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

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Feng Zhang (Susan Walsh/AP Images)

In search of new way to de­liv­er gene ed­i­tors, CRISPR pi­o­neer turns to mol­e­c­u­lar sy­ringes

Bug bacteria are ruthless.

Some soil bacteria have evolved tiny, but deadly injection systems that attach to insect cells, perforate them and release toxins inside — killing a bug in just a few days’ time. Scientists, on the other hand, want to leverage that system to deliver medicines.

In a paper published Wednesday in Nature, MIT CRISPR researcher Feng Zhang and his lab describe how they engineered these syringes made by bacteria to deliver potential therapies like toxins that kill cancer cells and gene editors. With the help of an AI program, they developed syringes that can load proteins of their choice and selectively target human cells.

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Dif­fu­sion to hand Nas­daq spot to EIP Phar­ma for PhI­Ib de­men­tia study of ex-Ver­tex drug

One of the more than a dozen bidders for Diffusion Pharmaceuticals’ spot on Nasdaq has prevailed.

Boston biotech EIP Pharma will merge with Diffusion in an all-stock deal, with plans to start a Phase IIb clinical trial in the coming months in a common form of dementia with no approved treatments. The combined company will be renamed CervoMed.

The nine-year-old privately-held EIP is working on a former Vertex drug that it will test in a 160-person Phase IIb in patients with dementia with Lewy bodies, or DLB. The National Institute on Aging is expected to fund that trial with a $21 million grant. With the reverse merger, slated for closing in the middle of this year, EIP will be funded through that readout in the second half of 2024. EIP’s equity and debt holders will own about 77.25% of the combined company.

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Jeff Bluestone (R), Sonoma Biotherapeutics CEO

Jef­frey Blue­stone brings his start­up haul to $400M+, join­ing forces with Re­gen­eron on cell ther­a­pies

These days, when Jeffrey Bluestone gets together with his contemporaries in science, the conversation often turns to retirement plans.

But a little more than three years ago, Bluestone reached a momentous turning point in his career, exiting a prestigious post at UCSF, where he had spent decades in the scientific pursuit of new therapies. And it had nothing to do with retirement anytime in the near future.

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Luke Miels, GSK chief commercial officer

GSK picks up Scynex­is' FDA-ap­proved an­ti­fun­gal drug for $90M up­front

GSK is dishing out $90 million cash to add an antifungal drug to its commercial portfolio, in a deal spotlighting the pharma giant’s growing focus on infectious diseases.

The upfront will lock in an exclusive license to Scynexis’ Brexafemme, which was approved in 2021 to treat a yeast infection known as vulvovaginal candidiasis, except in China and certain other countries where Scynexis already out-licensed the drug.

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Mathai Mammen, FogPharma's next CEO

Math­ai Mam­men hands in J&J's R&D keys to lead Greg Ver­dine’s Fog­Phar­ma 

In the early 1990s, Mathai Mammen was a teaching assistant in Greg Verdine’s Science B46 course at Harvard. In June, the former R&D head at Johnson & Johnson will succeed Verdine as CEO, president and chair of FogPharma, the same month the seven-year-old biotech kickstarts its first clinical trial.

After leading R&D at one of the largest drugmakers in the world, taking the company through more than half a dozen drug approvals in the past few years, not to mention a Covid-19 vaccine race, Mammen departed J&J last month and will take the helm of a Cambridge, MA biotech attempting to go after what Verdine calls the “true emperor of all oncogenes” — beta-catenin.

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CSL CEO Paul McKenzie (L) and CMO Bill Mezzanotte

Q&A: New­ly-mint­ed CSL chief ex­ec­u­tive Paul McKen­zie and chief med­ical of­fi­cer Bill Mez­zan­otte

Paul McKenzie took over as CEO of Australian pharma giant CSL this month, following in the footsteps of long-time CSL vet Paul Perreault.

With an eye on mRNA, and quickly commercializing its new, $3.5 million-per-shot gene therapy for hemophilia B, McKenzie and chief medical officer Bill Mezzanotte answered some questions from Endpoints News this afternoon about where McKenzie is going to take the company and what advances may be coming to market from CSL’s pipeline. Below is a lightly edited transcript.

Boehringer re­ports ro­bust sales led by type 2 di­a­betes and pul­monary drugs, promis­es more to come high­light­ing obe­si­ty

Boehringer Ingelheim reported human pharma sales of €18.5 billion on Wednesday, led by type 2 diabetes and heart failure drug Jardiance and pulmonary fibrosis med Ofev. Jardiance sales reached €5.8 billion, growing 39% year over year, while Ofev took in €3.2 billion, notching its own 20.6% annual jump.

However, Boehringer is also looking ahead with its pipeline, estimating “In the next seven years the company expects about 20 regulatory approvals in human pharma.”

See­los Ther­a­peu­tics 'tem­porar­i­ly' stops study in rare neu­ro dis­or­der for busi­ness rea­sons

Microcap biotech Seelos Therapeutics is halting enrollment of its study in spinocerebellar ataxia type 3 (also known as Machado-Joseph disease) because of “financial considerations,” and in order to focus on other studies, the company said today, adding that the pause would be temporary.

The study will continue with the patients who have already enrolled, and the data from them will be used to decide whether to continue enrolling others in the future.