Calling its endorsement a "historic action," the U.S. Food and Drug Administration on Wednesday approved the world's first genetically engineered immune therapy, Novartis Pharmaceuticals' T-cell treatment for pediatric leukemia.
The technology behind Novartis' personalized drug, called Kymriah, or tisagenlecleucel, was developed at the University of Pennsylvania by a team led by gene therapy pioneer Carl June. Each patient's immune system T cells are removed, programmed to attack acute lymphoblastic leukemia cells, then returned to the patient.
The therapy showed unparalleled effectiveness, putting more than 80 percent of terminally ill youths into remission in clinical tests at Children's Hospital of Philadelphia beginning in 2012, and in a pivotal study of 68 children at 25 medical centers around the world.
"We're entering a new frontier in medical innovation with the ability to reprogram a patient's own cells to attack a deadly cancer," FDA Commissioner Scott Gottlieb said in a news release. "New technologies such as gene and cell therapies hold out the potential to transform medicine."
Novartis announced a hefty price tag — $475,000 for the onetime treatment — but said it is working with private insurers and the federal Centers for Medicaid and Medicare to develop a novel payment policy based on patient outcomes.
"There will be no charge for the therapy if the patient doesn't respond within the first month after treatment," Novartis CEO Joseph Jimenez said during a media call.
Whether the therapy works or not, patients' insurance will have to cover the costs of the lengthy hospitalization involved in preparing for, and recovering from, the T-cell therapy.
The company also said it will help uninsured patients get access, and will offer eligible families assistance with travel costs, because the treatment will be available only at select hospitals.
Kymriah is approved for patients up to age 25 with B-cell acute lymphoblastic leukemia who have relapsed at least once with conventional treatment — chemotherapy, radiation, and bone-marrow transplant.
While Kymriah has not shown the kind of long-term toxicities that make conventional therapy such a double-edged sword for children, it typically causes severe, temporary side effects within days of infusion, including fevers, low blood pressure, and neurological problems. The FDA expanded its previous approval of a rheumatoid arthritis drug, Actemra, to help manage these side effects.
The market for the breakthrough drug is relatively small; about 600 children a year in the United States may be candidates. Novartis is also seeking approval from the European Medicines Agency.
But the promise of T-cell therapy is believed to be vast. Novartis and other companies are racing to develop T-cell therapies for other blood disorders, as well as for solid-tumor cancers, which have so far defied this immune-boosting approach.
The Kymriah approval came just over three months after the first patient to receive it, 12-year-old Emily Whitehead of Philipsburg, Pa., celebrated five years cancer-free in May.
The T-cell therapy was first tested at Penn in 2010, in three adults with advanced chronic lymphocytic leukemia. It was so effective that Novartis partnered with Penn in 2012 to research and commercialize bioengineered T-cell therapies, starting with Kymriah.
Although the manufacturing and delivery of the living drug poses huge challenges, Novartis' global clinical trial proved the feat can be achieved. Each patient's T cells will be collected at a hospital certified to have the necessary expertise. The cells will be frozen and shipped to Novartis' plant in Morris Plains, N.J., where they will be bioengineered and multiplied, refrozen, and shipped back to be infused into the patient.
Novartis expects to have 25 hospitals certified within a month, and 32 by the end of the year. Patients will be followed for 15 years to evaluate the long-term safety of Kymriah.