One of Kite Phar­ma’s CAR-T pa­tients died from cere­bral ede­ma, trig­ger­ing a safe­ty alarm

Kite Phar­ma re­vealed to­day that one of the pa­tients in their late-stage pro­gram for the CAR-T drug KTE-C19 died from cere­bral ede­ma, the same brain swelling con­di­tion that went on to scut­tle Juno Ther­a­peu­tics’ lead drug.

In a call with an­a­lysts for their Q1 re­port, the close­ly-watched biotech $KITE said that they had in­formed the FDA and there was no pause or halt to the study. The death in late April, though, clear­ly raised a red flag for an­a­lysts af­ter Kite had man­aged to get all the way through a piv­otal pro­gram with­out a death due to cere­bral ede­ma af­ter treat­ing hun­dreds of pa­tients.

David Chang, Kite

“It took about two days of pro­gres­sive­ly wors­en­ing neu­ro­log­i­cal events,” com­ment­ed Kite CMO David Chang. “In this time the pa­tient’s over­all con­di­tion was de­te­ri­o­rat­ing.”

“This pa­tient had re­frac­to­ry non-Hodgkin lym­phoma,” added Chang. “At the time of en­roll­ment he had ex­plo­sive dis­ease that was rapid­ly pro­gress­ing and had a lot of symp­toms from the tu­mor.” There was fever, con­cerns about un­der­ly­ing in­fec­tions – though tests came back neg­a­tive — and “pret­ty rapid­ly pro­gress­ing dis­ease.”

In an email, a spokesper­son for Kite not­ed that “we don’t see any safe­ty con­cerns. All axi-cel and KTE-C19 de­vel­op­ment stud­ies con­tin­ue as planned. As a re­minder, over­all in­ci­dence of KTE-C19 re­lat­ed grade 5 events stands at 2% in ap­prox­i­mate 200 pa­tients treat­ed in our study sup­ports the ben­e­fit of axi-cel and KTE-C19.  If pa­tients treat­ed in the NCI stud­ies are in­clud­ed, over 300 pa­tients have been treat­ed with KTE-C19.”

Kite’s shares dropped 10% as news of the death spread.

Kite had want­ed to fo­cus to­day pri­mar­i­ly on its com­mer­cial­iza­tion plans for this drug, look­ing to a pos­si­ble FDA ap­proval lat­er in the year. But af­ter Juno was forced to shelve JCAR015 af­ter it killed 5 pa­tients who suf­fered cere­bral ede­ma, the news clear­ly cap­tured an­a­lysts’ at­ten­tion.

The FDA quick­ly lift­ed their first clin­i­cal hold on Juno’s drug af­ter the first three deaths, in­di­cat­ing reg­u­la­tors’ al­lowance for the ad­vanced state most of these can­cer pa­tients are in when they get in­to a CAR-T study. When two more pa­tients died soon af­ter the hold was lift­ed, though, that ex­pe­ri­ence could raise ques­tions of whether reg­u­la­tors may have be­come more sen­si­tive to the safe­ty is­sues in­volved with these drugs.

Juno had ini­tial­ly blamed the first group of deaths on the use of flu­dara­bine dur­ing the pre­con­di­tion­ing reg­i­men pa­tients go through to make them more re­cep­tive to cell ther­a­py. So they dropped it, then saw more pa­tients die. The flu/cy com­bo, though, was used by Kite and oth­ers. Kite be­lieves it has just the right mix to gain ef­fi­ca­cy with­out cre­at­ing un­rea­son­able safe­ty is­sues.

These drugs — reengi­neered T cells tak­en from pa­tients and then re­in­fused — have had safe­ty is­sues from the very be­gin­ning, with a num­ber of pa­tients suf­fer­ing from cy­tokine storms that oc­ca­sion­al­ly turned lethal.

Chang said that they would con­tin­ue to con­sid­er the ef­fi­ca­cy and safe­ty of the drug as more stud­ies pro­ceed.

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

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