Kite CAR-T Death: An Unwelcome Mystery as FDA Mulls Approval

Xconomy National — 

In a lengthy interview in January, Kite Pharma CEO Arie Belldegrun was adamant that his company’s experimental cell therapy was different from one competitor, Juno Therapeutics, because unlike with Juno, no Kite patient had died from cerebral edema, or massive swelling in the brain.

Belldegrun can no longer make that claim. Kite (NASDAQ: KITE) reported this morning that one patient being treated with its KTE-C19, a cell therapy in development for a variety of deadly blood cancers, died of multiple organ failure and cerebral edema in April. Also known as axicabtagene ciloleucel, the drug is under FDA review as a treatment for advanced cases of non-Hodgkin lymphoma.

It could be the first of a new wave of such therapies known as CAR-T to come to market for difficult-to-treat blood cancers. How far the promise of CAR-T can carry over into long-lasting treatments, however, depends in part on solving the mystery of the cells’ often drastic side effects in patients’ brains.

Investors drove down the company’s share price more than 11 percent to $72.53 in early afternoon trading.

When speaking with Xconomy in January, Belldegrun contrasted KTE-C19 with a treatment from Juno called JCAR-015. At that time, Juno (NASDAQ: JUNO) was mulling whether to pull the plug on JCAR-015, its most advanced therapy, after five patients receiving it had died from the swelling in 2016.

“When you have so many cases of cerebral edema, you understand there’s a problem,” Belledegrun said at the time. “We had zero cases.”

Juno said it would kill the program in March and has not yet discussed more details about the deaths.

The Kite death has reinforced the uncertainty around CAR-T therapies, which use live, genetically modified T cells, the attack soldiers of the immune system, to boost patients’ defenses against cancer. As Xconomy reported in March, doctors who treat leukemia and lymphoma are glad to have the first-generation CAR-Ts as a lifeline for patients with no options left. Large percentages of these patients have seen their cancer disappear, at least for a while, soon after treatment. In the case of KTE-C19, 36 percent of NHL patients had no sign of disease six months after treatment.

But Juno’s mysterious cluster of cerebral edema cases, as well as CAR-T’s potential for other severe, sudden side effects, are likely to limit the therapy until doctors and researchers understand more about how the modified cells work.

Kite chief medical officer David Chang said this morning on a conference call that the death occurred in a 30-patient safety study that was testing measures to reduce the risk of serious side effects from KTE-C19. The patient was “very sick,” said Chang, with “explosive” rapidly progressing NHL.

Kite officials gave no indication this morning that the death would slow down the drug’s timeline. Kite will now warn patients of the risk of cerebral edema.

The FDA is currently considering both KTE-C19 and a CAR-T from Novartis for children with acute lymphoblastic leukemia.

Image of T cell from NIAID via a Creative Commons license.