The protocol involves removing a patient's white blood cells called T-cells, genetically modifying them, then infusing the newly transformed cells back into the patient's body following chemotherapy. Around 60 percent of them are young adults and children. Clinical trials of the medically advanced treatment were held in February 2016 by a group of scientists, when several dozen blood cancer patients, who barely had months to live, were administered the drug.
Explaining their vote, many advisors were effusive.
Dr. Manny Esquilin works at Driscoll Children's Hospital. Those so-called "risk mitigation" plans were one of the main concerns that the FDA, in documents released Monday, asked its advisors to consider.
Novartis believes it can turn around a finished CAR-T product 22 days from receipt of leukapheresed material to final packing and shipping.
"It is encouraging to see the FDA panel's recommendation and continued momentum behind this innovative therapy", said the Penn team's leader, Dr. Carl June. The prognosis for these patients is very poor, especially in patients who have relapsed more than two times or who relapse following allogenic stem-cell transplants. While patients on this engineered vehicle cell therapy have been repeatedly hit by potentially lethal cases of cytokine release syndrome and neurological toxicity with the threat of new malignancies, advisers were clearly willing to accept the risk in order to achieve the potential gains. "You have to be a long-term survivor to experience [long-term] toxicity", said Bruce Roth of the Washington University School of Medicine in St. Louis, MO.
The pediatric oncologists on the committee called Polanin out on her comments, saying her follow-up fears were unfounded when it comes to children.
Austin Schuetz, one of a handful of CAR-T patients to achieve multi-year remission of his cancer, requires biweekly infusions of immunoglobulin to replace B-cells wiped out by the engineered cancer-killing T-cells.
The treatment is complex and must be personalized for each patient.
Fatalities due to cerebral oedema have occurred with other CAR-T therapies however - notably Juno Therapeutics' JCAR015 which was discontinued in March and another candidate from Kite Pharma - and as a result the safety of CTL019 had been expected to come under close scrutiny.
"In those settings, the downstream effect [of triggering a secondary cancer] is conceivable", said Maziarz. The scientists also figured out how to embed a "suicide gene" that shuts the cells down if they start to trigger cytokine release syndrome-a risky inflammatory response that has raised concerns during CAR-T clinical trials conducted by Novartis and its rivals.
At the staring of this year, Novartis filed a BLA for CTL019 to the FDA.
Although the FDA is not bound to follow recommendations from its advisers when making decisions on treatments it usually does, and is due to make a decision on CTL019 in September following a six-month priority review.
Novartis is also testing the drug in diffuse large b-cell Lymphoma (DLBCL), the most common form of non-Hodgkin lymphoma, as is Kite.
"This can be a challenging issue given the complex and labor-intensive manufacturing processes involved with making a vehicle T-cell product", the FDA staffers added.
But CAR-T's potential goes far beyond leukemia.
Also benefiting from the decision was Oxford Biomedica, Novartis' lentivirus manufacturer, which was up as much as 10% this morning. The immune cells from the patient's blood are being reprogrammed to focus on cancer cells and completely destroy them without doing any damage to the healthy cells that are around it. These are in patients that have failed everything.
The drug uses a new technology known as CAR-T, or chimeric antigen receptor T-cell therapy, which harnesses the body's own immune cells to recognise and attack malignant cells.
Alex Lash is Xconomy's National Biotech Editor.