- Juno Therapeutics on Wednesday voluntarily halted a Phase 2 study of its lead CAR-T therapy, called JCAR015, after two patients in the trial suffered cerebral edema. Both patients had died by Wednesday morning.
- These new patient deaths come only a few months after the Food and Drug Administration placed a clinical hold on the same study following three earlier deaths, also from cerebral edema. The so-called "ROCKET" trial is testing JCAR015 in adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL).
- While the initial hold was quickly reversed after Juno removed a pre-conditioning chemo agent from the treatment protocol, Juno's options for moving forward with JCAR015 are now much more limited. Speaking on a call Wednesday morning, CEO Hans Bishop said one option could include terminating the program.
Juno is still reviewing the data surrounding the new patient deaths, and plans to give an update at the upcoming meeting of the American Society of Hematology in early December.
Still, Bishop laid out three potential options for JCAR015: continuing ROCKET under a modified trial protocol; beginning a new study entirely or terminating the program.
The FDA appeared to be quickly convinced by Juno's explanation for the patient deaths in July, allowing the company to restart the study only five days after placing the hold. This time, though, Juno will likely face more challenging questions about the relationship between cerebral edema and JCAR015 itself.
In July, Juno attributed the deaths to the interaction between the pre-conditioning chemo regimen — consisting of fludarabine and cyclophosphamide — and the CAR-T cells reinfused back into the patient. Since then, 12 new patients have been treated with JCAR015 after receiving a pre-conditioning course of cyclophosphamide alone. The two patients who died were treated just last week.
Juno executives did not yet have an answer for what factor triggered the new deaths, although chief medical officer Mark Gilbert noted the recent cases of cerebral edema followed a similar clinical course as those in July.
Terminating JCAR-15, or launching a new trial, would be a costly failure for the CAR-T company and would likely prompt further scrutiny into the safety profile of the promising treatment class.
Juno had already begun to emphasize its second generation CAR-T programs, led by JCAR017, before Wednesday's tragedy. Both Bishop and Gilbert continued in that vein on the conference call, pointing to the (so far) cleaner safety profile of those treatments.
Investors weren't swayed however, sending Juno stock diving by more than 25% in early trading Wednesday morning. Shares in other CAR-T developers, such as Kite Pharma and Cellectis, also fell, reflecting broader concerns about the class.