Cell therapies first reached patients as treatments for blood cancers. Adaptimmune Therapeutics’ work in this therapeutic modality has culminated in an FDA nod in synovial sarcoma, a regulatory decision that makes the new product the first engineered cell therapy approved for treating a solid tumor.
Known in development as afamitresgene autoleucel, or afami-cel, the new Adaptimmune product will be marketed under the brand name Tecelra.
“Adaptimmune was founded on the conviction that cell therapy would revolutionize the treatment of cancer,” CEO Adrian Rawcliffe said, speaking during a Friday conference call. “This has been demonstrated in the hematological cancer space and Tecelra’s approval is a significant milestone in our journey to expand cell therapy to solid tumors.”
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Like CAR T-therapy, the first generation of cell therapy, Tecelra is made by harvesting a patient’s T cells and engineering them in a lab. While CAR T-drugs are engineered to recognize and bind to a target on a tumor’s surface, Oxford, U.K.-based Adaptimmune engineers therapies with T cell receptors (TCRs) that can recognize targets on the inside of a cancer cell. This capability makes TCR cell therapies better suited for addressing the solid tumors that have eluded CAR T-therapies.
Tecelra is designed to target MAGE-A4, an antigen overexpressed in many solid tumors, including synovial sarcoma. This type of cancer develops in soft tissues of the body, such as muscles and ligaments. It’s rare, affecting about 1,000 people in the U.S. annually, often males in their 30s or younger, according to the FDA. The first line of treatment is surgery to remove the tumors. Radiotherapy and chemotherapy are used for larger tumors or tumors that have spread.
FDA approval of Tecelra is based on the results of an open-label Phase 2 clinical trial that enrolled 44 patients with advanced synovial sarcoma that expressed MAGE-A4. Results showed treatment with Tecelra resulted in a 43% overall response rate; the complete response rate was 4.5%. The median duration of response to the one-time treatment was six months. Of those who responded to Tecelra, 39% had a response lasting 12 months or longer. Results were published in April in the journal The Lancet.
The most common adverse effects reported in the study included nausea, vomiting, fatigue, and infections. Tecelra’s label carries a black box warning for cytokine release syndrome, an excessive immune response. The label also warns of the risk of neurotoxicity. Both complications are known risks of cell therapies and are flagged on the labels of other cell therapy products.
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All Tecelra doses for clinical trials were manufactured internally by Adaptimmune. Rawcliffe said the company will make commercial doses of the therapy at its Philadelphia site and the first commercial sale is expected in the fourth quarter of this year. Before patients can begin treatment, they must first be tested for the MAGE-A4 antigen. The FDA has approved an Agilent Technologies companion diagnostic to identify synovial sarcoma patients eligible for Tecelera.
Tecelra is technically not the first FDA-approved cell therapy for a solid tumor. That honor belongs to Iovance’s Amtagvi, a therapy made from tumor-infiltrating lymphocytes (TILs) that won its FDA approval in February. Amtagvi’s manufacturing process involves isolating TILs from a sample of a patient’s tumor and multiplying those cells in a lab. Because TILs come from the patient’s tumor, they already recognize it and thus do not need the engineering step that is a key part of manufacturing CAR T-and TCR-therapies.
Amtagvi’s $515,000 price topped the price range of CAR T-therapies. Now Tecelra is topping Amtagvi. Adaptimmune set a $727,000 list price for Tecelra, its first commercialized product. Chief Commercial Officer Cintia Piccina said the price reflects the clinical value the cell therapy brings to patients who have a rare type of tumor with high unmet need. The regulatory decision is an accelerated approval based on the Phase 2 data. A confirmatory study is ongoing. Adaptimmune is also running another clinical trial that could support expanding Tecelra’s use to pediatric patients. The company projects Tecelra’s annual sales could reach a peak of $400 million.
Adaptimmune plans to expand its reach in sarcomas. Another program in the pipeline could address synovial sarcoma as well as myxoid round cell liposarcoma (MRCLS), a soft tissue cancer that also has limited treatment options. This cell therapy, lete-cel, is engineered to go after a target called IGNYTE-ESO. Initially partnered with GSK, the pharmaceutical giant terminated the alliance in 2022 and returned all rights to Adaptimmune. Rawcliffe said the company expects to begin a rolling biologics license application for lete-cel next year.
A separate cell therapy alliance with Roche is ongoing. In May, Adaptimmune began a partnership with Galapagos. The Belgian company licensed certain rights to uza-cel, a MAGE-A4-targeting TCR cell therapy. Adaptimmune advanced uza-cel to late-stage clinical testing in ovarian cancer, and the company retains rights in this indication. Galapagos paid Adaptimmune $70 million cash up front for rights to develop uza-cel in head and neck cancer as well as other solid tumors. R&D funding and option exercise fees could add up to $30 million more to the deal. As of the end of the first quarter of this year, Adaptimmune reported a cash position of about $144 million, which it estimated would support the company into late 2025.
Public domain image by the National Cancer Institute