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.

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.

Biohaven CEO Vlad Coric (Photo Credit: Andrew Venditti)

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As coro­n­avirus vari­ants trig­ger new alarms, the NIH is putting an un­der-the-radar ‘next-gen’ vac­cine in­to PhI

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The decision, as the initial wave of reactions suggest, could have dramatic implications for where the agency is headed in the next four years — if not beyond.

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