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

De­vel­op­ment of the Next Gen­er­a­tion NKG2D CAR T-cell Man­u­fac­tur­ing Process

Celyad’s view on developing and delivering a CAR T-cell therapy with multi-tumor specificity combined with cell manufacturing success
Overview
Transitioning potential therapeutic assets from academia into the commercial environment is an exercise that is largely underappreciated by stakeholders, except for drug developers themselves. The promise of preclinical or early clinical results drives enthusiasm, but the pragmatic delivery of a therapy outside of small, local testing is most often a major challenge for drug developers especially, including among other things, the manufacturing challenges that surround the production of just-in-time and personalized autologous cell therapy products.

Paul Hudson, Getty Images

UP­DAT­ED: Sanofi CEO Hud­son lays out new R&D fo­cus — chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

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What does $6.9B buy these days in on­col­o­gy R&D? As­traZeneca has a land­mark an­swer

Given the way the FDA has been whisking through new drug approvals months ahead of their PDUFA date, AstraZeneca and their partners Daiichi Sankyo may not have to wait until Q2 of next year to get a green light on trastuzumab deruxtecan (DS-8201).

The pharma giant this morning played their ace in the hole, showing off why they were willing to commit to a $6.9 billion deal — with $1.35 billion in a cash upfront — to partner on the drug.

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Large advertisements for the drug Vivitrol decorate the walls of Grand Central Station on June 15, 2017 in New York City. (Photo: Andrew Lichtenstein via Getty)

FDA slaps down Alk­er­mes for mis­lead­ing Viv­it­rol ads — don't for­get vul­ner­a­bil­i­ty to opi­oid over­dose

The ads piqued interest as soon as they started appearing in 2016: at Grand Central Station, on the Red Line in Cambridge, and on a billboard off the New Jersey Turnpike. All showed a young person, generally with his or her arms crossed, and the question, “what is Vivitrol?”

Vivitrol’s maker, Alkermes, was in the midst of a marketing and lobbying campaign to promote the anti-opioid addiction drug — a campaign that would face significant backlash for tarnishing competitors despite little evidence for Vivitrol’s superiority.

FDA in-house re­view spot­lights an is­sue with one of Hori­zon's end­points but notes ef­fi­ca­cy for lead drug

The FDA in-house review highlights a disagreement of investigators’ use of a key endpoint by Horizon Pharma in the late-stage trial for the top drug in its pipeline, but largely agreed that the antibody was effective.

Horizon submitted a BLA for thyroid eye disease (TED) drug teprotumumab in March, less than two years after they bought the drug (and the rest of a division) from Narrow River for $145 million upfront. With breakthrough status, priority review, orphan designation and in-house sales projections of up to $750 million, the one-time Roche reject became the marquee pipeline asset for a company that’s developed some of the world’s most expensive drugs.

Seat­tle Ge­net­ics de­tails pos­i­tive OS and PFS da­ta for tu­ca­tinib in breast can­cer

Seattle Genetics $SGEN is showing off more positive data around tucatinib, its pivotal-stage drug for HER2 positive breast cancer.

A month after hearing about solidly upbeat hazard ratios, we learned today that the estimated progression-free survival rate at one year was 33% in the tucatinib arm compared to 12% for patients taking trastuzumab and capecitabine alone.

Median PFS was 7.8 months (95% CI: 7.5, 9.6) in the tucatinib arm, compared to 5.6 months (95% CI: 4.2, 7.1) in the control arm.

Bat­tered, cash hun­gry In­tec feels the burn of No­var­tis re­jec­tion

It’s a case of some bad timing for Intec.

Just when a key trial testing the company’s Accordion drug delivery tech imploded in Parkinson’s disease, they handed Novartis data from a successful PK study of a custom Accordion pill engineered to deliver a Novartis compound to entice the Swiss drugmaker into signing a licensing agreement.

Novartis said thanks, but no thanks.

For the cash-strapped Israeli drug developer, the failure to clinch the deal marks a big blow. As of the third quarter, the company has $15.7 million in cash and equivalents, which HC Wainwright analysts estimate will keep the lights on into mid-2020.

Bris­tol-My­ers shows off a low-pro­file AML con­tender it gained from Cel­gene buy­out — and they’re tak­ing it straight to the FDA

Bristol-Myers Squibb reaped an enormous pipeline with its much-criticized $64 billion megadeal to buy Celgene. And it got a few hidden gems in the deal.

One of those gems was brought out for display on Tuesday, with a late-breaker at ASH on CC-486, which is now being prepped for regulatory filings at the FDA and elsewhere.

Celgene top-lined the positive results in a maintenance setting for acute myeloid leukemia a few months ago, but at ASH investigators pulled back the curtains on the all-important data they believe will give them an advantage in the commercial wars to come.

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De­sert­ed by Astel­las and Mer­ck, lit­tle Cor­re­vio still can't win over FDA pan­el con­cerned with its AFib drug's safe­ty

When the FDA spurned Astellas’ pitch for atrial fibrillation drug vernakalant in 2008, regulators made it abundantly clear that it wasn’t the efficacy they had a problem with — two Phase III trials had shown the drug successfully restored 52% of patients’ heartbeat from irregular to normal — but the cardio safety issues for a drug that was to compete with well established, low-risk options. One licensing deal, one clinical hold and several studies later, the chances of approval aren’t looking any better.