FDA approves first gene therapy – tisagenlecleucel for ALL

The U.S. Food and Drug Administration has approved tisagenlecleucel (Kymriah), a first-of-its-kind chimeric antigen receptor T-cell (CAR T) therapy, for the treatment of children and young adults up to age 25 years with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.

Tisagenlecleucel will carry a boxed warning regarding the CRS risk. Additionally, due to the CRS risk and risk of neurological events, the approval requires a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use, according to an FDA press release .

Special certification will be required for hospitals and associated clinics that dispense tisagenlecleucel. As part of certification, staff will be trained in the prescribing, dispensing, or administering of the therapy, and to recognize and manage CRS and neurological events.

Novartis, the maker of tisagenlecleucel, will be required to conduct postmarketing observational study.

^{Courtesy Novartis}

CAR-T cell therapies are manufactured for each individual patient, extracting a patient’s T cells to reprogram them outside of the body to recognize and fight specific cells, including cancer cells.

Indeed, FDA commissioner Scott Gottlieb, MD, said the approval marks the entry to a “new frontier in medical innovation.”

“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,” he said in the press statement.

Tisagenlecleucel is a genetically modified autologous T-cell immunotherapy involving customized treatment created using a patient’s own T cells. The T cells are genetically modified to include a chimeric antigen receptor that directs the T cells to target and kill leukemia cells with CD19 surface antigen, and are then infused back into the patient.

In a phase 2 clinical trial, the overall remission rate with tisagenlecleucel therapy was 83% in 63 children and young adults with relapsed/refractory B-cell precursor ALL for whom at least two prior lines of therapy had failed; the therapy was granted Fast Track, Priority Review, and Breakthrough Therapy designations.

“Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for children and young adults with this serious disease,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research said in the press statement.

“Not only does Kymriah provide these patients with a new treatment option where very limited options existed, but a treatment option that shows promising remission and survival rates in clinical trials.”