Josh Lehrer, Graphite Bio CEO

Up­dat­ed: Sick­le cell gene edit­ing start­up halts tri­al af­ter flag­ging se­ri­ous side ef­fect in first pa­tient

The first-ever pa­tient to be treat­ed with a new, gene-edit­ed stem cell ther­a­py be­ing de­vel­oped for sick­le cell dis­ease ex­pe­ri­enced a se­ri­ous side ef­fect, forc­ing the drug­mak­er to halt the tri­al.

Graphite Bio said it vol­un­tar­i­ly paused fur­ther dos­ing in the Phase I/II CEDAR tri­al af­ter con­clud­ing that the se­ri­ous ad­verse event is like­ly re­lat­ed to its ther­a­py, nu­la­be­glo­gene au­to­gedtem­cel (nu­la-cel). It al­so re­port­ed the event to the FDA.

Specif­i­cal­ly, the pa­tient, who was dosed in Au­gust, saw pro­longed low blood cell counts, or pan­cy­tope­nia, “re­quir­ing on­go­ing trans­fu­sion and growth fac­tor sup­port.”

“The pa­tient re­mains en­rolled in the CEDAR study and con­tin­ues to re­ceive care and close mon­i­tor­ing from the clin­i­cal in­ves­ti­ga­tor and study staff,” a spokesper­son wrote in re­sponse to an End­points News in­quiry. “We are in close con­tact with the clin­i­cal site and are mon­i­tor­ing the pa­tient’s sta­tus. Out of con­sid­er­a­tion for the pa­tient’s pri­va­cy, ad­di­tion­al de­tails about the pa­tient can­not be dis­closed at this time.”

While the tri­al is on hold, Graphite Bio said it is tak­ing a thor­ough look at the ad­verse event, an­a­lyz­ing risk fac­tors and mit­i­ga­tion strate­gies — with mod­i­fi­ca­tions to the nu­la-cel man­u­fac­tur­ing process al­so on the ta­ble.

“The com­pa­ny’s ini­tial in­ves­ti­ga­tion has ruled out com­mon caus­es of post-trans­plant pan­cy­tope­nia such as a vi­ral in­fec­tion and au­toim­mu­ni­ty, lead­ing to the con­clu­sion that it is like­ly due to treat­ment with nu­la-cel it­self,” Cowen an­a­lyst Phil Nadeau wrote af­ter talk­ing to the ex­ecs.

Sev­er­al oth­er com­pa­nies have set out to treat sick­le cell dis­ease — which is caused by de­fec­tive red blood cells and marked by painful episodes — via the same ap­proach of edit­ing genes in stem cells and then putting them back in­to the pa­tient. But while Ver­tex/CRISPR and Ed­i­tas seek to fix the prob­lem by ac­ti­vat­ing a fe­tal he­mo­glo­bin gene in cells, Graphite Bio’s idea is to cor­rect the mu­tat­ed adult he­mo­glo­bin us­ing its own set of CRISPR-in­spired tools, com­ing from aca­d­e­m­ic pi­o­neers such as Maria Grazia Ron­car­o­lo and Matthew Por­teus.

“At the DNA lev­el, we’re mak­ing stem cells nor­mal again,” was how CEO Josh Lehrer de­scribed the ap­proach back in 2021.

Mani Foroohar of SVB Se­cu­ri­ties wrote that the com­pa­ny is now in­ves­ti­gat­ing whether that fun­da­men­tal ap­proach could’ve caused the side ef­fect. Oth­er hy­pothe­ses in­clude “the qual­i­ty of the pa­tients’ un­der­ly­ing bone mar­row,” Graphite’s tech­nol­o­gy and its use of AAV6 as a de­liv­ery vec­tor.

“Giv­en this num­ber of de­grees of free­dom in any eval­u­a­tion, de­ter­min­ing the prop­er rem­e­dy with a high enough de­gree of con­fi­dence to dri­ve a re­turn to treat­ing pa­tients will be a pro­longed and un­cer­tain process,” he wrote.

While the com­pa­ny had pre­vi­ous­ly hoped to de­liv­er proof-of-con­cept da­ta from 15 pa­tients in mid-2023, it’s now push­ing back that time­line.

Ed­i­tor’s note: Up­dat­ed to in­clude com­ment from Graphite Bio.

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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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.”

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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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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