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

A New Fron­tier: The In­ner Ear

What happens when a successful biotech venture capitalist is unexpectedly diagnosed with a chronic, life-disrupting vertigo disorder? Innovation in neurotology.

That venture capitalist was Jay Lichter, Ph.D., and after learning there was no FDA-approved drug treatment for his condition, Ménière’s disease, he decided to create a company to bring drug development to neurotology. Otonomy was founded in 2008 and is dedicated to finding new drug treatments for the hugely underserved community living with balance and hearing disorders. Helping patients like Jay has been the driving force behind Otonomy, a company heading into a transformative 2020 with three clinical trial readouts: Phase 3 in Ménière’s disease, Phase 2 in tinnitus, and Phase 1/2 in hearing loss. These catalysts, together with others in the field, highlight the emerging opportunity in neurotology.
Otonomy is leading the way in neurotology
Neurotology, or the treatment of inner ear neurological disorders, is a large and untapped market for drug developers: one in eight individuals in the U.S. have moderate-to-severe hearing loss, tinnitus or vertigo disorders such as Ménière’s disease.1 With no FDA-approved drug treatments available for these conditions, the burden on patients—including social anxiety, lower quality of life, reduced work productivity, and higher rates of depression—can be significant.2, 3, 4

Joe Jimenez, Getty

Ex-No­var­tis CEO Joe Jimenez is tak­ing an­oth­er crack at open­ing a new chap­ter in his ca­reer — and that in­cludes a new board seat and a $250M start­up

Joe Jimenez is back.

The ex-CEO of Novartis has taken a board seat on Century Therapeutics, the Versant and Bayer-backed startup focused on coming up with a brand new twist on cell therapies for cancer — a field where Jimenez made his mark backing the first personalized CAR-T approved for use.

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Can we make the an­tibi­ot­ic mar­ket great again?

The standard for-profit model in drug development is straightforward. Spend millions, even billions, to develop a medicine from scratch. The return on investment (and ideally a tidy profit) comes via volume and/or price, depending on the disease. But the string of big pharma exits and slew of biotech bankruptcies indicate that the model is sorely flawed when it comes to antibiotics.

The industry players contributing to the arsenal of antimicrobials are fast dwindling, and the pipeline for new antibiotics is embarrassingly sparse, the WHO has warned. Drugmakers are enticed by greener pastures, compared to the long, arduous and expensive path to antibiotic approval that offers little financial gain as treatments are typically priced cheaply, and often lose potency over time as microbes grow resistant to them.

The FTC and New York state ac­cuse Mar­tin Shkre­li of run­ning a drug mo­nop­oly. They plan to squash it — and per­ma­nent­ly ex­ile him

Pharma bro Martin Shkreli was jailed, publicly pilloried and forced to confront some lawmakers in Washington riled by his move to take an old generic and move the price from $17.50 per pill to $750. But through 4 years of controversy and public revulsion, his company never backed away from the price — left uncontrolled by a laissez faire federal policy on a drug’s cost.

Now the FTC and the state of New York plan to pry his fingers off the drug once and for all and open it up to some cheap competition. And their lawsuit is asking that Shkreli — with several years left on his prison sentence — be banned permanently from the pharma industry.

Amber Saltzman (Ohana)

Flag­ship's first ven­ture of 2020 is out, and it's all about sperm

A couple years ago, Amber Salzman got a call as she was returning East full-time after a two-year stint running a gene therapy company in California.

It was from someone at Flagship Pioneering, the deep-pocketed biotech venture firm. They had a new company with a new way of thinking about sperm. It had been incubating for over a year, and now they wanted her to run it.

“It exactly fit,” Salzman told Endpoints News. “I just thought I had to do something.”

Pfiz­er ax­es 6 ear­ly to late-stage can­cer stud­ies from the pipeline — with one oth­er cut for sick­le cell dis­ease

Pfizer trimmed a group of 3 R&D programs using their PD-L1 Bavencio — partnered with Merck KGaA — in their latest pipeline cull.

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UP­DAT­ED: In­cyte scores much need­ed PhI­II suc­cess — and of course it’s de­liv­ered by rux­oli­tinib

Incyte’s efforts to breathe a second life into ruxolitinib — its JAK inhibitor sold in pill form as Jakafi — has been greeted with clear, if preliminary and unsurprising, Phase III success.

Topline data from the TRuE-AD2 cements ruxolitinib’s foundational importance for Incyte, and gives analysts hope that there might yet be room for growth in a pipeline that’s suffered multiple R&D setbacks.

Stephen Hahn, AP

The FDA un­veils a new reg­u­la­to­ry frame­work to speed along gene ther­a­pies, re­ward­ing the lead­ing play­ers

Bioregnum Opinion Column by John Carroll

The emphasis at the FDA over the past 5 years or so has been on assisting drug developers as much as they can to speed up regulatory reviews and push more drugs into the market. And they are now crafting a final set of regulations aimed at flagging through a whole new generation of gene therapies in clinical testing at a rapid clip.

In a set of 6 prospective guidances posted on the FDA web site Tuesday morning, FDA commissioner Stephen Hahn committed the agency to staying flexible in handing out designations that are critical to gaining early approvals for drugs that claim to be once-and-done but don’t have anything close to the data needed to prove it.

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Mike Bloomberg (AP IMAGES)

Mike Bloomberg joins a grow­ing cho­rus of De­mo­c­ra­t­ic pres­i­den­tial can­di­dates threat­en­ing to go af­ter drug patents

As the mayor of New York City, Mike Bloomberg had a few modest ideas about lowering prescription drug prices in the Big Apple that gained little traction. Now on the campaign trail on a faint hope of clinching the Democratic presidential nomination, the billionaire has some bigger plans — including one that would alter the patent system central to the biopharma business.

In a barebones drug pricing plan posted on Monday, Bloomberg came out blasting President Donald Trump for failing to deliver his promise to lower drug prices, and then making misleading claims about them. The price of over 3,000 drugs still increased at a rate five times higher than inflation in the first six months of 2019, he wrote.