A new kind of cancer treatment that uses genetically engineered cells from a patient's immune system to attack their cancer easily cleared a crucial hurdle Wednesday.
A Food and Drug Administration advisory committee unanimously recommended that the agency approve this "living drug" approach for children and young adults who are fighting a common form of leukemia. The agency doesn't have to follow the committee's recommendation but usually does.
The treatment takes cells from a patient's body, modifies the genes, and then reinfuses those modified cells back into the person who has cancer. If the agency approves, it would mark the first time the FDA has approved anything considered to be a "gene therapy product."
The treatment is part of one of the most important developments in cancer research in decades — finding ways to harness the body's own immune system to fight cancer. And while it has generated much hope, there are some concerns about its safety over the long term — and its cost.
Even so, several of the committee members were unusually enthusiastic in explaining their 10-0 vote recommending approval.
"This is the most exciting thing I've seen in my lifetime," said Dr. Timothy Cripe, an oncologist at the Nationwide Children's Hospital in Columbus, Ohio.
"This is a major advance and is ushering in a new era in treating children," agreed Dr. Malcolm Smith, associate branch chief for pediatric oncology at the National Cancer Institute.
For years, scientists have tried to use drugs that stimulate the immune system to fight cancer, and have had only modest success.
In recent years, however, scientists developed a new generation of "immunotherapy" drugs that have produced impressive results for a wide range of cancers by unleashing the body's natural defense system.
The new treatment is known as CAR-T cell immunotherapy. It works by removing key immune system cells known as T cells from the patient so scientists can genetically modify them to seek out and attack only cancer cells. That's why some scientists refer to this as a "living drug."
Doctors then infuse millions of the genetically modified T cells back into the patient's body so they can try to obliterate the cancer cells and hopefully leave healthy tissue unscathed.
"It's truly a paradigm shift," said Dr. David Lebwohl, who heads the CAR-T Franchise Global Program at the drug company Novartis, which is seeking the FDA's approval for the treatment. "It represents a new hope for patients."
The drug endorsed by the advisory panel is known as CTL019 or tisagenlecleucel. It was developed to treat children and young adults ages 3 to 25 who have relapsed after undergoing standard treatment for B cell acute lymphoblastic leukemia, which is the most common childhood cancer in the United States.
While this blood cell cancer can be highly curable, some patients fail to respond to standard treatments; and a significant proportion of patients experience relapses that don't respond to follow-up therapies.
"There is a major unmet medical need for treatment options" for these patients, Dr. Stephen Hunger, who helped study at the Children's Hospital of Philadelphia, told the committee.
In the main study that the company submitted as evidence in seeking FDA approval, doctors at 25 sites in 11 countries administered the treatment to 88 patients. The patients, ages 3 to 23, had failed standard treatment or experienced relapses and failed to respond to follow-up standard treatment. CTL019 produced remissions in 83 percent of patients, the company told the committee.
"This product has been shown to result in a high rate of response," Lebwohl said.
Still, while those results are encouraging, the approach has raised concerns.
The treatment can produce a life-threatening adverse reaction known as a "cytokine release syndrome," in which the immune system attacks vital organs. In the past, a handful of patients who were getting similar treatments developed by other companies died from serious brain swelling.
Although those sorts of complications did occur in some patients receiving CTL019, the patients recovered and there were no fatalities, the company says.
There are also concerns about possible long-term complications. Scientists use a virus to make the genetic changes in the T cells, raising fears about possible long-term side effects.
Because of the safety concerns, the company plans to continue to follow the medical progress of patients receiving the treatment. The company is also planning to initially make the treatment available only at about 30 to 35 hospitals that have had the necessary training and expertise to produce and administer the complex treatment.
Another big concern is the cost. While Novartis will not estimate the price it will ultimately put on the treatment, some industry analysts project it will cost $500,000 per infusion.
Nevertheless, during a public comment period several family members of children who benefited from the treatment in its experimental phase have made emotional appeals to the committee to recommend approval.
