After two patient deaths occurred in a clinical trial of Juno Therapeutics' (JUNO) most advanced drug, the FDA halted enrollment in the company's study of JCAR015 in acute lymphoblastic leukemia patients earlier this month. The trial halt, however, proved to be short-lived.
Regulators quickly gave Juno Therapeutics a green light to restart its trial after management agreed to change the chemotherapy preconditioning regimen used in the study.
Analyst Kristine Harjes and contributor Todd Campbell explain the details behind the trial halt and restart in this segment of The Motley Fool's Industry Focus: Healthcare podcast.
A transcript follows the video.
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This podcast was recorded on Jul. 19, 2016.
Kristine Harjes: On July 8th, the FDA put one of Juno's trials on clinical hold, meaning nobody new can enroll, and you can't give patients the experimental therapy. This was their lead trial. It was their most important CAR-T therapy, called JCAR 015; it's being studied for acute lymphoblastic leukemia, a type of blood cancer. What happened was two patients in the trial died, and the FDA said, "Whoa, whoa, whoa... hold on!"
Todd Campbell: Yeah. In cancer treatment in trials, they're very conscious of the fact that you have a disease that can kill you if it's not treated right; but the treatment has to be safe, too. So they're watching that dynamic very closely.
Harjes: Yeah, especially for earlier studies. This was phase 2, when safety is still a priority.
Campbell: Right. The phase 1 trails that have been done on this drug involve a relatively limited patient pool. Even if you include every trial that's being studied for the CAR-Ts that Juno's working on, you're only talking about 130-ish patients. It's not what you would call a lot of patients that you're trying to evaluate the data on. That being said, it was very surprising to people, because while there have been cases of adverse events, most of those cases have been tied to cytokine release syndrome, even cytokine in some cases, that had been pretty easily corrected by adjusting dosage and stuff like that using corticosteroids, and some of the other things they use to try to keep those in check.
So, the fact that these patients had passed away because of brain swelling, which was the result of neurotoxicity in response to the therapy, that immediately caused the FDA and Juno to say, "Woah, we have to figure this out. We can't enroll any more patients. Let's figure out what caused these deaths. You not only had the two that just happened, but there had been one back in May, and there had been one last fall, who had also passed away in these trials. So we now have four patients who had passed away. Obviously, you need to nail down the cause of that before you put more patients at risk.
Harjes: And it appears that they did nail down what the cause was.
Campbell: Right! Kristine, on the day that they announced that the FDA was putting the trial on hold, they were also announcing, "We believe we know what the problem is."
Campbell: It's crazy how quickly that happened.
Harjes: It really is. It seems like a pretty clear link when they added this new chemotherapy to this trial, thinking it would help these CAR-T cells take hold faster. Instead, they're saying that led to the neurotoxicity that caused the brain swelling.
Campbell: Right. Let's back up a little bit again for our listeners here. These CAR-T drugs -- essentially what we're talking about is reengineering T cells from patients so they can be reintroduced back into the body, seek out and destroy cancer cells by binding to proteins that are expressed on those cancer cells. It's a targeted therapy. It's a brand-new approach or class of drugs. What they've found is, if patients get preconditioned with chemotherapy agents, then these drugs become more efficacious, they work better.
So what Juno was saying caused the deaths was the addition of a chemotherapy agent known as fludarabine to the existing preconditioning regimen. Once they did include that -- we'll call it "flu" for short -- once they started including flu, that's when they started seeing these problems. So they went back to the FDA and said, "What if we just get rid of flu? We won't use flu anymore in the preconditioning regimen." And within days, the FDA had reviewed the documentation and said, "Yep, that's OK, you can continue enrolling, we'll restart the trial. From now on, though, just use that one preconditioning chemotherapy agent."
Harjes: It was really interesting to me to see how quickly that decision turned around. I remember in some of our initial coverage on Fool.com when we saw the red light from the FDA, our writers were saying, "We're not really sure how long it might be before Juno is allowed to proceed." Then, just days later, it was July 13th, that the FDA said, "Yep, you can proceed if you exclude flu, and proceed as we have talked about."
Campbell: Right. The FDA had about 30 days. They could have taken as long as that to review the information, and they did it in a couple days. (laughs) I was one of those writers who was saying, "I don't know, it could take weeks. Who knows how long it'll be?" Obviously, though, the FDA has made a commitment to accelerate in the approval of cancer drugs, especially novel cancer drugs. That's probably why they wasted no time looking at this. The patient population that this drug treats is a tough-to-treat population. It's relapsing and recurring acute lymphoblastic leukemia, ALL patients. These patients have undergone two, three, four different treatments prior to that, so there are not a lot of treatment options available to them.