Juno’s lead CAR-T slammed with a clin­i­cal hold in the last lap ahead of FDA fil­ing

One of Juno’s crit­i­cal stud­ies for its lead CAR-T ther­a­py has just been in­def­i­nite­ly side­lined fol­low­ing the un­ex­plained death of two pa­tients from neu­ro­tox­i­c­i­ty, de­rail­ing the com­pa­ny’s plans to seek mar­ket­ing ap­proval in time for a 2017 launch.

In a nasty sur­prise for share­hold­ers, Juno an­nounced Thurs­day af­ter­noon that the FDA had placed a clin­i­cal hold on its ROCK­ET study, a Phase II clin­i­cal tri­al of JCAR015 in adult pa­tients with re­lapsed or re­frac­to­ry B cell acute lym­phoblas­tic leukemia. That hob­bles the com­pa­ny just as it en­tered the last lap in a tight race with Kite Phar­ma.

The stock $JUNO im­me­di­ate­ly plunged 30%.

In a call with an­a­lysts, Juno CEO Hans Bish­op said that the com­pa­ny no longer ex­pects to get the drug on the mar­ket in 2017. That dead­line has now been pushed to 2018. He al­so said that an­oth­er pa­tient had died of neu­ro­tox­i­c­i­ty in May, but the study con­tin­ued af­ter dis­cus­sions with the FDA. All the pa­tients who died were young.

The biotech in­stant­ly point­ed to the re­cent ad­di­tion of flu­dara­bine as part of the pre-con­di­tion­ing reg­i­men pa­tients un­der­go as a like­ly cause of the deaths. And they have al­ready pro­posed drop­ping that.

“Flu­dara­bine in some ways acts like a dose am­pli­fi­er,” says Bish­op, ex­plain­ing the com­pa­ny’s the­o­ry of what went wrong and trig­gered these cas­es of cere­bral ede­ma.

The FDA has asked for: “A re­vised pa­tient in­formed con­sent form, a re­vised in­ves­ti­ga­tor brochure, a re­vised tri­al pro­to­col, and a copy of the pre­sen­ta­tion made to the agency yes­ter­day.”

All oth­er stud­ies are con­tin­u­ing. And a sub­mis­sion is al­ready ex­pect­ed to be sub­mit­ted this week, un­der­scor­ing the com­pa­ny’s be­lief that it can get the hold lift­ed quick­ly.

There are ab­solute­ly no guar­an­tees, how­ev­er, that that can be done. Zaf­gen has been wait­ing for months for reg­u­la­tors to ad­dress their clin­i­cal hold. And reg­u­la­tors are known for tak­ing their time in re­solv­ing these is­sues.

That’s a huge is­sue for Juno, which was telling re­porters just weeks ago that it was con­fi­dent of fil­ing for an ac­cel­er­at­ed ap­proval in time to get their drug on the mar­ket next year —  rac­ing with Kite to be the first on the mar­ket. It may al­so af­fect oth­er pro­grams as well, if Juno is right. Re­cent re­search has in­di­cat­ed that adding flu­dara­bine im­proves CAR-T cell ex­pan­sion and per­sis­tence, pro­vid­ing what was thought to be an added edge in treat­ing can­cer.

Arch man­ag­ing part­ner and Juno di­rec­tor Robert Nelsen took to Twit­ter to de­fend the com­pa­ny.

 

Juno cap­tured pub­lic at­ten­tion with its pi­o­neer­ing work on CAR-Ts, tak­ing pa­tient cells and adapt­ing them with a chimeric anti­gen re­cep­tor to make them in­to can­cer cell at­tack ve­hi­cles. Ear­ly on in­ves­ti­ga­tors had to ad­just their stud­ies to counter the chance that pa­tients would be hit with a cy­tokine storm as the drug was ad­min­is­tered. This is the first time that neu­ro­tox­i­c­i­ty has halt­ed a CAR-T study.

And where does this leave Kite? Clear­ly in the lead.

The biotech put out a re­lease late Thurs­day as­sert­ing that it com­plet­ed en­rolling pa­tients for its on­go­ing Phase II piv­otal study of KTE-C19, leav­ing it on track for a sub­mis­sion to the FDA by the end of the year.

A fa­vorite in Alex­ion’s C-suite is leav­ing, and some mighty sur­prised an­a­lysts aren’t the least bit hap­py about it

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