CAR-T Therapy Trial Halted: Parkinsonism Raises Safety Concerns
Leiden, Thursday, 15 August 2024.
Galapagos paused its CAR-T therapy trial for multiple myeloma after a patient developed Parkinsonism symptoms. This setback echoes similar issues with other BCMA-directed CAR-T therapies, prompting enhanced safety measures and regulatory review.
Understanding CAR-T Therapy
CAR-T (chimeric antigen receptor T-cell) therapy is a groundbreaking advancement in the field of healthtech. It involves modifying a patient’s own immune cells to recognize and attack cancer cells. Specifically, for multiple myeloma, the therapy targets the B-cell maturation antigen (BCMA) present on the surface of myeloma cells. This personalized approach has shown promise in treating relapsed or refractory multiple myeloma, offering hope to patients with limited treatment options.
Benefits and Mechanism of CAR-T Therapy
The primary benefit of CAR-T therapy lies in its ability to provide targeted treatment. By engineering T-cells to attack specific cancer cells, it minimizes damage to healthy cells, which is a significant advantage over traditional chemotherapy. Additionally, this method has demonstrated high response rates in clinical trials, with some patients achieving complete remission. The therapy works by extracting T-cells from the patient’s blood, genetically modifying them in a laboratory to express the CAR that targets cancer-specific antigens, and reintroducing these engineered cells into the patient’s body.
Concerns Over Neurotoxicity
Despite its potential, CAR-T therapy is not without risks. A recent study highlighted concerns about neurotoxicity, particularly parkinsonism—a condition characterized by movement disorders, cognitive impairment, and personality changes. These symptoms were observed in patients undergoing CAR-T therapy for multiple myeloma. For instance, in a phase 3 trial for the FDA-approved CAR-T drug Carvykti, 8 out of 285 patients experienced parkinsonism, with five exhibiting severe symptoms following cytokine-release syndrome (CRS) events[1].
Galapagos’ Response to Safety Concerns
In response to these alarming findings, Galapagos, a Belgium-based biotechnology company, paused enrollment in its phase 1/2 clinical trial for the BCMA-directed CAR-T candidate GLPG5301. This decision came after a patient developed parkinsonism symptoms during the study. Galapagos filed a protocol amendment with the European Medicines Agency (EMA) to enhance patient monitoring and ensure safety. According to Dr. Jeevan Shetty, Head of Clinical Development Oncology at Galapagos, the company is committed to thoroughly investigating the adverse event and has implemented additional safety measures to mitigate risks[2].
Regulatory and Industry Implications
The implications of these findings extend beyond Galapagos. U.S. regulators have issued boxed warnings for CAR-T therapies, underscoring serious side effects, including parkinsonism and Guillain-Barré syndrome. While Bristol Myers Squibb’s CAR-T drug Abecma does not carry a boxed warning for parkinsonism, it has been reported as an adverse event. This highlights the need for rigorous safety protocols and continuous monitoring in clinical trials to safeguard patient health[3].
Future of CAR-T Therapy
Despite the challenges, the future of CAR-T therapy remains promising. Galapagos plans to resume its trial recruitment shortly, with data expected to be shared in 2025. The company remains focused on advancing its innovative treatments while ensuring patient safety. The ongoing research and development in CAR-T therapies are crucial for addressing unmet medical needs and improving outcomes for patients with severe hemato-oncological conditions. As the field evolves, enhanced safety measures and regulatory oversight will be essential to mitigate risks and realize the full potential of this transformative therapy[4].