does today's news say about where gene therapy stands overall?
STEIN: You know, scientists and doctors have been dreaming about doing gene therapy for decades, but early on, there were some real setbacks. Some patients died, and people thought it was never going to happen. But recently there was another treatment approved, and it looks pretty promising for a number of conditions. So it looks like we might be at a turning point here.
MCEVERS: NPR health correspondent Rob Stein, thanks a lot.
STEIN: Oh, sure. Nice to be here. Transcript provided by NPR, Copyright NPR.