Juno Halts CAR-T Cancer Trial After Three Patient Deaths

Juno Halts CAR-T Cancer Trial After Three Patient Deaths July 8, 2016
By Mark Terry, BioSpace.com Breaking News Staff

Seattle – Juno Therapeutics announced yesterday that after three deaths in its Phase II clinical trial of JCARO15, a CAR-T therapy for patients with relapsed or refractory B cell acute lymphoblastic leukemia, the U.S. Food and Drug Administration (FDA) has placed a clinical hold on the trial.

The first patient died in May, but Hans Bishop, the company’s chief executive officer, said in a conference call yesterday that there were “confounding factors and a change in plans was not warranted.”

That patient, in addition to JCAR015, had also received a chemotherapeutic, fludarabine. At the time of the first patient’s death, a connection to fludarabine, which had been added to the clinical trial protocol, was not made. But last week, two additional patients died, both having received fludarabine as part of the treatment protocol, and all three died from cerebral edema, or swelling in the brain caused by excess fluid.

In the trial, patients are first given a cocktail of chemotherapy drugs that kills their existing T-cells, a type of white blood cell in the immune system. Then the patient is administered new T-cells that have been genetically engineered to specifically attack the patient’s cancer. Previous studies have found that by killing the previous T-cells, the new T-cells take hold better, and in addition, adding fludarabine to the cocktail helps even more. Which is why, part of the way through the trial, Juno began adding fludarabine to the regimen.

About 20 people have been enrolled in the trial so far, with up to 90 volunteers planned. Only a small percentage of the 20 have received fludarabine.

Juno has asked the FDA to allow them to continue the trial without fludarabine, and only with cytoxan and JCAR015, as was the case in the earlier parts of the trial. The trial was performed at Memorial Sloan-Kettering Cancer Center, and had a complete response rate of approximately 80 percent.

Juno has also submitted four documents to the FDA—a modified protocol without fludarabine, updated information for investigators, updated patient consent forms, as well as a presentation that was given yesterday at the teleconference. The FDA says it will review them quickly. A typical review would take about 30 days.

Perhaps not surprisingly, Juno took a hit, dropping by up to 35 percent. If the hold is lifted relatively quickly, final approval could potentially be delayed to as late as 2018, assuming approval is in the cards—and assuming the hold gets lifted at all, although it sounds likely.

There are currently three other big competitors, Kite Pharma , Bluebird Bio and Ziopharm Oncology in the CAR-T space. Their share prices dropped a little as well, Kite’s by 7.2 percent to $48.33, Bluebird’s 4.7 percent to $46.52 and Ziopharm by 3.8 percent to $5.78.

David Chang, Kite’s chief medical officer, told Bloomberg yesterday, “Our program is on track and it is unaffected by today’s news. We believe that we have done all the due diligence a company should do, including for the chemo-conditioning dose.”

Kite, for its part, jumped at Juno’s problems, publishing a press release only a couple hours after Juno’s disclosures to tout the completion of enrollment in its CAR-T clinical study. As Adam Feuerstein writes for TheStreet, “It’s hard to believe the timing of Kite’s press release was coincidental, but even if it was, that’s playing ugly.”

Although CAR-T therapy is interesting and certainly holds promise, there are different approaches being explored by other companies, notably bispecific antibodies. Roche is focused on that area, staying out of the CAR-T arena entirely, and Amgen ’s Blincyto is a bispecific antibody.

Immuno-oncology therapy is definitely the hot new area, and it shows incredible promise, but if anything, this setback for Juno is a warning that science out on the cutting edge can be a dangerous and volatile place.

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