The first chimeric antigen receptor T-cell therapy, tisagenlecleucel, received FDA approval for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia who haven't responded to standard therapy or who have relapsed at least twice.

Calling it “a historic action,” the FDA approved the first chimeric antigen receptor (CAR) T-cell therapy—tisagenlecleucel (Kymriah, CTL019; Novartis)—on August 30, “ushering in a new approach to the treatment of cancer and other serious and life-threatening diseases.”

Tisagenlecleucel was approved for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) who haven't responded to standard therapy or who have relapsed at least twice. Treatment involves genetically modifying a patient's own T cells to express CARs that target CD19 on the surface of the cancer cells.

The approval of tisagenlecleucel was not unexpected. In July, the FDA's 10-member Oncologic Drugs Advisory Committee unanimously recommended that the agency greenlight the therapy, based on an overall remission rate of 83% in a clinical trial involving 63 children and young adults.

The downside to the therapy is that patients who receive it are at risk for serious and potentially life-threatening side effects. Notable among them is cytokine release syndrome (CRS), a systemic response to the activation and proliferation of CAR T cells, which can provoke high fever and severe flu-like symptoms. Thus, tisagenlecleucel carries a boxed warning about CRS, as well as neurologic events. In addition, the FDA expanded the approval of the immunomodulatory drug tocilizumab (Actemra; Genentech), which blocks IL6. Normally prescribed to treat rheumatoid arthritis, tocilizumab completely resolved CRS within 2 weeks in 69% of patients in clinical trials.

Novartis will charge $475,000 for the one-time treatment. However, the company said that it wants to “deliver value-based care and ensure access” to the treatment for patients with ALL who qualify to receive it. To that end, Novartis announced a groundbreaking collaboration with the Centers for Medicare and Medicaid Services (CMS): The agency will be required to pay for tisagenlecleucel only if patients participating in those programs respond to the therapy within a month of treatment.

Such an arrangement may not be the first. “We look forward to continuing to work with CMS to potentially expand this approach to other products and disease states,” said Novartis CEO Joseph Jimenez. –Suzanne Rose