n a major blow to a new approach to treating cancer, two patients taking an experimental therapy from Juno Therapeutics have died following severe brain swelling, the company said Wednesday. It’s the second time Juno’s experimental therapy has been tied to fatal side effects.
The company has halted the clinical trial, but the latest setback could derail the program entirely.
Over the summer, the Food and Drug Administration stopped the same study after three patients died of cerebral edema, in which fluids flood the brain. At that time, Juno maintained that the problem was not with its product — an infusion of genetically engineered cells — but rather with a cocktail of chemotherapies used to treat patients before they got the experimental therapy. The company removed one of those chemo drugs, called fludarabine, from the cocktail, and the FDA quickly gave Juno the green light to resume the study.
But that does not appear to have solved the problem. One of the patients who died was younger than 30. The company said the other patient was older, but did not give specifics.
With the two new deaths, Juno faces tough questions about the safety of its therapy, called JCAR015. And the FDA will likely come under fire for allowing the company to get back to work just days after the first clinical hold.
Brad Loncar, founder of a cancer immunotherapy fund, said Juno was “going way too fast on this.”
“It’s just terrible,” Loncar said. “They’ve killed a couple of people, and it seems like, in part, it’s because of the rush to judgment.”
Juno is working on cutting-edge cancer immunotherapy, developing treatments made by harvesting a patient’s own immune cells and rewiring them to home in on tumors in the body. Such therapies, called CAR-Ts, have led to some promising early results in certain cancers, but scientists caution that they are only just beginning to understand the field.
It appears that the rapid proliferation of CAR-T cells, once they’ve been injected back into the body, seems to be directly correlated with patients developing cerebral edema, said Dr. Mark Frohlich, Juno’s executive vice president of portfolio strategy. Understanding how this unfolds is now the “big focus” of the company in understanding what went awry with the JCAR015 trial.
“It is our view that the removal of fludarabine has reduced the incidence of severe neurotoxicity,” Juno CEO Hans Bishop said on a call Wednesday morning detailing the halt of the clinical trial. “It just hasn’t gotten us as far as we hoped that it would.”
Juno’s stock plunged 44 percent before trading on it was halted. Further frustrating Juno’s investors, Bishop sold nearly $6 million worth of the company’s stock between its two clinical holds. Each trade was pre-planned and executed legally, federal filings show, but such transactions have long irked outside investors, many of whom took to Twitter to criticize the company Wednesday.
CAR-T therapy may be on the bleeding edge of cancer immunotherapy, but it’s known for its laundry list of highly toxic symptoms. Beyond cerebral edema, patients can also develop a condition called “cytokine release syndrome,” in which the T cells excrete huge quantities of chemicals that lead to severe fevers, nausea, difficulty breathing, low blood pressure, and organ swelling. The worse the cancer, the worse the cytokine storm.
The halted study is testing JCAR015 on adults with acute lymphoblastic leukemia, a rare and deadly form of blood cancer.
Juno is also developing CAR-T therapies for lymphoma and other blood cancers. Adults with acute lymphoblastic leukemia, or ALL, “appear to be the most challenging to balance toxicity and efficacy,” Frolich said.
The alternative for patients with ALL is salvage chemotherapy, which is “infrequently efficacious,” with 11 to 23 percent of patients dying from treatment-related symptoms, said Juno’s chief financial officer, Steve Harr. Ending or delaying the JCAR015 trial means that the patients enrolled will likely have no other options for treatment.
“We all are grasping with how we control this better,” Harr added. “But we need to expect that if we have efficacy in this setting, there will be some toxicity.”
Bishop emphasized in the early-morning conference call that the patients were already quite ill before joining the trial. “These patients have virtually no other options, and have a highly lethal disease,” he said. He said the company’s other clinical trials have not been affected and said Juno is still on track to launch its first drug as early as 2018.
Loncar contended that Juno management still doesn’t have a grasp on why patients have been dying in the JCAR015 trial.
“Regardless of everything they said on that phone call, they have no idea whatsoever,” Loncar said.