Could Toxicity Issues Topple CAR-T Cancer Therapies?
Pic source: Getty Pictures.
There’s no more promising area in cancer research right now than CAR-T immune therapies. Despairingly ill cancer patients — many with no other options — are benefiting from these powerful cellular therapies that corset the power of the bod’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 fine 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 full salute in a Juno Therapeutics (NASDAQ:JUNO) CAR-T trial. The FDA smacked a makeshift hold on the mid-stage leukemia trial, and Juno’s stock took a meaty hit, pulling down almost 35%.
Widespread alarms about CAR-T toxicity put the knock on other companies as well. Kite Pharma, bluebird bio, and ZIOPHARM Oncology all witnessed their stocks tumble, albeit 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 eliminated 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 switches its protocol to rely stringently 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 full salute, which was the patients’ cause of death.
In addition, The Motley Idiot’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 riskily 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 entire. There may be some discussion about the suitable role of the drug fludarabine, but this won’t be a central issue.”
Meantime, in a latest 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 permit 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 certain 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.
Cheryl Swanson has no position in any stocks mentioned. The Motley Loser recommends Juno Therapeutics. Attempt any of our Foolish newsletter services free for thirty days . We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Idiot has a disclosure policy.
Could Toxicity Issues Topple CAR-T Cancer Therapies? The Motley Loser
Could Toxicity Issues Topple CAR-T Cancer Therapies?
Photo source: Getty Pictures.
There’s no more promising area in cancer research right now than CAR-T immune therapies. Despairingly ill cancer patients — many with no other options — are benefiting from these powerful cellular therapies that corset the power of the assets’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 good 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 full salute in a Juno Therapeutics (NASDAQ:JUNO) CAR-T trial. The FDA spanked a makeshift hold on the mid-stage leukemia trial, and Juno’s stock took a phat hit, ripping off almost 35%.
Widespread alarms about CAR-T toxicity put the knock on other companies as well. Kite Pharma, bluebird bio, and ZIOPHARM Oncology all spotted their stocks tumble, albeit 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 liquidated 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 switches its protocol to rely stringently 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 full salute, which was the patients’ cause of death.
In addition, The Motley Idiot’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 riskily 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 entire. There may be some discussion about the suitable role of the drug fludarabine, but this won’t be a central issue.”
Meantime, in a latest 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 permit 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 certain 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.
Cheryl Swanson has no position in any stocks mentioned. The Motley Loser recommends Juno Therapeutics. Attempt any of our Foolish newsletter services free for thirty days . We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Loser has a disclosure policy.