There's no more promising area in cancer research right now than CAR-T immune therapies. Desperately ill cancer patients -- many with no other options -- are benefiting from these powerful cellular therapies that harness the power of the body's own immune system to fight the disease. The near-miraculous treatments have shown a 70%-80% rate of total remissions, but they still come with great risk.
Just how dangerous the cutting edge of science is for both investors and patients was proved again last month when three patients died from brain swelling in a Juno Therapeutics (NASDAQ:JUNO) CAR-T trial. The FDA slapped a temporary hold on the mid-stage leukemia trial, and Juno's stock took a huge hit, dropping almost 35%.
Widespread alarms about CAR-T toxicity put the knock on other companies as well. Kite Pharma, bluebird bio, and ZIOPHARM Oncology all saw their stocks tumble, although none suffered as badly as Juno.
Juno comes up with a fix -- sort of
The FDA clinical hold was lifted a few days later after the cause of the deaths was traced to a specific chemo called fludarabine being used in the trial as preconditioining prior to CAR-T cell infusion. Juno removed fludarabine from the trial and was quickly given the green light again by the FDA, but investors have shown mixed reactions to the news. Juno's stock hasn't fully recuperated yet. Neither have the stocks of the other CAR-T-focused biotechs. "Investors right now, I think, are kind of -- and deservedly -- on pins and needles ... as the FDA looks at this," said Brad Loncar, a Juno investor and fund manager.
But what if Juno is wrong?
The fatalities in the Juno trial involved patients who had taken fludarabine as part of their preconditioning regimen. So, Juno's theory is that if it changes its protocol to rely strictly on chemo agent cyclophosphamide for preconditioning, there should be no further issues.
Some experts are still skeptical, however. Those include Dr. Sally Church, who writes the Biotech Strategy Blog. In her blog, she pointed out that fludarabine is a common chemotherapy drug. She also said that in previous CAR-T trials where it was used, it was not linked with cerebral edema, or brain swelling, which was the patients' cause of death.
In addition, The Motley Fool's Todd Campbell said recently that there have been occurrences of life-threatening cytokine responses in CAR-T treatment that could raise some questions about their safety down the road. According to the National Cancer Institute, infused T cells release cytokines, which can lead to dangerously high fevers and a precipitous drop in blood pressure.
No final answers, but CAR-T racing ahead
Dr. Stephan Grupp, who is running a similar trial funded by Novartis to treat children with leukemia, doesn't fret about the future of CAR-T therapies. He pointed out that CAR-T is only a few years old, and scientists are still putting together results on the treatment's efficacy and toxicity: "Right now, I don't see this affecting other CAR-T trials, or the field as a whole. There may be some discussion about the appropriate role of the drug fludarabine, but this won't be a central issue."
Meanwhile, in a recent Reuters interview, Juno said it had a shot at receiving initial regulatory approvals for its CAR-T therapy next year, as it had planned before the fatal trial. Previously, the company said the soonest an approval could be won for the drug in question was in 2018.
Speed breeds mistakes, but it also can be reassuring. Juno investors can take heart in the FDA's swift decision to allow the biotech to resume its trial. This suggests the agency believes Juno was correct in identifying the chemo, not its CAR-T therapy, as the cause of death. The rapidity of the decision also suggests the FDA is confident in the potential of CAR-T. But you can be sure it will be watching, and it will take a very dim view of any further fatalities.