CAR-T drugs like tisagenlecleucel are made by removing immune cells from a patient, genetically modifying them using a virus and putting them back into the patient. The virus creates a new cell receptor -- which is, in Novartis' case, part mouse -- that targets another receptor on the cancer cells: CD19. This modification of the cells causes them to attack the cancer cells.
By modifying immune cell DNA, this method could, in theory, lead to other cancers -- a longtime concern for gene therapy. But researchers have found no cases of this happening with the CAR-T treatment so far. Brody said it could take decades to conclusively say this does not happen.
"We've never seen this theoretical thing," Brody said, arguing that the chance of any adverse event happening is certainly smaller than the certain death of relapsed cancer. "It's not an opinion. This is straightforward numbers."
Brody said personalized immunotherapy treatments like this one require that patients use their own immune cells because they would "almost never (find) a match" in an off-the-shelf product.
"You can put someone else's red blood cells into you," he said. "You can almost never put someone's (immune) cells into you."
"This therapy will no doubt save the lives of many children and young adults who have had no other effective therapy," said Dr. John Maris, a pediatric oncologist at The Children's Hospital of Philadelphia and leader of the SU2C-St. Baldrick's Pediatric Cancer Dream Team.
"This is truly a turning point in the management of this disease."
Kite Pharmaceuticals has another CAR-T drug up for FDA priority review for the treatment of lymphoma.
The Novartis drug would not be the only FDA-approved drug to target CD19; Amgen's blinatumomab treats ALL using this target, but "it's overall not quite as good" as the data coming out of the Novartis trials, Brody said.
The FDA previously approved Amgen's T-VEC
, which injects a modified herpesvirus into melanoma cells, causing them to rupture. The same goes for personalized immunotherapy: Dendreon's Provenge
was FDA-approved to treat prostate cancer in 2010, for example.
Novartis refers to the drug as immunotherapy, not gene therapy. The FDA, however, would classify it as gene therapy.
The FDA does not have to follow the recommendation of their advisory committees, although it often does. The agency declined to comment on when it would issue a final decision on the committee's recommendation. Novartis expects the FDA to make a final decision by October but declined to comment on