FDA approves first gene therapy in the United States – Pharmacy Today, American Pharmacists Association, pharmacist.com

FDA has approved the first gene therapy in the United States, tisagenlecleucel (KymriahNovartis), ushering in a new approach to treatment of cancer and other serious and life-threatening diseases, said the agency in a recent news release.

Tisagenlecleucel is the first autologous T-cell immunotherapy with genetically modified immune cells that target B-cell precursor acute lymphoblastic leukemia (ALL), the most common pediatric malignancy in children and young adults up to age 25 years. The product is indicated for patients who have treatment-resistant, relapsed, or refractory disease.

We consider this a major milestone in the development of cancer immunotherapies, said William Greene, PharmD, chief pharmaceutical officer at St. Jude Childrens Research Hospital, in a statement to pharmacist.com. It has the potential not only to improve outcomes, but also to reduce treatment-related complications for all cancer patients.

Approval of the product was based on a multicenter clinical trial of 63 pediatric and young adult patients with relapsed or refractory B-cell precursor ALL, whose overall remission rate within 3 months of treatment was 83%.

Each dose of tisagenlecleucel is a customized treatment created using an individual patients own T-cells. The cells are collected and sent to a manufacturing center, where they are genetically modified to include a new gene that contains a chimeric antigen receptor (CAR). The CAR directs the T-cells to target and kill leukemia cells that have a CD19 antigen on the surface. Once the cells are modified, they are infused back into the patient to kill the cancer cells.

The CD19-CAR was originally developed more than a decade ago at St. Jude by Dario Campana, MD, Greene said.

Adverse effects of tisagenlecleucel include serious infections, low blood pressure, acute kidney injury, fever, and decreased oxygen. The symptoms can appear within 1 to 22 days following infusion. The product was approved with a risk evaluation and mitigation strategy.

Tisagenlecleucel carries a boxed warning for severe, possibly life-threatening adverse effects such as neurological events and cytokine release syndrome (CRS), a systemic response to the activation and proliferation of CAR T-cells that causes high fever and flulike symptoms. FDA expanded the approval of tocilizumab (ActemraGenentech) to treat CRS and is requiring staff involved in prescribing, dispensing, or administering tisagenlecleucel to be trained to recognize and manage CRS and neurological events. Practitioners must have protocols in place to ensure that tisagenlecleucel is given to patients only after verifying that tocilizumab is available for immediate administration.

Optimal management [will require] careful planning for the provision of appropriate supportive care, Greene said. He also noted that approval of this therapy as a pharmaceutical presents interesting challenges to institutions in regard to handling, cost (budget implications), and reimbursement.

FDA is requiring Novartis to conduct a postmarketing observational study of patients treated with tisagenlecleucel.

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FDA approves first gene therapy in the United States - Pharmacy Today, American Pharmacists Association, pharmacist.com