First CAR-T Therapy Approved for B-cell Acute Lymphoblastic Leukemia (ALL)
August 30, 2017 – The U.S. FDA has approved Kymriah™ (tisagenlecleucel), developed by Novartis, to treat patients under 25 years of age who have B-cell acute lymphoblastic leukemia (ALL) and have relapsed at least twice or no longer respond to standard treatments. A personalized cellular therapy, Kymriah is the first gene therapy to be approved for use in the U.S.
To produce Kymriah, T-cells (a type of immune cell) must first be harvested from the individual patient. They are then sent to a manufacturing center, where they are modified with a gene containing a chimeric antigen receptor (CAR) that targets the CD19 antigens expressed by ALL cancer cells. Once the modified T-cells are infused back into the patient, they seek out and attack the cancer cells. In a clinical trial, Kymriah produced an overall remission rate of 83% after three months.
Each dose is custom-manufactured for the individual patient, and is shipped in a single, frozen IV bag containing between 10mL and 50mL of Kymriah suspension. Frozen in liquid nitrogen, the product will be delivered directly to the facilities where it will be administered, and will not be distributed through pharmacies. At present, patients are expected to receive Kymriah as a one-time treatment.
Novartis has priced Kymriah at $475,000, and is exploring outcomes-based pricing models, in which full payment is only required when patients respond to treatment. Such an arrangement has already been reached with the Centers for Medicare and Medicaid Services (CMS) for patients covered under Medicaid. It is not yet known what pay-for-performance pricing agreements Novartis may reach with other payers.
ALL is an aggressive form of bone marrow and blood cancer. It is also the most common form of childhood cancer in the U.S. According to the National Cancer Institute, approximately 3,100 patients 20 years of age and younger are diagnosed with the disease each year. An estimated 15-20% of patients experience a relapse following initial treatment. At present, patients with ALL have few available treatment options.
Patients who are prescribed Kymriah require pretreatment with chemotherapy, and must be monitored for adverse effects. Kymriah carries a black box warning that its use has been associated with adverse neurological events, including delirium and encephalopathy, as well as cytokine release syndrome (CRS). Both CRS and neurological complications may be fatal. As a result, Kymriah must be used with a risk evaluation and mitigation strategy. Other potential side effects include acute kidney injury, hypotension, and increased risk of infection.
The FDA is currently reviewing a second CAR-T therapy, axicabtagene ciloleucel, developed by Kite. This therapy is intended for the treatment of patients with relapsed and/or refractory aggressive B-cell non-Hodgkin lymphoma (NHL) who are not candidates for stem cell transplants. Approval is anticipated by late November, 2017. Kite was purchased by Gilead in August of this year.
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