The FDA has been actively involved in the cell and gene therapy space, with several key developments in August 2024. These include the approval of a novel T-cell therapy for synovial sarcoma, modifications to CAR-T risk management strategies, the lifting of a clinical hold on a gene therapy trial, and clearance for a pivotal CAR-T trial. These actions highlight the agency's commitment to advancing treatments for rare and challenging diseases.
First TCR T-Cell Therapy Approved for Solid Tumor
Adaptimmune Therapeutics' afamitresgene autoleucel (afami-cel), marketed as Tecelra, received accelerated approval for the treatment of adults with unresectable or metastatic synovial sarcoma (SS) who have received prior chemotherapy. This T-cell receptor (TCR) T-cell therapy targets the MAGE-A4 antigen and is the first engineered T-cell therapy approved for a solid tumor indication.
"Potentially life-threatening cancers such as synovial sarcoma continue to have a devastating impact on individuals, especially those for whom standard treatments have limited efficacy due to tumor growth and progression," said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research (CBER). He added that this approval "provides a critical new option for a patient population in need and demonstrates the FDA’s dedication to the advancement of beneficial cancer treatments."
Tecelra represents a significant advancement in the treatment of synovial sarcoma, offering a novel approach that utilizes the patient's own immune cells to target cancer cells. Sandra D’Angelo, MD, Sarcoma Medical Oncologist and Cell Therapist, Memorial Sloan Kettering Cancer Center, noted that the therapy "uses each patient’s own immune cells to recognize and attack their cancer cells in a one-time infusion treatment" and "is significantly different than the current standards of care for advanced synovial sarcoma."
Streamlining CAR-T Risk Management
The FDA has modified its Risk Evaluation and Mitigation Strategies (REMS) for autologous CAR-T immunotherapies to reduce the burden on healthcare systems. The modifications remove the requirements for educational and training materials regarding the risks of cytokine release syndrome (CRS) and neurological toxicities for approved CAR-T therapies, including Abecma, Breyanzi, Carvykti, Kymriah, Tecartus, and Yescarta. The FDA stated that information about these risks is adequately conveyed on current product labeling and boxed warnings. The requirement to report adverse events suggestive of CRS or neurological toxicities to the REMS has also been removed.
Clinical Hold Lifted for Fabry Disease Gene Therapy
A clinical hold on 4D Molecular Therapeutics' (4DMT) phase 1/2 INGLAXA clinical trial for 4D-310, a gene therapy for Fabry disease, has been lifted. The trial will resume enrollment before the end of 2024. The hold was initially placed due to instances of treatment-related serious adverse events of atypical hemolytic uremic syndrome. 4D-310 is an adeno-associated virus (AAV) vector-based gene therapy.
CAR-T Therapy for Nasopharyngeal Carcinoma Advances to Pivotal Trial
Biosyngen’s CAR-T therapy BRG01 has been cleared by the FDA for a pivotal phase 2 clinical trial in patients with Epstein-Barr virus (EBV)-positive relapsed/metastatic nasopharyngeal carcinoma. This follows clearance from China's National Medical Products Administration (NMPA) for a similar trial. BRG01 is the first cell therapy to move into a phase 2 clinical trial for this indication in both the US and China.
"The approval of the phase 2 clinical trial for BRG01 is a testament to the robust preclinical data and strong early clinical results observed with this innovative therapy," said Zhang Li, MD, MSc, the director of the Phase I Ward at the Sun Yat-Sen University Cancer Center and principal investigator for the BRG01 clinical trial. "BRG01 has the potential to be a first-in-class T-cell therapy for EBV-positive tumors, and we are confident in its ability to deliver meaningful clinical benefits to patients with this difficult-to-treat malignancy."
