The US FDA has just announced the historic news that the first gene therapy CAR-T cell drug has been approved for marketing. The approval of such therapeutic drugs has given cancer and other serious and life-threatening diseases a new legal treatment option.

The first CAR-T drug approved by the FDA

Indications: Acute lymphoblastic leukemia (ALL) in children and young adults

Drug brand name: Kymriah ( tisagenlecleucel )

“We are entering a new era of medical innovation,” said FDA Commissioner Scott Gottlieb, M.D. “New technologies, such as gene and cell therapies, have the potential to advance transformational medicine by reprogramming a patient’s own cells to attack deadly cancer cells and create a new inflection point in our ability to treat and cure many intractable diseases. The FDA is committed to helping expedite the development and review of breakthrough therapies that have the potential to save lives.”

Kymriah, a cell-engineered gene therapy, is approved in the U.S. for the treatment of patients up to 25 years old with refractory or relapsed acute lymphoblastic leukemia (ALL).

Kymriah is a genetically modified autologous T-cell immunotherapy. Each dose of Kymriah is a customized treatment produced using an individual patient's own T cells (a type of white blood cell called a lymphocyte). The patient's T cells are collected and sent to a manufacturing center, where they are genetically modified (new gene expression of a chimeric antigen receptor, or CAR), which directs the T cells to target and kill cancer cells that have a specific antigen on their surface (CD19). Once the cells are modified, they can kill cancer cells when they are infused into the patient.

ALL is a cancer of the bone marrow and blood in which the body's lymphocytes become abnormal. The disease progresses quickly and is the most common childhood cancer in the United States. The National Cancer Institute estimates that approximately 3,100 patients younger than 20 years old are diagnosed with ALL each year. ALL can be of T-cell or B-cell origin, with B-cells being the most common. Kymriah is approved for pediatric and young adult patients with B-cell ALL, and is indicated for patients with relapsed or refractory ALL, which accounts for 15-20% of patients.

“Kymriah is the first cell-based gene therapy that addresses an important need for children and young adults with this serious disease,” said Peter Marks, M.D., director of the FDA’s Center for Biologics Evaluation. “These patients have very limited options, and Kymriah not only provides a new treatment option for these patients, but more importantly, one that has shown promising response rates and improved survival in clinical trials.”

The safety and efficacy of Kymriah were demonstrated in a multicenter clinical trial of pediatric and young adult patients with relapsed or refractory B-cell ALL. The overall response rate within three months of treatment was 83%.

Treatment with Kymriah has potentially serious side effects. Risk warnings may be issued, such as cytokine release syndrome (CRS), which can cause high fever and flu-like symptoms, and severe damage to the nervous system due to the rapid proliferation of CAR T cells. Both CRS and neurological events can be life-threatening.

Other serious side effects of Kymriah include severe infection, low blood pressure (hypotension), acute kidney injury, fever, and decreased oxygen (hypoxia). Most symptoms appear between 1 and 22 days after the Kymriah infusion. Because the CD19 antigen is also present on normal B cells, and Kymriah also destroys normal B cells that produce antibodies, there is an increased risk of prolonged infection.

At the same time, the FDA also expanded the approval of Actemra (tocilizumab) today to treat severe or life-threatening CRS side effects induced by CAR-T cells in patients aged 2 years and older. In a clinical trial of patients treated with CAR-T cells, 69% of patients had complete resolution of CRS within two weeks after one or two doses of Actemra.