The very first gene therapy is coming to the United States. The FDA approved the chimeric antigen receptor-T (CAR-T) treatment tisagenlecleucel (Kymriah) for the treatment of B-cell precursor acute lymphoblastic leukemia (ALL) in certain pediatric and young adult patients. The therapy is developed by Novartis.
"We are so proud to be part of this historic moment in cancer treatment and are deeply grateful to our researchers, collaborators, and the patients and families who participated in the Kymriah clinical program," Bruno Strigini, CEO of Novartis Oncology, said in a statement
. "As a breakthrough immunocellular therapy for children and young adults who desperately need new options, Kymriah truly embodies our mission to discover new ways to improve patient outcomes and the way cancer is treated."
CAR-T cell therapy represents a novel way to treat cancer: the treatment reengineers a patient’s own white blood cells to attack tumor cells.
“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, MD, said in a statement
. “New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses.”
Each dose of tisagenlecleucel is customized using the individual patient’s own T-cells, which are sent to a manufacturing center to be genetically modified. The new cells include the CAR gene, which directs T-cells to target and kill leukemia cells with the CD19 antigen on the surface. The cells are then infused back into the patient.
“Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for children and young adults with this serious disease,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “Not only does Kymriah provide these patients with a new treatment option where very limited options existed, but a treatment option that has shown promising remission and survival rates in clinical trials.”
At the beginning of July, the FDA’s Oncologic Drugs Advisory Committee had voted unanimously in favor
of tisagenlecleucel. A trial of 63 patients with relapsed or refractory B-cell precursor ALL reported an 83% remission rate within 3 months of treatment.
However, the treatment, while incredibly effective, has potentially severe side effects. CAR-T cell therapy can cause cytokine release syndrome (CRS), which is a response to the activation and proliferation of CAR-T cells. CRS causes high fever and flu-like symptoms. Tisagenlecleucel will also carry a boxed warning for neurological events. Both CRS and neurological events can be life-threatening.
In an interview
at last year’s Patient-Centered Oncology Care meeting, David L. Porter, MD, of the University of Pennsylvania Health System, explained that CRS is the most serious side effect of CAR-T cell therapy.
“It almost always starts with a fever and can escalate over time to very, very severe flu-like syndrome, with other complications,” he said. “Patients will have progressively high fevers, they can get as high as 104, 105 degrees and even higher. And as this progresses, patients develop myalgias and arthralgias, muscle aches and bone and joint aching that really has been quite severe in some cases."
The FDA also just approved a treatment for CRS. The agency expanded the approval for tocilizumab (Actemra) to treat CAR-T cell–induced CRS in patients 2 years or older.