CAR-T

Lethally severe neurotoxicity continues to haunt Juno’s CAR-T pipeline

With the oncology world looking for an update on the leading CAR-T players at ASH after Juno Therapeutics $JUNO put its lead program for JCAR015 back on clinical hold following 2 new deaths from cerebral edema, the biotech was forced to concede Saturday that investigators had tracked 6 cases of severe, grade 3-5 neurotoxicity out of 24 patients in a separate JCAR014 trial for chronic lymphocytic leukemia. And one of the patients died after developing grade 5 cytokine release syndrome and cerebral edema (brain swelling).

On the upside, 15/17 (88%) of evaluable patients had a complete marrow response by flow cytometry. “Fourteen of the complete bone marrow response patients had a response assessment by the more sensitive method of IgH deep sequencing, with 7/14 (50%) having no detectable disease. All seven of these patients are alive and progression free with follow-up ranging from 3 to 26 months.”

Juno has already noted a death from cerebral edema in a patient taking JCAR014 late last year. Another 5 have occurred among the JCAR015 group. The total number of deaths linked to cerebral edema in the JCAR014 and JCAR015 trials is now 7.

The most recent death involved a patient who had received a cy/flu conditioning regimen. Juno had removed fludarabine from its mix for JCAR015 in the summer, telling analysts and the FDA that the elimination of flu would prevent the threat of cerebral edemas. But it didn’t work, leaving the company under a cloud as it attempts to explain what went wrong, and how it might affect the rest of their work.

Juno has been using its clinical work on JCAR014 to inform researchers on how to proceed with JCAR017, a similar treatment that may well soon be the lead program if the biotech opts to scrap the troubled JCAR015, which looms as a distinct possibility.


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RAPS Regulatory Convergence 2017