RE:RE:CAR-T updateJanuary 25, 2024 - Engineered viruses are the dominant vectors in current gene therapy (CAR-T) clinical studies. A plethora of viral vectors including adenovirus (Ad), adenoassociated virus (AAV), and herpes simplex virus (HSV) have become subjects of concern to the FDA since the risk of the emergence of a new cancer - caused by genomic integration from these engineered viral vectors that are used to deliver the CAR-T cells - has become a matter of concern by the FDA. Three months after launching an investigation into the risk of patients developing secondary T-cell cancers after receiving a CAR-T drug, the FDA has shared more information on the cases it has seen so far.
As of the end of 2023, the FDA noticed 22 cases of T-cell cancers following treatment with a CAR-T product, and about a third of them remain under investigation. CAR insertion, which indicates a possible contribution from the CAR-T therapy, was detected in the malignant clone in each of the three cases for which genetic sequencing was performed.
Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research (CBER) and Nicole Verdun, M.D., who leads the office of therapeutic products at CBER, shared the latest information in an article published in the New England Journal of Medicine.
The dispatch offers the first official glimpse at the evidence under review at the FDA since the agency announced its CAR-T safety probe in November. But the officials did not share the level of seriousness for the 14 cases that have been adequately investigated.
Previously, the FDA has characterized the outcomes of the secondary cancers as “serious,” including cases of hospitalization and death.
The secondary cancer cases have been reported for five of the six commercial CAR-T products. The one that didn’t have a report linked to it appears to be Gilead Sciences’ Tecartus, according to a label update demand from the FDA.
https://www.fiercepharma.com/pharma/fdas-peter-marks-shares-more-info-car-t-secondary-cancer-probe-calls-new-drug-construct