US regulators have placed on hold studies of French drugmaker Cellectis’ CAR-T therapy following a patient fatality.
The move comes after the death of the first patient with blastic plasmacytoid dendritic cell neoplasm (BPDCN) to be treated with UCART123 in an early stage trial, following complications including cytokine release syndrome (CRS).
CRS, which is often referred to as an infusion reaction, is linked with the administration of many monoclonal antibodies. It is caused by the release of cytokines from cells targeted by the antibody as well as immune effector cells in the area, and can result in a range of symptoms including fever, nausea, chills, hypotension and tachycardia, which can be life-threatening in severe cases.
The patient reportedly experienced a grade 2 CRS on day five of the study as well as a grade 3 lung infection. Despite improvement after being treated with Roche's Actemra (tocilizumab) and antibiotics, the patient developed grade 5 CRS on day eight alongside grade 4 capillary leak syndrome - massive leakage of plasma and other blood components from blood vessels into neighbouring body cavities and muscles - and died on day nine.
As a result the US Food and Drug Administration has placed on hold all Phase I trials assessing the cell therapy in patients with BPDCN and those with acute myeloid leukaemia (AML).
Cellectis said it is now working closely with investigators and the FDA in order to resume the trials with an amended protocol including a lowered dosing of UCART123.
The group’s stock fell more than 25 percent in the aftermath of news.
Last week US regulators approved the first cell therapy - Novartis Kymriah - as a treatment for B-cell acute lymphoblastic leukaemia. But Kymriah differs from Cellectis’ cell therapy in that the treatment is based on patient's own t-cells, while UCART123 is derived from donors.