| Drug Name |
TECELRA® (afamitresgene autoleucel) |
| Active Ingredient |
afamitresgene autoleucel |
| Date of Approval |
August 1, 2024 |
| Manufacturer |
Adaptimmune Therapeutics plc |
| Approval Pathways and Indications |
Approval Pathway: Accelerated Approval
Indication: TECELRA® is approved for adults with unresectable or metastatic synovial sarcoma who are HLA-A02:01P, -A02:02P, -A02:03P, or -A02:06P positive, have undergone prior chemotherapy, and have tumors expressing MAGE-A4, as confirmed by FDA-approved diagnostics. |
| Therapeutic Class |
Immunotherapy |
| Formulation |
Suspension for Intravenous Infusion |
| MoA |
TECELRA® is a personalized T cell therapy using genetically modified CD4 and CD8 T cells. These cells are engineered to express an enhanced TCR that targets the MAGE-A4 peptide, presented by HLA-A*02 on synovial sarcoma cells. TECELRA® activates T cells to proliferate, secrete cytokines, and kill cancer cells that express MAGE-A4. |
| Dosing and Administration |
TECELRA® Administration Instructions:
Formulation: Cell suspension for intravenous infusion in infusion bags containing 2.68 x 10^9 to 10 x 10^9 MAGE-A4 TCR positive T cells.
Dosage: 2.68 x 10^9 to 10 x 10^9 MAGE-A4 TCR positive T cells.
Preparation:
Administer a lymphodepleting regimen with cyclophosphamide and fludarabine.
Premedicate with acetaminophen and an H1-antihistamine.
Administration:
Infuse within one hour of thawing.
Avoid using a leukodepletion filter or prophylactic systemic corticosteroids. |
| Administered by self or by HCP |
Administered by HCP |
| Place in Therapy |
TECELRA® is the first engineered TCR cell therapy approved in the U.S. for synovial sarcoma, offering a new treatment option after more than a decade. Unlike CAR-T therapies, TECELRA® targets the intracellular protein MAGE-A4, potentially making it more effective against solid tumors.
While TECELRA® has shown promise, its long-term efficacy in extending patient survival is not yet proven. Early analysis indicates a two-year survival probability of about 70% for responding patients. Continued data collection is necessary to fully understand its safety and effectiveness, especially as Adaptimmune expands treatment centers.
TECELRA® has a black box warning for cytokine release syndrome and can cause serious side effects, including neurotoxicity, severe cytopenia, infections, secondary malignancies, and hypersensitivity reactions. It is contraindicated in adults who are heterozygous or homozygous for HLA-A*02:05P. |
| Expected Market Launch Date |
Fourth quarter of 2024 |
| New Molecular Entity (NME) or Existing Formulation |
Existing Formulation |
| Expected Cost |
$727,000 per dose |
| Product Discontinuation |
N/A |
| Clinical Trials |
Efficacy was evaluated in SPEARHEAD-1, Cohort 1, a multicenter, single-arm, open-label clinical trial that enrolled HLA-A*02:01-03 and 06 allele positive patients with inoperable or metastatic synovial sarcoma who had received prior systemic therapy with either doxorubicin and/or ifosfamide and whose tumor expressed the MAGE-A4 tumor antigen. Patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide.
Fifty-two patients with synovial sarcoma were enrolled and underwent leukapheresis, eight of whom did not receive afamitresgene autoleucel due to death (n=3), loss of eligibility prior to lymphodepleting chemotherapy (n=3), withdrawal by patient (n=1), and investigator decision (n=1). Forty-five patients received lymphodepletion and one patient withdrew consent before treatment, for a total of 44 patients who received a single infusion of afamitresgene autoleucel.
The main efficacy outcome measure was overall response rate (ORR) according to RECIST v1.1 evaluated by independent review, supported by duration of response (DOR). ORR was 43.2% (95% Confidence Interval [CI]: 28.4, 59.0). The median time to response was 4.9 weeks (95% CI: 4.4 weeks, 8 weeks). The median DOR was 6 months (95% CI: 4.6, not reached). Among patients who were responsive to the treatment, 45.6% and 39.0% had a duration of response greater than or equal to 6 months and 12 months, respectively. |
| Sources |
FDA approves first gene therapy to treat adults with metastatic synovial sarcoma. U.S. Food and Drug Administration. Published July 31, 2024. Accessed August 5, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treat-adults-metastatic-synovial-sarcoma
FDA grants accelerated approval to Tecelra (afamitresgene autoleucel) cell therapy for synovial sarcoma. Drugs.com. Published August 1, 2024. Accessed August 5, 2024. https://www.drugs.com/newdrugs/fda-grants-accelerated-approval-tecelra-afamitresgene-autoleucel-cell-therapy-synovial-sarcoma-6339.html
FDA grants accelerated approval to afamitresgene autoleucel for unresectable or metastatic synovial sarcoma. U.S. Food and Drug Administration. Published July 31, 2024. Accessed August 5, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-afamitresgene-autoleucel-unresectable-or-metastatic-synovial-sarcoma
FDA briefing document: Tecelra (afamitresgene autoleucel). U.S. Food and Drug Administration. Published July 2024. Accessed August 5, 2024. https://www.fda.gov/media/180565/download
Adaptimmune receives U.S. FDA accelerated approval of afamitresgene autoleucel (afami-cel) as first-genetically-engineered T-cell therapy for synovial sarcoma. Adaptimmune. Published July 31, 2024. Accessed August 5, 2024. https://www.adaptimmune.com/investors-and-media/news-center/press-releases/detail/271/adaptimmune-receives-u-s-fda-accelerated-approval-of
Adaptimmune's Tecelra wins FDA approval for synovial sarcoma in first for TCR cell therapy. BioPharma Dive. Published July 31, 2024. Accessed August 5, 2024. https://www.biopharmadive.com/news/adaptimmune-tecelra-fda-approval-synovial-sarcoma-tcr-cell-therapy/723156/
Tecelra. Drugs.com. Accessed August 5, 2024. https://www.drugs.com/tecelra.html
Sunny M. US FDA approves Adaptimmune's therapy for rare type of cancer. Reuters. August 2, 2024. Available at: https://www.reuters.com/business/healthcare-pharmaceuticals/us-fda-approves-adaptimmunes-gene-therapy-rare-cancer-2024-08-02/. Accessed August 5, 2024. |