The therapy, Yescarta (axicabtagene ciloleucel
), is intended for adult patients with certain types of large B-cell lymphoma after other treatments fail.
, which account for about 4% of all cancers in the United States, are malignancies that begin in certain cells of the immune system. An estimated 72,000 new cases are diagnosed each year in the US.
Diffuse large B-cell lymphoma, which is the most common form of non-Hodgkin lymphoma, represents about one in three newly diagnosed cases.
Currently, up to half of all patients
with large B-cell lymphoma relapse or become resistant to treatments, which may include chemotherapy, stem cell transplants, and immunotherapy.
Dr. Scott Gottlieb, commissioner of the FDA, noted in a statement
announcing the approval Wednesday, how gene therapy has "gone from being a promising concept to a practical solution" for treating deadly forms of cancer in just several decades. He called the approval a "milestone."
The new drug is made by California-based Kite, a subsidiary of drug giant Gilead Sciences that develops chimeric antigen receptor and T-cell receptor (CAR-T) cell therapies. These new treatments use a patient's own T-cells to seek and destroy cancer cells.
To make each dose of Yescarta, the patient's T-cells -- a type of white blood cell -- are collected and then genetically modified to include a new gene that targets and kills the cancer cells.
The engineered cells are then infused back into the patient.
A clinical trial involving more than 100 adult patients established the safety and efficacy of Yescarta. After treatment with the drug, 51% of patients experienced a complete remission of their cancer.
However, treatment with Yescarta can cause severe side effects. These can include life-endangering neurologic toxicities -- with symptoms of headache, limb numbness, loss of memory, vision, and/or intellect -- and cytokine release syndrome, when a storm of immune proteins called cytokines are released into a patient's circulatory system. This syndrome causes symptoms such as fever, nausea, chills, tachycardia, and headache.
Other potential side effects include serious infections and a weakened immune system.
Because of these risks, the FDA has approved Yescarta with a risk evaluation and mitigation strategy (REMS), which includes a requirement that hospitals and clinics be specially certified before dispensing the therapy.
Michaela Almgren, a clinical assistant professor at University of South Carolina College of Pharmacy, pointed out this will not be available in just any facility due to the many challenges surrounding extraction of a patient's T-cells, alteration of genes, and reengineering the cells in sufficient quantity. Almgren was not involved in development of the new therapy.
"It is not just something that the hospital or treatment center can order and then put on the shelf," said Almgren.
The FDA is also requiring that Kite continue to conduct observational studies of patients treated with Yescarta. In addition, the packaging must include a warning to alert patients of the risks.
Noting the FDA's commitment to "supporting and helping expedite" the development of gene therapies, Gottlieb said, "we will soon release a comprehensive policy to address how we plan to support the development of cell-based regenerative medicine. That policy will also clarify how we will apply our expedited programs to breakthrough products that use CAR-T cells and other gene therapies."
The FDA is currently considering an unrelated gene therapy to treat an inherited form of blindness.
Dr. Arie Belldegrun, founder of Kite, recognized "the FDA for their ability to embrace and support transformational new technologies that treat life-threatening illnesses."
"We believe this is only the beginning for CAR-T therapies," said Belldegrun in a statement
On August 30, the FDA approved its first cell-based gene therapy for the treatment of advanced leukemia in children and young adults.
Almgren said the approval of Yescarta is "certainly very exciting." Using the patient's immune system to attack cancer cells can be very effective for treating malignancies and keeping cancer in remission, she noted.
"I believe this treatment approach brings hope to many patients, but one thing to consider is cost," said Almgren. The treatment is expensive -- priced at $373,000 according to Gilead.
Dr. David Maloney, medical director of cellular immunotherapy at Fred Hutchinson Cancer Research Center, helped develop the therapy and said the FDA's second approval of a CAR-T cell therapy "validates the revolution underway in the field of cellular immunotherapy."
The FDA decision opens the door for a new gene therapy to treat adults with aggressive lymphoma, noted Maloney. He said, "There will likely be thousands of lives saved in the next few years because of it."