Food and Drug Administration advisers on Wednesday enthusiastically endorsed a first-of-its-kind cancer treatment that uses patients' revved-up immune cells to fight the disease, concluding that the therapy's benefits for desperately ill children far outweigh its potentially dangerous side effects.
Timothy Cripe, a panel member who is an oncologist with Nationwide Children's Hospital in Columbus, Ohio, called the treatment the "most exciting thing I've seen in my lifetime."
Novartis, the drugmaker behind the CAR T-cell therapy, is seeking approval to use it for children and young adults whose leukaemia doesn't respond to traditional treatments - a group that numbers 600 or so patients a year in the US.
But the approach also is being tested for a range of diseases from non-Hodgkin lymphoma and multiple myeloma to solid tumours.
If cleared by the FDA, it would be the first gene therapy approved in the United States. But unlike traditional gene therapy, the new treatment doesn't replace disease-causing genes with healthy ones. Instead, it uses technology to reprogram immune cells called T cells to target and attack malignancies.
When a patient is treated under the Novartis process, T cells are extracted from a patient's blood, frozen and sent to the company's plant in Morris Plains, N.J. There, the cells are genetically modified to attack the cancer, expanded in number, refrozen and shipped back to the patient for infusion.
Once inside the body, the cells multiply exponentially and go hunting for the CD19 protein, which appears on a kind of white blood cell that can give rise to diseases, such as leukaemia and lymphoma. The turnaround time for manufacturing the therapy, called "vein-to-vein" time, will be an estimated 22 days, Novartis officials told the committee Wednesday.
From the start of Wednesday's meeting, committee members made clear that they were not concerned about the treatment's efficacy, which has been well established - 83 percent of patients went into remission in the pivotal Novartis trial.
Rather, the panel homed in on how to best to handle possible shot-term toxicities, as well as long-term safety risks and manufacturing quality.
Most patients in the Novartis study experienced something called cytokine release syndrome, which causes fever and flulike symptoms that can range from mild to extremely severe, said Stephan Grupp, an oncologist at the Children's Hospital of Philadelphia who led the Novartis trial.
Some patients in that study also had neurological problems, including seizures and delirium. But there were no cases of fatal brain swelling, as occurred in another company's trial, Grupp said.
To try to ensure safety, Novartis is limiting the therapy's availability to 30 to 35 medical centres where personnel have had extensive training with the treatment. The company also plans to post Novartis employees at hospitals using the therapy and to follow patients for up to 15 years.
During the committee meeting, hundreds of people packed the hearing room at FDA headquarters in Silver Spring, Md., including prominent scientists, such as Carl June of the University of Pennsylvania, who developed the treatment.
Though the FDA isn't required to follow the guidance of its advisory committees, it usually does.
David Maloney, medical director for cellular immunotherapy at Fred Hutchinson Cancer Research Center in Seattle, said he was elated that the field is moving forward.
"It represents a paradigm shift in treating cancers," said Maloney, who is extensively involved in CAR T-cell research but not in the Novartis product.
One of the big issues in CAR-T cell therapy - the cost, which analysts say could be in the hundreds of thousands of dollars - wasn't discussed because that is beyond the FDA's purview. Novartis hasn't released pricing information.
During the public comment portion of the hearing, Amy Kappen, whose 5-year-old daughter underwent CAR T-cell therapy in Philadelphia, called for approval. The treatment beat back her daughter's cancer and brought back "the sparkle" in her eyes. And while she died three months later, "our children deserve this chance," Kappen said.
For other parents, there were happier outcomes. Don McMahon, whose son Connor was treated at Duke Children's Hospital in North Carolina, said the therapy was far less debilitating than what he endured on standard chemotherapy during two relapses. The boy, an avid hockey player, is doing well now.
Thomas Whitehead, whose daughter was the first paediatric patient to receive the treatment, choked up while telling panel members about Emily's experience. She got CAR T-cell therapy when she was 6 and close to death from leukaemia. The treatment almost killed her, but she recovered and today is cancer free.
"If you want to see what a cure looks like for relapsed ALL [acute lymphoblastic leukaemia], she's standing right beside me," said Whitehead, his voice cracking.
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