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.

Scott Gottlieb, AP Images

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