Juno Therapeutics announced last week that it was placing a voluntary hold on its clinical trial of JCAR015 — an experimental but promising immunotherapy treatment for patients with advanced leukemia — after two patients in the trial died of cerebral edema, or brain swelling.
JCAR015 is Juno’s flagship product, and the most advanced clinical trial the company is currently pursuing. The recent deaths throw the future of the therapy into doubt and highlight the uncertainty surrounding immunotherapy treatments.
In a conference call with analysts Wednesday morning, Juno CEO Hans Bishop said that “all options remain on the table” for the JCAR015 program, including modifying the study, beginning an entirely new study, or possibly “terminating the program.”
The trial was previously put on hold in July, after three patients died of cerebral edema, but was reinstated only five days later after a chemotherapy drug suspected of causing the deaths was removed.
The future of the program likely depends on what information Juno is able to learn from the most recent patient deaths, as well as the FDA’s response to them. Some healthcare analysts have criticized the FDA’s decision to reinstate the trial so quickly in July, particularly because of the apparent similarities between the new deaths and those that caused the July hold.
If JCAR015 continues to be tested, either in a modified study or an entirely new study, the FDA would have to give it the go-ahead once again, which could take months or years. That route also faces uncertainty due to anticipated shake-ups in the organization from the incoming Trump administration, as well as possible changes stemming from the 21st Century Cures Act.
The financial markets have also been uncertain in their reaction to the hold. Juno’s stock plunged 44 percent in early trading Wednesday before rising to $20.50, a drop of 26 percent on the day. Since then, its stock price has bounced between $21 and $22.50, sitting at $22.07/share on Monday morning. Those are the lowest share prices the company has seen since its IPO just under two years ago.
J.P. Morgan analyst Cory Kasimov told investment site Smarter Analyst that the recent hold, while disappointing, is not altogether unsurprising. “As we noted at the time of the first clinical hold: the issues that have popped up in this trial highlight just how early this technology is in its evolution, and the number of important unanswered Qs that remain,” Kasimov said.
Uncertainty is expected in clinical trials, particularly of cutting-edge therapies like CAR-T immunotherapy, but the promise of these drugs continued to drive their development.
Kasimov isn’t betting on the program being terminated — he noted in the same piece that he now predicts JCAR015’s chances of success to be 35 percent.
While immunotherapies remain experimental and uncertain, the promise of such drugs cannot be overstated. An early study of JCAR014, another Juno product, found that certain doses of the drug yielded high response and remission rates among leukemia patients, and immunotherapy treatments in development could provide hope of a cure for thousands of terminally ill cancer patients.