Gene Therapy, R&D

Months after another lethal setback, Juno finally opts to kill lead CAR-T

Juno CEO Hans Bishop

Months after one of the worst setbacks in the recent history of drug development left a string of patients dead, Juno has finally decided that it will terminate its lead drug program, hoping for a better outcome with another CAR-T therapy in its pipeline.

Juno CEO Hans Bishop claimed $JUNO that its decision to shelve JCAR015 was all due to the “unexpected” toxicity that it discovered after the drug killed five patients due to cerebral edema, or brain swelling. The second tally of deaths, though, occurred in November, after the company convinced the FDA to swiftly lift a clinical hold on the drug by making the dubious claim that eliminating fludarabine from the preconditioning regimen for patients would resolve the safety issue that had already killed several late-stage cancer patients.

Fludarabine is still commonly used in most CAR-T studies, needed to help these cell therapies take effect in patients. This first wave of drugs extracts T cells from patients and then reengineers them to go after cancer cells, and progress has been regularly marred by serious safety issues. But there’s still been no clear explanation of why JCAR015 derailed.

Shares of Juno dropped 8% Wednesday evening on the biotech’s reminder of its seriously flawed efforts.

“We continue to experience encouraging signs of clinical benefit in our trial addressing NHL, but we also recognize the unfortunate and unexpected toxicity we saw in our trial addressing ALL with JCAR015,” said Bishop in a statement. “We have decided not to move forward with the ROCKET trial or JCAR015 at this time, even though it generated important learnings for us and the immunotherapy field.”

Juno threw out several vague factors that may have triggered the deaths. But they all added up to a return to Phase I to prove their point. And there was no time to go back to the drawing board. From the statement:

Through the investigation Juno identified multiple factors that may have contributed to this increased risk, including patient specific factors, the conditioning chemotherapy patients received, and factors related to the product. Although Juno believes there are protocol modifications and process improvements that could enable Juno to proceed with JCAR015 in clinical testing in adult r/r ALL, Juno would first need to establish preliminary safety and dose in a Phase I trial. As a result of the timing delay that would entail and Juno’s belief that it has other product candidates in its pipeline that are likely to provide improved efficacy and tolerability,

As just about everyone who follows this field has expected for some time now, Juno is turning to JCAR017, hoping to get back on track after falling far behind the two leaders in the field: Kite and Novartis. In its statement today, Juno outlined plans to launch a pivotal study for r/r diffuse large B cell lymphoma later this year. The biotech, though, has now fallen behind rivals by more than a year.

At one point Juno was considered a contender for a pioneering approval, running neck-and-neck with Kite. Yesterday, though, Kite posted impressive 6-month results for its CAR-T ahead of its application for approval, as Juno was just getting ready to formally terminate its troubled lead program.

Added Bishop:

Looking forward into 2017, we continue to be optimistic about the progress we are making with JCAR017 and our pipeline more broadly. We expect 2017 will be a data-rich year of key insights, based on up to 20 ongoing trials by year end, and we plan to present data from these trials as appropriate throughout the year.

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