And then there were 4: Juno adds an­oth­er vic­tim in CAR-T death tal­ly

Juno’s CAR-T drugs didn’t just kill three peo­ple in clin­i­cal tri­als. They ac­tu­al­ly killed 4, as the com­pa­ny notes in its “re­vised” re­marks from last week’s tran­script of a call with com­pa­ny an­a­lysts. And the fol­lowup rais­es the mys­tery of yet an­oth­er case of cere­bral ede­ma trig­gered by se­vere neu­ro­tox­i­c­i­ty, which may or may not have been re­port­ed by Juno.

Here’s the state­ment, post­ed with the tran­script in a fil­ing with the SEC:

Note to Re­vised Re­marks: (Chief Med­ical Of­fi­cer Dr. Mark) Gilbert mis­tak­en­ly said “three” cas­es out of 129 rather than “four” cas­es. The fourth case was a pa­tient treat­ed in the JCAR014 tri­al, which case oc­curred in a young adult pa­tient with r/r ALL who re­ceived flu/cy pre­con­di­tion­ing and a high­er JCAR014 cell dose than is now used on that tri­al. This death was in­clud­ed in the da­ta pre­sent­ed in an oral pre­sen­ta­tion at the Amer­i­can So­ci­ety of Hema­tol­ogy meet­ing in De­cem­ber 2015 and in­clud­ed in Juno’s An­nu­al Re­port on Form 10-K for the fis­cal year end­ed De­cem­ber 31, 2015.

Note to Re­vised Re­marks: As not­ed ear­li­er in the ques­tion and an­swer ses­sion, the FDA al­so re­port­ed an in­stance of cere­bral ede­ma in its data­base out­side of the JCAR015 tri­al. Juno does not know whether that in­stance is the same case of cere­bral ede­ma as Juno is aware of from the JCAR014 tri­al, or if it oc­curred on a tri­al for a non-Juno prod­uct can­di­date.

Juno trig­gered a rout among its in­vestors last week when it stunned the mar­ket with news that its lead CAR-T drug, JCAR015, had killed three peo­ple in clin­i­cal stud­ies, trig­ger­ing a clin­i­cal hold of its piv­otal study by the FDA. The com­pa­ny im­me­di­ate­ly blamed the re­cent ad­di­tion of the chemo drug flu­dara­bine to pre­con­di­tion pa­tients for the cell ther­a­py and of­fered to drop the drug. In one of the fastest re­spons­es by the FDA in the face of mul­ti­ple pa­tient deaths, the agency agreed and lift­ed the hold ear­li­er this week.

The per­son­al­ized brand of CAR-Ts that Juno, Kite, and No­var­tis have been de­vel­op­ing ex­tract im­mune cells from pa­tients, re-en­gi­neer them with a chimeric anti­gen re­cep­tor and then in­ject them back in­to pa­tients, equipped to swarm can­cer cells. These new treat­ments are al­so known to trig­ger cy­tokine re­lease syn­drome, which forced a tem­po­rary pause in the ex­per­i­men­tal work a cou­ple of years ago. But Juno be­lieves that the way that flu­dara­bine was used re­cent­ly caused the neu­ro­tox­i­c­i­ty that trig­gered cas­es of cere­bral ede­ma tracked by in­ves­ti­ga­tors.

Not every­one was as quick as the FDA to buy in­to that the­o­ry, though, as sev­er­al in­ves­ti­ga­tors note that flu­dara­bine has been used reg­u­lar­ly with­out ev­i­dence of cere­bral ede­mas. In ad­di­tion, ri­val Kite Ther­a­peu­tics has used a low dose of flu­dara­bine in its work and has no plans to change as it pur­sues its own piv­otal work.

The FDA, though, is not ex­plain­ing any­thing as of now, de­clin­ing to an­swer some spe­cif­ic ques­tions of mine.

“Cel­lu­lar ther­a­pies, in­clud­ing Chimeric Anti­gen Re­cep­tor (CAR) T-Cell ther­a­pies, hold great promise in the treat­ment of se­ri­ous and life-threat­en­ing dis­eases,” the agency said in a state­ment to End­points. “We there­fore do every­thing pos­si­ble to as­sist spon­sors in ad­vanc­ing clin­i­cal de­vel­op­ment pro­grams in an ef­fort to bring promis­ing ther­a­pies to pa­tients. The FDA rec­og­nizes that in­ves­ti­ga­tion­al prod­ucts in­tend­ed to treat se­ri­ous dis­eases al­so have the po­ten­tial to pose risks to pa­tients. To this end, the FDA con­stant­ly looks at the risk-ben­e­fit pro­file of ex­per­i­men­tal ther­a­pies and when we have con­cerns about the risks, we may place the clin­i­cal tri­als on hold.”

Illustration: Assistant Editor Kathy Wong for Endpoints News

How Pur­due's $272M ad­dic­tion pay­out fund­ed a new home for its dis­card­ed non-opi­oid re­search

Don Kyle spent more than 20 years working for Purdue Pharma, right through the US opioid epidemic that led to the company’s rise and eventual infamy. But contrary to Purdue’s focus on OxyContin, Kyle was researching non-opioid painkillers — that is, until the company shelved his research.

As the company’s legal troubles mounted, Kyle found an unlikely way to reboot the project. In 2019, he took his work to an Oklahoma State University center that’s slated to receive more than two-thirds of the state’s $272 million settlement with Purdue over claims that the drugmaker’s behavior ignited the epidemic of opioid use and abuse.

