FDA approves world’s first pioneering gene therapy for cancer

The U.S.Food and Drug Administration in its landmark and historic action today approved the world’s first gene therapy, Novartis' Kymriah (tisagenlecleucel) for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia (ALL).

This opens a new frontier in treatment of cancer and other serious and life-threatening diseases.

FDA Commissioner Scott Gottlieb, M.D. said in a press release,” “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.”

The highly personalized therapy is called chimeric antigen receptor (CAR) therapy, in which patients’ T cells are removed from the body and are transported to a Novartis facility in New Jersey. Here, viruses are used to insert gene in the cells. The gene will code for a protein called chimeric antigen receptor, which modify the T-cells to destroy cancer cells.

The cells are than reinfused in the patient.FDA approval came in the wake of successful results of a  pivotal open-label, multicenter, single-arm Phase II ELIANA trial, the first pediatric global CAR-T cell therapy registration trial examining patients in 25 centers in the US, EU, Canada, Australia and Japan. In a trial of 63 patients treated with Kymriah, 83% were in remission after three months, and 64% were still in remission after a year.

Kymriah is approved for use in pediatric and young adult patients (<25 years of age)  with B-cell ALL, whose treatment has not responded to any other therapeutic option or their cancer has relapsed.

The potential side effects with Kymriah are cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR T-cells causing high fever and flu-like symptoms, and for neurological events. These are life threatening. Other side effects include serious infections, low blood pressure (hypotension), acute kidney injury, fever, and decreased oxygen (hypoxia). Most symptoms appear within one to 22 days following infusion of Kymriah. Since the CD19 antigen is also present on normal B-cells, and Kymriah will also destroy those normal B cells that produce antibodies, there may be an increased risk of infections for a prolonged period of time.

Administration of Kymriah requires that it is dispensed in specially certified hospitals with staff that is trained to handle life threatening emergencies like cytokine release syndrome (CRS).

The FDA today also expanded the approval of Actemra (tocilizumab) to treat CAR T-cell-induced severe or life-threatening CRS in patients 2 years of age or older.

FDA also requires that Novartis conducts a post-marketing observational study involving patients treated with Kymriah.

"I think this is the most exciting thing I've seen in my lifetime," said Dr. Tim Cripe, an oncologist who was part of the FDA advisory committee panel that voted in July to recommend the drug's approval.

"At Novartis, we have a long history of being at the forefront of transformative cancer treatment," said Joseph Jimenez, CEO of Novartis. "Five years ago, we began collaborating with the University of Pennsylvania and invested in further developing and bringing what we believed would be a paradigm-changing immunocellular therapy to cancer patients in dire need. With the approval of Kymriah, we are once again delivering on our commitment to change the course of cancer care."

FDA Press Release

Novartis Press Release