Juno’s CAR-T drugs didn’t just kill three people in clinical trials. They actually killed 4, as the company notes in its “revised” remarks from last week’s transcript of a call with company analysts. And the followup raises the mystery of yet another case of cerebral edema triggered by severe neurotoxicity, which may or may not have been reported by Juno.
Here’s the statement, posted with the transcript in a filing with the SEC:
Note to Revised Remarks: (Chief Medical Officer Dr. Mark) Gilbert mistakenly said “three” cases out of 129 rather than “four” cases. The fourth case was a patient treated in the JCAR014 trial, which case occurred in a young adult patient with r/r ALL who received flu/cy preconditioning and a higher JCAR014 cell dose than is now used on that trial. This death was included in the data presented in an oral presentation at the American Society of Hematology meeting in December 2015 and included in Juno’s Annual Report on Form 10-K for the fiscal year ended December 31, 2015.
Note to Revised Remarks: As noted earlier in the question and answer session, the FDA also reported an instance of cerebral edema in its database outside of the JCAR015 trial. Juno does not know whether that instance is the same case of cerebral edema as Juno is aware of from the JCAR014 trial, or if it occurred on a trial for a non-Juno product candidate.
Juno triggered a rout among its investors last week when it stunned the market with news that its lead CAR-T drug, JCAR015, had killed three people in clinical studies, triggering a clinical hold of its pivotal study by the FDA. The company immediately blamed the recent addition of the chemo drug fludarabine to precondition patients for the cell therapy and offered to drop the drug. In one of the fastest responses by the FDA in the face of multiple patient deaths, the agency agreed and lifted the hold earlier this week.
The personalized brand of CAR-Ts that Juno, Kite, and Novartis have been developing extract immune cells from patients, re-engineer them with a chimeric antigen receptor and then inject them back into patients, equipped to swarm cancer cells. These new treatments are also known to trigger cytokine release syndrome, which forced a temporary pause in the experimental work a couple of years ago. But Juno believes that the way that fludarabine was used recently caused the neurotoxicity that triggered cases of cerebral edema tracked by investigators.
Not everyone was as quick as the FDA to buy into that theory, though, as several investigators note that fludarabine has been used regularly without evidence of cerebral edemas. In addition, rival Kite Therapeutics has used a low dose of fludarabine in its work and has no plans to change as it pursues its own pivotal work.
The FDA, though, is not explaining anything as of now, declining to answer some specific questions of mine.
“Cellular therapies, including Chimeric Antigen Receptor (CAR) T-Cell therapies, hold great promise in the treatment of serious and life-threatening diseases,” the agency said in a statement to Endpoints. “We therefore do everything possible to assist sponsors in advancing clinical development programs in an effort to bring promising therapies to patients. The FDA recognizes that investigational products intended to treat serious diseases also have the potential to pose risks to patients. To this end, the FDA constantly looks at the risk-benefit profile of experimental therapies and when we have concerns about the risks, we may place the clinical trials on hold.”
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