Historic FDA Approval Makes First Gene Therapy Available in U.S.


The first gene therapy in the United States has been approved by the Food and Drug Administration (FDA). Kymriah (tisagenlecleucel; Novartis), the first chimeric antigen receptor T cell (CAR-T) therapy, is indicated to treat patients up to 25 years old with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.

Kymriah is a customized, one-time treatment created using the patient's own T-cells. The T-cells are collected then sent to a manufacturing center where they are genetically modified before being infused back into the patient. The modification provides a chimeric antigen receptor (CAR) which directs the T-cells to target and kill leukemia cells that have a specific antigen (CD19) on the surface.

“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 and create an inflection point in our ability to treat and even cure many intractable illnesses.” 

A multicenter trial of 63 pediatric and young adult patients with relapsed or refractory B-cell precursor ALL demonstrated the safety and efficacy of Kymriah. Results showed that the treatment produced an overall remission of 83% within 3 months. 

Kymriah comes with a boxed warning for neurological events and cytokine release syndrome (CRS), which can both be life-threatening. Because of this, the treatment has been approved with a risk evaluation and mitigation strategy (REMS), requiring hospitals and clinics to be specially certified. In addition, clinicians involved in the prescribing, dispensing, and administering of the therapy will need training to recognize these side effects.  

In response to the possibility of CRS development, the FDA has also expanded the approval of tocilizumab (Actemra; Genentech) to treat CAR-T cell-induced severe or life-threatening CRS in patients 2 years of age and older. According to the REMS, healthcare settings where Kymriah will be administered will need to verify that tocilizumab is available for immediate administration.

Other severe side effects of Kymriah include serious infections, hypotension, acute kidney injury, fever, and hypoxia; most of these symptoms have appeared within 1–22 days after the infusion. Patients may be at increased risk for infections for a prolonged period of time after infusion as the treatment may also destroy normal B cells. 

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“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,” said Peter Marks, MD, PhD, director of the FDA.

The creation of Kymriah (Formerly known as ‘CTL019') has been part of a collaboration started in 2012 between Novartis and the University of Pennsylvania.

“Through our collaboration with Novartis, we are creating the next wave of immunocellular cancer treatments, and are eager to progress CAR-T therapy in a host of hematologic and other cancer types,” said Carl June, MD, Professor of Immunotherapy, Director of the Center for Cellular Immunotherapies in Penn's Perelman School of Medicine.

For more information visit FDA.gov.