"I'm happy most of all for the patients who will benefit from this therapy," said Dr. Carl June of the University of Pennsylvania Perelman School of Medicine, who developed the therapy.
KELLY MCEVERS, HOST:
Cancer patients are a step closer to an entirely new way to fight their disease. It's something scientists call a living drug. Today a pharmaceutical company cleared a crucial hurdle toward offering the treatment widely to patients for the first time, starting with kids who have leukemia. NPR health correspondent Rob Stein is with us now to talk about this. And Rob, tell us what happened today.
ROB STEIN, BYLINE: Yeah, hi, Kelly. So a panel of outside experts assembled by the Food and Drug Administration spent the whole day reviewing an application from the drug company Novartis. Novartis wants the FDA to let the company start selling this treatment for kids and young adults with leukemia who've run out of other options. And this would be the first time the FDA has approved this entirely new way to fight cancer. In fact the FDA says it would be the first time they were approving anything that they would call a gene therapy product.
MCEVERS: What is that? How does it work? What makes it unique?
STEIN: Yeah, so you - we all know how we usually treat cancer. We either, you know, cut it out with surgery, or we poison it with chemotherapy or radiation.
STEIN: And this is part of the hot new thing in cancer research, which is using the body's natural defense system, our own immune system, to kill cancer cells. Scientists - you know, in recent years, they've come up with some new drugs that can trigger the immune system to attack tumors. What this is is scientists are using genetic engineering to create tailor-made living cells to attack tumors. And that's why scientists are calling this a living drug.
MCEVERS: How do they do it?
STEIN: Well, it's really interesting and kind of complicated. So what doctors do is they remove very specific immune systems from people's bodies - known as T cells from their blood. And they take the cells, take them back to their lab. And they use genetic engineering to reprogram the genes in the cells to turn them into what you can kind of think of as like attack drones or laser-guided missiles that zero in on their cancer cells. And then the doctors - they infuse millions of these genetically modified smart bombs back into the patients' bodies so they can obliterate the cancer and hopefully leave the healthy cells, you know, unscathed.
MCEVERS: And has it worked?
STEIN: So far it looks really promising. You know, the company tested this on dozens of kids and young adults who had a type of leukemia called B-cell acute lymphoblastic leukemia. It's the most common form of cancer among kids in the United States. And these patients - either they hadn't responded to the traditional therapies, or they'd had a relapse and really had run out of any other options. And when they gave them this treatment, 83 percent of the patients went into remission. So an overwhelming majority of the patients went into remission. And this isn't the only cancer it seems to be working on. It seems to be working on some other cancers as well.
MCEVERS: Are there any dangers or side effects to the treatment?
STEIN: Yeah, you know, that is a concern here. This treatment can cause some pretty severe and potentially even fatal side effects. It can cause the immune system to sort of go into overdrive and attack the patients' bodies. Doctors call this a cytokine storm. And it can cause, you know, sometimes a dangerous swelling in the brain. In fact there were a handful of patients who died from this brain swelling when they were in a study sponsored by another drug company, a different version of this.
And so there are also some concerns about long-term side effects. The big concern is they genetically engineer these cells using a virus. And so so far, that all looks fine, but patients haven't really been involved that long. So there's some concern that, you know, we don't know what could happen in the future. And I guess the final big thing is this is not cheap. You know, it's a very complicated treatment to create, so it's going to cost a lot. I - you know, doctors have to tailor-make each treatment for each patient.
STEIN: So we're talking hundreds of thousands of dollars for each infusion.
MCEVERS: Quickly, what happens next?
STEIN: So the FDA doesn't have to follow the advice of its advisers, but it usually does. And there are some other cancers - other companies developing similar therapies that are waiting in the wings to try to get their drugs to prove true.
MCEVERS: NPR health correspondent Rob Stein, thank you.
STEIN: Oh, sure.
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