Juno and the FDA screwed up. Peo­ple died. What now?

Let’s say it plain and sim­ple: Juno Ther­a­peu­tics $JUNO and the FDA screwed up and pa­tients died.

The day ahead of Thanks­giv­ing, Juno man­aged to once again stun its in­vestors with the news that its lead CAR-T, JCAR015, killed two peo­ple. They died from cere­bral ede­mas trig­gered by neu­ro­tox­i­c­i­ty. And the death toll from brain swelling trig­gered by its tox­ic com­bo has now reached six, in­clud­ing a death in a sep­a­rate study.

Yes, these were very sick peo­ple. But you shouldn’t gam­ble with any­one’s life, even if they’re liv­ing un­der a death sen­tence. And that’s ex­act­ly what Juno and the FDA did do, if you strip the case down to the bare es­sen­tials.

Do we re­al­ly know what’s go­ing on here? an an­a­lyst asked Juno ex­ec­u­tives last week.

The an­swer is an ob­vi­ous ‘no.’

It all start­ed on Ju­ly 7,  when Juno ac­knowl­edged the first three deaths and an­nounced the clin­i­cal hold. On Ju­ly 12, the FDA gave them the green light to re­sume the study.

I sus­pect that Juno ini­tial­ly de­cid­ed to fin­ger flu­dara­bine, one of the pre­con­di­tion­ing agents used to help the en­gi­neered cell ther­a­py pop­u­late and make it more ef­fec­tive, be­cause it was the sim­plest and fastest way to present a case that they could quick­ly make their treat­ment rel­a­tive­ly safe. The al­ter­na­tive was to go back to the draw­ing board and start all over, try­ing to gauge just the right mix of drugs. The FDA bought off on it in record time — on­ly three work days lat­er — and lift­ed the clin­i­cal hold.

I’m not say­ing that top Juno ex­ecs or FDA of­fi­cials were du­plic­i­tous or didn’t be­lieve that they were right. That would be a crime. But they were clear­ly wrong, and Juno reck­less­ly jumped back in­to hu­man test­ing with­out be­ing re­quired by reg­u­la­tors to prove their case and make the prop­er ad­just­ments.

Just a ca­su­al scan of the field would raise se­ri­ous ques­tions about Juno’s lethal­ly flawed judg­ment. Flu­dara­bine is com­mon­ly used in cell ther­a­pies, and specif­i­cal­ly in the ri­val CAR-Ts that Juno was rac­ing to get through the clin­ic. (Once Juno fell be­hind Kite, which us­es flu­dara­bine in its mix, CEO Hans Bish­op made much of the fact that this wasn’t race. But I’ll guar­an­tee you that that is ex­act­ly how an­a­lysts and re­porters have been view­ing this all along, with Juno’s en­cour­age­ment as it aimed at first-mover ad­van­tage or a best-in-class run­ner-up po­si­tion.)

Com­ing hot on the heels of the FDA’s de­ci­sion to ap­prove Sarep­ta’s eteplirsen while most agency in­sid­ers still view it as a deeply flawed ex­per­i­men­tal ther­a­py that could al­so be dan­ger­ous for pa­tients, it’s clear that the FDA has slipped the leash of com­mon sense. The pen­du­lum has swung from over­cau­tious to over-ea­ger to ac­com­mo­date bio­phar­ma in 5 years.

It is a dan­ger­ous and dis­turb­ing sit­u­a­tion. But in­stead of log­i­cal­ly ap­ply­ing a more cau­tious ap­proach where need­ed, it’s more than ob­vi­ous that the sen­ti­ment of the new ad­min­is­tra­tion — and Con­gress — is to con­tin­ue to speed de­vel­op­ment re­gard­less of the cir­cum­stances. Let’s be clear, though, that these new drugs won’t be the “cures” that the gen­er­al pub­lic may ex­pect. They can some­times al­so kill. And it won’t al­ways be dead or slow­ly dy­ing pa­tients on the list.

The FDA needs to un­der­take an in­ter­nal re­view and de­ter­mine what went wrong. This should nev­er hap­pen again. As it stands now, it al­most cer­tain­ly will.


Bioreg­num is an opin­ion col­umn from the ed­i­tors of End­points News

Com­mu­ni­cat­ing the val­ue of pre­ci­sion med­i­cine

By Natasha Cowan, Content Marketing Manager at Blue Latitude Health.
Many stakeholders are confused by novel precision medicines, including patients and healthcare professionals. So, how can industry help them to navigate this complexity?

Precision medicine represents a new paradigm in healthcare. It embodies the shift from treating many patients with the same therapy, to having the tools to identify the best treatment for every patient.

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The panel voted unanimously (16 to 0) to support the company’s positive data presentation — backing an OK for expanding the label to include reducing cardio risk. The vote points Amarin $AMRN down a short path to a formal decision by the FDA, with the odds heavily in its favor. Chances are the rest of the questions about the future of this drug will be hashed out in the label’s small print.

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That’s where Takeda finds itself on R&D day today, about 11 months after closing on their Shire acquisition. R&D chief Andy Plump is joining CEO Christophe Weber and other top members of the team to outline a new set of priorities in the greatly expanded pipeline at Takeda, which has jumped into the top ranks of the world’s pharma giants in the wake of the Shire deal.

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BeiGene CEO John Oyler at an Endpoints event in Shanghai, October 2018 (Credit: Endpoints News/PharmCube)

UP­DAT­ED: Chi­na's BeiGene scores first-ever FDA ap­proval — but can they carve up J&J's block­buster fran­chise?

Weeks after Amgen took a $2.7 billion stake in BeiGene, the Beijing-based biotech has secured its first-ever FDA approval for zanubrutinib, a BTK inhibitor, months ahead of schedule.

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GSK's asth­ma bi­o­log­ic Nu­cala scores in rare blood dis­or­der study

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Mer­ck buys a fledg­ling neu­rode­gen­er­a­tive biotech spawned by an old GSK dis­cov­ery al­liance. What’s up with that?

Avalon Ventures chief Jay Lichter has a well-known yen for drug development programs picked up in academia. And what he found in Haoxing Xu’s lab at the University of Michigan pricked his interest enough to launch one of his umbrella biotechs in San Diego.

Xu’s work laid the foundation for Avalon to launch Calporta, which has been working on finding small molecule agonists of TRPML1 (transient receptor potential cation channel, mucolipin subfamily, member 1) for lysosomal storage disorders. And that pathway, they believe, points to new approaches on major market neurodegenerative diseases like Parkinson’s, ALS and Alzheimer’s.

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Carson Block. Muddy Waters via YouTube

Shorts ga­lore: Mud­dy Wa­ters sees slide for Pep­tiDream, tweets con­cerns about Fi­bro­Gen's new da­ta

The short seller Muddy Waters is taking aim at Japan’s most profitable biotech, projecting a slide for a company that has skyrocketed over the last four years. Meanwhile, the firm tweeted out an analysis accusing FibroGen of manipulating data to obscure safety concerns in their latest reveal, although some investors seem satisfied by the biotech’s explanation.

Muddy Waters shorted PeptiDream, a Japanese biotech-for-hire that leveraged its peptide library into partnerships with some of the world’s largest pharmaceutical companies, a 50% profit margin and $6 billion valuation. The firm noted that despite its esteem, PeptiDream has failed to bring a drug to market 13 years after its 2006 launch (although this is not especially rare for biotech).

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Having served in Afghanistan, the navy veteran leading California-based EpicentRx wants to leave no patient behind with his arsenal of anti-cancer drugs. On Thursday, the company was given a $35 million boost to further its mission.

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