FDA Grants Approval for First-Ever Gene Therapy for Adults Battling Metastatic Synovial Sarcoma
Synovial sarcoma is a relatively uncommon type of cancer that affects approximately 1000 adults in the United States annually, with a higher incidence among men in their 30s or younger
On August 2, 2024, the FDA approved Tecelra (afamitresgene autoleucel), a groundbreaking gene therapy developed by Adaptimmune. This therapy is specifically designed to treat synovial sarcoma, a rare form of cancer that is difficult to remove surgically or has spread to other parts of the body. It is intended for use in adults who have already undergone chemotherapy, test positive for certain human leukocyte antigens (HLA), and have tumors that may express melanoma-associated antigen (MAGE)-A4, as determined by a diagnostic device.
The FDA has announced that Tecelra is the first T-cell receptor (TCR) gene therapy to be approved. This autologous immunotherapy utilizes a patient's own T cells, which are genetically modified to express a TCR that specifically targets MAGE-A4 (1). The antigen is typically found in synovial sarcoma cancer cells and can activate the immune system. Tecelra patients may also test positive for other antigens such as HLA A02:01P, -A02:02P, -A02:03P, and -A02:06P.
Approximately 1000 individuals in the United States are diagnosed with synovial sarcoma each year. This type of cancer primarily affects adult males under the age of 40. It is characterized by the development of malignant cells that form tumors in soft tissue, commonly in the extremities. However, it can also occur in other areas of the body, and the cancerous cells have the potential to spread throughout the body (1). The tumor is typically treated through surgical removal, and additional treatment options such as radiotherapy and chemotherapy may be considered in cases where the tumor is large, has recurred, or has spread to other areas.
According to Nicole Verdun, MD, director of the Office of Therapeutic Products in FDA's Center for Biologics Evaluation and Research (CBER), adults with metastatic synovial sarcoma, a life-threatening form of cancer, frequently encounter restricted treatment choices and the potential for cancer spread or recurrence. Today's approval is a major achievement in the advancement of a groundbreaking treatment that offers safety and effectiveness for patients suffering from this rare yet life-threatening condition.
Tecelra was able to gain approval through the FDA's Accelerated Approval pathway, allowing Adaptimmune to continue conducting additional trials to confirm the therapy's expected benefits. Currently, there is an ongoing confirmatory trial. Accelerated Approval enables the FDA to advance specific drugs for the treatment of severe or life-threatening conditions with unmet medical needs. These drugs have shown positive effects on surrogate endpoints. According to the FDA, Tecelra showed promising results in a clinical trial involving multiple centers. Among 44 patients, it achieved a response rate of 43.2%, with a median duration of response lasting six months.
"Cancers like synovial sarcoma can be extremely dangerous and have a severe impact on individuals, particularly when standard treatments are not effective in stopping tumor growth and progression," stated Peter Marks, MD, PhD, the director of CBER. "The FDA's approval of this cutting-edge immunotherapy technology is a significant breakthrough for patients in need. It showcases the FDA's commitment to advancing effective cancer treatments."
Source: FDA
