Kymriah First Gene Therapy Approved by the FDA, Indicated for Young Patients with B-Cell ALL and CD19

October 2017, Vol 7, No 10 - FDA News


On August 30, 2017, the FDA approved tisagenlecleucel (Kymriah; Novartis Pharmaceuticals), a genetically modified chimeric antigen receptor (CAR) T-cell immunotherapy, for the treatment of pediatric patients and young adults aged ≤25 years with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). Tisagenlecleucel is the first gene therapy ever to receive FDA approval, ushering in a new type of immunotherapy for patients with cancer. This is the first drug that uses the patient’s own T-cells, which are being genetically modified, to be targeted against leukemia cells that have CD19 antigens on their surface. The modified immune CAR T-cells are then infused back into the patient to fight the cancer 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,” said FDA Commissioner Scott Gottlieb, MD. “New technologies such as gene and cell therapies hold out the potential to transform medicine.”

Peter Marks, MD, PhD, Director of the FDA’s Center for Biologics Evaluation and Research, added, “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.”

The FDA used its priority review for this approval, and granted it a breakthrough therapy designation. The FDA approved tisagenlecleucel based on a multicenter clinical trial of 63 pediatric patients and young adults with relapsed or refractory B-cell ALL; the study showed an overall remission rate of 83% within 3 months of treatment.

Severe side effects reported with tisagenlecleucel include serious infections, hypotension, acute kidney injury, fever, and hypoxia. Most symptoms appeared within 22 days. Because the drug also kills normal B-cells (with CD19 antigen), tisagenlecleucel may increase the risk for infections for a long time. Furthermore, tisagenlecleucel carries a boxed warning about the risk for cytokine release syndrome, as well as neurologic side effects, which could be life-threatening. Tisagenlecleucel is therefore distributed only by authorized pharmacies through a Risk Evaluation and Mitigation Strategy program. In addition, the drug manufacturer is required to conduct a postmarketing observation study to confirm the safety of tisagenlecleucel.