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President Joe Biden at the State of the Union address with Vice President Kamala Harris and House Speaker Kevin McCarthy (Patrick Semansky/AP Images)

The drug pric­ing pres­i­dent: Biden warns of ve­to for any IRA re­peal at­tempts

President Joe Biden made clear in his “finish the job” State of the Union address last night that one of those jobs to be finished is insulin prices.

Biden’s push again to tackle insulin prices, after Republicans rebuffed the idea last summer and just after Biden won Medicare drug price negotiations/caps via the Inflation Reduction Act, shows how heavily he’s leaning into this work.

Rupert Vessey, Bristol Myers Squibb head of research and early development

Up­dat­ed: R&D tur­bu­lence at Bris­tol My­ers now in­cludes the end of a $650M al­liance and the de­par­ture of a top re­search cham­pi­on

This morning biotech Dragonfly put out word that Bristol Myers Squibb has handed back all rights to its IL-12 clinical-stage drug after spending $650 million to advance it into the clinic.

The news arrives amid a turbulent R&D stage for the pharma giant, which late last week highlighted Rupert Vessey’s decision to depart this summer as head of early-stage R&D following a crucial three-year stretch after he jumped to Bristol Myers in the big Celgene buyout. During that time he struck a series of deals for Bristol Myers, and also shepherded a number of Celgene programs down the pipeline, playing a major role for a lineup of biotechs which depended on him to champion their drugs.

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Bill Haney, Dragonfly CEO (Dave Pedley/Getty Images for SXSW)

Drag­on­fly chief: Bris­tol My­ers shouldn’t blame IL-12’s clin­i­cal per­for­mance for de­ci­sion to scrap the deal — eco­nom­ics played a key role

Bristol Myers Squibb says the IL-12 drug they were developing out of Dragonfly Therapeutics was scrubbed from the pipeline for a simple reason: It didn’t measure up on clinical performance.

But Bill Haney, the CEO of Dragonfly, is taking issue with that.

The early-stage drug, still in Phase I development, has passed muster with Bristol Myers’ general clinical expectations, advancing successfully while still in Phase I, he says.

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Utpal Koppikar, new Verily CFO

Ex­clu­sive: Ver­i­ly wel­comes Atara Bio­ther­a­peu­tics vet­er­an as new CFO

Verily, Alphabet’s life sciences outfit, has plucked a new CFO from the ranks of Atara Biotherapeutics, the company announced on Wednesday.

Utpal Koppikar joins Verily after a nearly five-year stint as CFO and senior VP at Atara, though his résumé also boasts roles at Gilead and Amgen.

The news follows a major reshuffling at Verily, including several senior departures earlier this year and a round of layoffs.

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Singer Nick Jonas is back at work for Dexcom, this time for its new G7 glucose monitor.

Dex­com's spokescelebri­ty Nick Jonas re­turns to Su­per Bowl in new glu­cose mon­i­tor com­mer­cial

Dexcom is going back to the Super Bowl with its pop singer and patient spokesperson Nick Jonas. Jonas takes center stage as the lone figure in the 30-second commercial showcasing Dexcom’s next-generation G7 continuous glucose monitoring (CGM) device.

Jonas’ sleight-of-hand tricks populate the commercial — he pinches his empty fingers together and pops them open to reveal the small CGM — even as he ends the ad, saying, “It’s not magic. It just feels that way.” Jonas then disappears in a puff of smoke.

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Richard Francis, newly-appointed Teva CEO (Novartis via Facebook)

New Te­va CEO Richard Fran­cis repri­or­i­tizes to 'get back to growth'

Six weeks into his new role at the helm of Teva Pharmaceutical, Richard Francis said it’s time to “get back to growth,” starting with a good look at the company’s priorities.

The chief executive has kicked off a strategic review, he announced during Teva’s quarterly call, which will continue over the next several months and produce results sometime in the middle of 2023. That means some pipeline cuts may be in store, he told Endpoints News, while declining to offer much more detail.

FDA Commissioner Robert Califf on Capitol Hill, Feb. 8, 2023 (Drew Angerer/Getty Images)

FDA com­mis­sion­er floats ideas on how to bet­ter han­dle the pan­dem­ic

FDA Commissioner Rob Califf joined the heads of the CDC and NIH in the hot seat today before a key House subcommittee, explaining that there needs to be a much faster, more coordinated way to oversee vaccine safety, and that foreign biopharma inspections, halted for years due to the pandemic, are slowly ramping up again.

Califf, who stressed to the House Energy and Commerce’s Subcommittee on Health that the CDC also needs better data, made clear that the FDA’s ability to monitor the safety of vaccines “would also benefit greatly by a coordinated federal public health data reporting authority.”

Sanofi is renewing its #VaccinesForDreams campaign with more stories, such as Juan's in Argentina (Sanofi)

Sanofi re­news so­cial cam­paign to re­mind that vac­cines let peo­ple ‘Dream Big’

Sanofi is highlighting people’s dreams — both big and small — to make the point that vaccines make them possible.

The renewed “Dream Big” global social media campaign’s newest dreamer is Juan, a teacher in the Misiones rainforest in Argentina whose story is told through videos on Instagram and Sanofi’s website with the hashtag #VaccinesForDreams.

The campaign ties to Sanofi’s broader umbrella initiative “Vaccine Stories” to promote the value of vaccines and drive awareness of the need for improved vaccination coverage.

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