Authors: Francis Davies, Future Science Group
The US FDA has announced the availability of the first gene therapy in the USA. The novel gene therapy – tisagenlecleucel (Kymriah) – is intended for patients with B-cell precursor acute lymphoblastic leukemia (ALL) that has proved unresponsive to treatment, or has returned after initial treatments. The cell-based treatment will be restricted to patients of up to 25 years of age, with ALL that is refractory or post-first-stage relapse. This is estimated to occur in 15–20% of patients.
Kymriah is a genetically-modified, autologous T-cell immunotherapy. Each dose is customized by using the patient’s own T-cells, which are collected and modified at a manufacturing center and then infused back into the patient. The cells contain a gene containing a chimeric antigen receptor that directs T-cells to combat leukemia cells with the CD19 antigen on their surface.
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A multicenter clinical trial demonstrated the efficacy of Kymriah, demonstrating that of 63 pediatric and young adult patients with relapsed or refractory B-Cell precursor ALL, the overall remission rate stood at 83% within 3 months. However, Kymriah does carry the potential to induce severe side effects. The therapy’s warning list includes cytokine release syndrome and neurological events, both of which can be life-threatening. Most symptoms appear within 22 days of infusion. Kymriah will also destroy normal B-cells, due to the presence of CD19, resulting in a prolonged increase in the risk of infection.
Because of these risks, the FDA will require, amongst a number of safeguards, that all hospitals and associated clinics be specifically certified and all staff prescribing, dispensing or administering Kymriah, be trained in recognizing and treating cytokine release syndrome and neurological events. Patients will also be informed of the symptoms. Novartis will be conducting a post-marketing observational study involving patients treated with Kymriah.
Scott Gottlieb (FDA) commented: “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.”