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Patient Death Triggers FDA Hold For Cellectis’s “Off the Shelf” CAR-T

Xconomy New York — 

[Corrected, 9/18/17, see below] The FDA has forced Cellectis to shut down two Phase 1 trials it has been running to test an “off the shelf” type of cell therapy—a stinging setback to the France- and New York-based company’s aspirations to leapfrog other developers of CAR-T, a type of cancer immunotherapy that the FDA just approved for the first time last week.

Cellectis (NASDAQ: CLLS) said this morning that the FDA stopped the two ongoing trials of prospective cancer therapy UCART123 after a patient in one of those studies died nine days after treatment. Cellectis said the man, a 78-year-old male with blastic plasmacytoid dendritic cell neoplasm, a type of lymphoma, died after experiencing cytokine release syndrome (CRS), a common immune system reaction to CAR-T treatments, that worsened and eventually became fatal.

Because of the patient death and worrisome signs from another patient—a 58-year-old woman with acute myeloid leukemia who also had CRS, though the condition was resolved—a data monitoring committee advised Cellectis on August 28 to lower its dose of UCART123 in both studies. The FDA has now suspended the trials as well.

In a brief statement Tuesday morning, Cellectis said it is “working closely with the investigators and the FDA” to restart testing with an amended protocol and lower doses of UCART123. But the revelation spooked investors, sending shares down roughly 30 percent, to $22.61 apiece, in pre-market trading on Tuesday.

The news comes on the heels of a huge week for a type of cancer immunotherapy treatment known as CAR-T, which soups up a patient’s T cells to go after and kill cancer. Gilead Sciences (NASDAQ: GILD) agreed to buy CAR-T developer Kite Pharma (NASDAQ: KITE) for $12 billion, and then days later the FDA approved the first ever CAR-T treatment, from Novartis, for a type of leukemia. Kite’s own product could follow before the end of the year.

Both of these therapies, however, are what are known as “autologous” therapies. They use a patient’s own cells, meaning each procedure involves extracting those sells, shipping them off to be genetically modified, and putting them back into the patient once they’ve arrived. Cellectis’s therapies are a potential threat to autologous CAR-T developers because the company is developing an “allogeneic” treatment, using T cells drawn from the blood of any donor. If it were to work, allogeneic CAR-T treatments could be quicker and easier to develop and almost certainly cheaper than their autologous counterparts. Novartis’s therapy, for example, costs $475,000 for a one-time treatment, putting it squarely in the national debate over drug prices.

Pfizer bought into Cellectis’s approach. It acquired a 10 percent stake in the company and splits, with Servier, rights to a different Cellectis therapy, UCART19. And some early results were promising. UCART19 put the acute lymphoblastic leukemia of two British children into remission in two compassionate use cases in 2015. “We wanted to look for the next big leap in the field,” Pfizer vice president of CAR-T research Barbra Sasu told Xconomy previously. “We saw that to be the allogeneic approach.”

The potential problem with allogeneic treatments is the fear they may cause a catastrophic immune system reaction between the foreign cells and the patient. Cellectis hasn’t seen this happen so far, however, in humans. The safety problems in the UCART123 study were related to issues developers of autologous CAR-T have often seen in their own studies, not graft-versus-host disease. [A previous version of this story implied that the Cellectis therapy triggered graft-versus-host disease. We regret the error.]