The U.S. Food and Drug Administration approved Tecelra (afamitresgene autoleucel), a gene therapy indicated for the treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA antigen(s) A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive, and whose tumor expresses the MAGE-A4 antigen as determined by FDA authorized companion diagnostic devices.
Tecelra is also of the first FDA-approved T cell receptor (TCR) gene therapies. The product is an autologous T cell immunotherapy composed of a patient’s own T cells. T cells in Tecelra are modified to express a TCR that targets MAGE-A4, an antigen (substance that normally triggers your immune system) expressed by cancer cells in synovial sarcoma. The product is administered as a single intravenous dose.
Tecelra was approved using the Accelerated Approval pathway, under which the FDA may approve drugs for serious or life-threatening diseases or conditions where there is an unmet medical need and the drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients (improving how patients feel or function, or whether they survive longer). This pathway can allow earlier approval while the company conducts further trials to verify the predicted clinical benefit. A confirmatory trial is ongoing to verify Tecelra’s clinical benefit.
The safety and effectiveness of Tecelra was evaluated in a multicenter, open-label clinical trial including patients with inoperable and metastatic synovial sarcoma who had received prior systemic therapy and whose tumor expressed the MAGE-A4 tumor antigen. Effectiveness was evaluated based on overall response rate and the duration of response to treatment with Tecelra. Among the 44 patients in the trial who received Tecelra, the overall response rate was 43.2% and the median duration of response was six months.
The most common adverse reactions associated with Tecelra included nausea, vomiting, fatigue, infections, fever, constipation, dyspnea (shortness of breath), abdominal pain, non-cardiac chest pain, decreased appetite, tachycardia (abnormally fast heart rate), back pain, hypotension, diarrhea and edema (swelling due to buildup of fluid in body tissues).
Patients treated with Tecelra may experience cytokine release syndrome (CRS), which is a dangerous type of aggressive immune system response, including potentially life-threatening reactions. CRS was observed following administration of Tecelra during clinical trials. A Boxed Warning is included in the label containing information about this risk.
Patients may also exhibit Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS), an immune system-related syndrome that can occur following some immunotherapies, infections, secondary malignancies, or hypersensitivity reactions, and severe cytopenia (an abnormally low level of blood cells) for several weeks following lymphodepleting chemotherapy and Tecelra infusion. Patients receiving this product should be monitored for signs and symptoms of infection and are advised not to drive or engage in hazardous occupations or activities for at least four weeks after receiving Tecelra.
The FDA granted Tecelra Orphan Drug, Regenerative Medicine Advanced Therapy and Priority Review designations for this indication.
This application was reviewed using a coordinated, cross-agency approach, including CBER, the FDA’s Oncology Center of Excellence and the Center for Devices and Radiological Health.
The FDA granted the approval of Tecelra to Adaptimmune, LLC.
