FDA Approves Kymriah
First Gene Therapy, New Kind of Cancer Treatment
In a press release the Food and Drug Administration (FDA) has announced its approval of a chimeric antigen receptor (CAR) T-cell gene therapy for treatment of childhood and adolescent B-cell acute lymphoblastic leukemia (ALL) for patients up to 25. ALL affects blood and bone marrow cells and is the most frequent childhood cancer. According to the National Cancer Institute, there are 3,100 new cases per year.
The new treatment, Kymriah, pioneered by Novartis Pharmaceuticals Corporation, is a genetically altered autologous T-cell, which means that it is tailored for a specific patient and created from the patient’s own lymphocytes. The patient’s lymphocytes (T-cells) are altered in a laboratory and given a new gene that includes the protein CAR, which influences T-cells to attack leukemia cells containing the antigen CD19. The altered cells are then re-injected into the patient.
FDA Commissioner Scott Gottlieb, M.D., said, “We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer. 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. At the FDA, we’re committed to helping expedite the development and review of groundbreaking treatments that have the potential to be life-saving.”
Kymriah is meant for the 15 to 20 percent of cases that fail to respond to existing treatments, or where the cancer has returned. In a clinical trial of 63 pediatic ALL patients, the remission rate in less than 3 months was more than 83 percent.
Peter Marks, M.D., Ph.D., director of the FDA Center for Biologics Evaluation and Research (CBER), said, “Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for children and young adults with this serious disease. 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.”
Serious side effects are possible with Kymriah. Cytokine release syndrome (CRS), an autoimmune reaction to the presence of CAR T-cells, causes high fever and neurological problems that are dangerous. Because the CD19 antigen is also found on normal B-cells, Kymriah will attack them, leading to higher risk of infections and fevers as these noncancerous immune system cells are destroyed. There are increased risks of hypotension, hypoxia and kidney damage as well.
Because the CRS especially is considered so dangerous, the FDA has moved quickly to approve the drug Actemra, made by Genentech, Inc., to treat it. Actemra has demonstrated cure in 69 percent of CRS patients within a brief period. Facilities that administer Kymriah must be FDA-certified, train their staffs to spot and treat CRS and have Actemra available for quick use. Patient education in CRS symptoms is also required.
The FDA is requiring Novartis Pharmaceuticals to do a continuing observational study of Kymriah as it goes into use.