A Food and Drug Administration panel opened a new era in medicine Wednesday, unanimously recommending that the agency approve the first treatment that genetically alters a patient's own cells to fight leukemia, transforming them into what scientists call "a living drug" that powerfully bolsters the immune system to shut down the disease.
If the FDA accepts the recommendation, which is likely, the treatment will be the first gene therapy to reach the market. Others are expected: Researchers and drug companies have been engaged in intense competition for decades to reach this milestone. Novartis is now poised to be the first, and it is working on similar types of treatments for another type of leukemia, as well as multiple myeloma and an aggressive brain tumor.
To use the technique, a separate treatment must be created for each patient — their cells removed at an approved medical center, frozen, shipped to a Novartis plant for thawing and processing, frozen again and shipped back to the treatment center. A single dose of the resulting product has brought long remissions, and possibly cures, to scores of patients in studies who faced death because every other treatment had failed. The panel recommended approving the treatment for B-cell acute lymphoblastic leukemia that has resisted treatment, or relapsed, in children and young adults ages 3 to 25.
One of those patients, Emily Whitehead, now 12 and the first child given the altered cells, was at the meeting of the panel with her parents to advocate approval of the drug that saved her life. In 2012, as a 6-year-old, she was treated in a study at the Children's Hospital of Philadelphia. Severe side effects — raging fever, crashing blood pressure, lung congestion — nearly killed her. But she emerged cancer-free, and has remained so.
"We believe that when this treatment is approved it will save thousands of children's lives around the world," Emily's father, Tom Whitehead, told the panel. "I hope that someday all of you on the advisory committee can tell your families for generations that you were part of the process that ended the use of toxic treatments like chemotherapy and radiation as standard treatment, and turned blood cancers into a treatable disease that even after relapse most people survive."
At the meeting, the panel of experts did not question the lifesaving potential of the treatment in hopeless cases. But they raised concerns about potentially life-threatening side-effects — short-term worries about acute reactions like those Emily experienced, and longer-term worries about whether the infused cells could, years later, cause secondary cancers or other problems. So far, no such long-term problems have been detected, but not enough time has passed to rule them out.
Another parent at the meeting, Don McMahon, described his son Connor's grueling 12 years with severe and relapsing leukemia, which started when he was 3. McMahon displayed painful photographs of Connor, bald and intubated during treatment. And he added that chemotherapy had left his son infertile. A year ago, the family was preparing for a bone-marrow transplant when they learned about T-cell treatment. Connor underwent the cell treatment at Duke University, and he has since returned to playing hockey. Compared with standard treatment, which required dozens of spinal taps and painful bone-marrow tests, the T-cell treatment was far easier to tolerate, McMahon said, and he urged the panel to vote for approval.
The treatment was developed by researchers at the University of Pennsylvania and licensed to Novartis.
Use will not be widespread at first, because the disease is not common. It affects only 5,000 people a year, about 60 percent of them children and young adults. Most children are cured with standard treatments, but in 15 percent of the cases — like Emily's and Connor's — the disease does not respond, or it relapses.
Analysts predict that these individualized treatments could cost more than $300,000, but a spokesman for Novartis declined to specify a price.
Because the treatment is complex and patients need expert care to manage the side effects, Novartis will initially limit its use to 30 or 35 medical centers where staff will be trained and approved to administer it, the company said.
As to whether the treatment, known as CTL019, will be available in other countries, a Novartis spokeswoman said by email: "Should CTL019 receive approval in the U.S., it will be the decision of the centers whether to receive international patients. We are working on bringing CTL019 to other countries around the world." She added that the company would file for approvals in the European Union later this year.
The treatment requires removing millions of a patient's T-cells — a type of white blood cell — and genetically engineering them to kill cancer cells. The technique employs a disabled form of HIV, the virus that causes AIDS, to carry new genetic material into the T-cells to reprogram them. The process turbocharges the T-cells to attack B-cells, a normal part of the immune system that turn malignant in leukemia. The T-cells home in on a protein called CD-19 that is found on the surface of most B-cells.
The altered T-cells — called chimeric antigen receptor cells — are then dripped back into the patient's veins, where they multiply and start fighting the cancer.
Dr. Carl H. June, a leader of the University of Pennsylvania team that developed the treatment, calls the turbocharged cells "serial killers." A single one can destroy up to 100,000 cancer cells.
In studies, re-engineering cells for treatment sometimes took four months, and some patients were so sick that they died before their cells came back. At the meeting, Novartis said the turnaround time was now down to 22 days. The company also described bar-coding and other procedures used to keep from mixing up samples once the treatment is conducted on a bigger scale.