UPDATE: The FDA has lifted both clinical holds provided that Cellectis decreases the dose of both UCART123 and the lymphodepletion regimen, the next three patients will be under the age of 65, and that a month passes between enrollments. The FDA also asked for further information to be recorded before patients began treatment, including uncontrolled infection after lymphodepletion, which pauses the immune system. The company is trading up at 8% after hours on Nasdaq.
Originally Published 05/09/2017
The FDA has instructed Cellectis to hold two ongoing CAR-T Phase I trials after a patient’s death that could be attributed to the side effects.
Less than a week since the first CAR-T therapy was approved by the FDA, the US regulatory agency has put two CAR-T trials on hold following a patient’s death. The patient, 78 and suffering from relapsed blastic plasmacytoid dendritic cell neoplasm (BPDCN), died 9 days after the administration of Cellectis’ UCART123 after experimenting severe cytokine release syndrome (CRS), a complication that is commonly associated with CAR-T therapies.
The FDA has called for a hold on two studies. First, the trial in BPDCN in which the deceased patient had been the first to be treated; and second, a study in acute myeloid leukemia (AML) in which the first patient, though resolved after 12 days, also suffered from severe CRS symptoms. Cellectis is now working on modifying the protocol and lowering the dosage to resume the trials.
The announcement has hit Cellectis hard, since UCART123 is its lead proprietary program and the first off-the-shelf CAR-T to enter clinical trials. The company’s shares on the Paris Stock Exchange were down by 29% when it opened this morning, while the effects on the Nasdaq shares will be seen when it opens in a few hours.
Deaths induced by side effects are sadly not a new thing in CAR-T trials. US biotech Juno Therapeutics had to terminate a CAR-T trial in March after five patients died from cerebral edema. The trial had been on hold after the first three deaths and resumed with a protocol modification, but permanently halted after two more patients died.
Kite Pharma, now waiting to receive approval for its CAR-T cell therapy KTE-C19, has also reported two deaths linked to the therapy. Novartis’ Kymriah, the first to be approved, is the only one with no deaths reported, though 49% of patients in its pivotal trial suffered from strong CRS.
It remains to be seen how the therapy behaves in the real world now that the first treatment is out there, but side effects are certainly one of the main concerns regarding CAR-T and other immunotherapies. Research on the long-term effects of these treatments seems to be lagging behind, especially given that most of them are following the FDA’s programs for accelerated approval.
Images via sfam_photo, Meletios Verras / Shutterstock