Juno’s lead CAR-T slammed with a clin­i­cal hold in the last lap ahead of FDA fil­ing

One of Juno’s crit­i­cal stud­ies for its lead CAR-T ther­a­py has just been in­def­i­nite­ly side­lined fol­low­ing the un­ex­plained death of two pa­tients from neu­ro­tox­i­c­i­ty, de­rail­ing the com­pa­ny’s plans to seek mar­ket­ing ap­proval in time for a 2017 launch.

In a nasty sur­prise for share­hold­ers, Juno an­nounced Thurs­day af­ter­noon that the FDA had placed a clin­i­cal hold on its ROCK­ET study, a Phase II clin­i­cal tri­al of JCAR015 in adult pa­tients with re­lapsed or re­frac­to­ry B cell acute lym­phoblas­tic leukemia. That hob­bles the com­pa­ny just as it en­tered the last lap in a tight race with Kite Phar­ma.

The stock $JUNO im­me­di­ate­ly plunged 30%.

In a call with an­a­lysts, Juno CEO Hans Bish­op said that the com­pa­ny no longer ex­pects to get the drug on the mar­ket in 2017. That dead­line has now been pushed to 2018. He al­so said that an­oth­er pa­tient had died of neu­ro­tox­i­c­i­ty in May, but the study con­tin­ued af­ter dis­cus­sions with the FDA. All the pa­tients who died were young.

The biotech in­stant­ly point­ed to the re­cent ad­di­tion of flu­dara­bine as part of the pre-con­di­tion­ing reg­i­men pa­tients un­der­go as a like­ly cause of the deaths. And they have al­ready pro­posed drop­ping that.

“Flu­dara­bine in some ways acts like a dose am­pli­fi­er,” says Bish­op, ex­plain­ing the com­pa­ny’s the­o­ry of what went wrong and trig­gered these cas­es of cere­bral ede­ma.

The FDA has asked for: “A re­vised pa­tient in­formed con­sent form, a re­vised in­ves­ti­ga­tor brochure, a re­vised tri­al pro­to­col, and a copy of the pre­sen­ta­tion made to the agency yes­ter­day.”

All oth­er stud­ies are con­tin­u­ing. And a sub­mis­sion is al­ready ex­pect­ed to be sub­mit­ted this week, un­der­scor­ing the com­pa­ny’s be­lief that it can get the hold lift­ed quick­ly.

There are ab­solute­ly no guar­an­tees, how­ev­er, that that can be done. Zaf­gen has been wait­ing for months for reg­u­la­tors to ad­dress their clin­i­cal hold. And reg­u­la­tors are known for tak­ing their time in re­solv­ing these is­sues.

That’s a huge is­sue for Juno, which was telling re­porters just weeks ago that it was con­fi­dent of fil­ing for an ac­cel­er­at­ed ap­proval in time to get their drug on the mar­ket next year —  rac­ing with Kite to be the first on the mar­ket. It may al­so af­fect oth­er pro­grams as well, if Juno is right. Re­cent re­search has in­di­cat­ed that adding flu­dara­bine im­proves CAR-T cell ex­pan­sion and per­sis­tence, pro­vid­ing what was thought to be an added edge in treat­ing can­cer.

Arch man­ag­ing part­ner and Juno di­rec­tor Robert Nelsen took to Twit­ter to de­fend the com­pa­ny.

 

Juno cap­tured pub­lic at­ten­tion with its pi­o­neer­ing work on CAR-Ts, tak­ing pa­tient cells and adapt­ing them with a chimeric anti­gen re­cep­tor to make them in­to can­cer cell at­tack ve­hi­cles. Ear­ly on in­ves­ti­ga­tors had to ad­just their stud­ies to counter the chance that pa­tients would be hit with a cy­tokine storm as the drug was ad­min­is­tered. This is the first time that neu­ro­tox­i­c­i­ty has halt­ed a CAR-T study.

And where does this leave Kite? Clear­ly in the lead.

The biotech put out a re­lease late Thurs­day as­sert­ing that it com­plet­ed en­rolling pa­tients for its on­go­ing Phase II piv­otal study of KTE-C19, leav­ing it on track for a sub­mis­sion to the FDA by the end of the year.

Lessons for biotech and phar­ma from a doc­tor who chased his own cure

After being struck by a rare disease as a healthy third year medical student, David Fajgenbaum began an arduous journey chasing his own cure. Amidst the hustle of this year’s JP Morgan conference, the digital trials platform Medable partnered with Endpoints Studio to share Dr. Fajgenbaum’s story with the drug development industry.

What follows is an edited transcript of the conversation between Medable CEO Dr. Michelle Longmire and Dr. Fajgenbaum, and it is full of lessons for biotech executives charged with bringing the next generation of medicines to patients.

Christos Kyratsous (via LinkedIn)

He built a MERS treat­ment in 6 months and then the best Ebo­la drug. Now Chris­tos Kyrat­sous turns his sights on Covid-19

TARRYTOWN, NY — In 2015, as the Ebola epidemic raged through swaths of West Africa, Kristen Pascal’s roommates sat her down on their couch and staged an intervention.

“Are you sure this is what you want to be doing with your life?” she recalls them asking her.

Pascal, a research associate for Regeneron, had been coming home at 2 am and leaving at 6 am. At one point, she didn’t see her roommate for a week. For months, that was life in Christos Kyratsous’ lab as the pair led a company-wide race to develop the first drug that could effectively treat Ebola before the outbreak ended. For Pascal, that was worth it.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 72,400+ biopharma pros reading Endpoints daily — and it's free.

Left to right, top to bottom: Carl Gordon, Adam Stone, Peter Moglia, David Schenkein, Robert Nelsen, Carol Gallagher; Srinivas Akkaraju, Ray Debbane, Jim Flynn, Peter Kolchinsky, Thilo Schroeder, Brad Bolzon

UP­DAT­ED: The top 100 bio­phar­ma ven­ture in­vestors at the mega­bil­lions deal ta­ble

The VC crowd took a step back last year, but nevertheless maintained a furious pace of new investments in therapeutic tech platforms and biotech startups. And the top 100 players completely dominated the megabillions game.

Just looking at the number of deals done by each of the top 100, OrbiMed came in at the top, with 20, followed by Alexandria (18), Perceptive (16) and the ubiquitous RA Capital at 16. It’s impossible to say exactly how much they invested in total — those numbers are only rarely provided — but it is clear from the numbers assembled by Chris Dokomajilar at DealForma who’s most likely to be found sitting at the table during the go-go days of biotech investing.

Dokomajilar tracked $14.06 billion in biotech venture investing last year, a dip from the frenzied pace of $16.02 billion in 2018 and more than $10 billion higher than he recorded for 2010, as the economy was recovering from a profound economic crisis.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Rahul Ballal, Imara

As sick­le cell pa­tients find new op­tions, NEA-found­ed Imara pitch­es mid-stage al­ter­na­tive for $86M IPO

November 2019 proved to be a fruitful month for patients with blood disorders known as hemoglobinopathies. Within days, the FDA ushered two drugs for sickle cell disease and another for beta thalassemia to the market — livening up a barren field.

Imara, a relatively young plower, is riding on that enthusiasm as it shoots for an $86.25 million IPO.

Imara emerged from New Enterprise Associates’ orphan drug accelerator Cydan in 2016 as a single-product company. $77.3 million in private financing later IMR-687 remains the sole asset in its pipeline; the difference is the drug is now in Phase II for sickle cell disease, with topline data slated for later this year and two other mid-stage beta thalassemia studies lined up.

RA joins glob­al syn­di­cate to back a $98M round for CAN­bridge

A Beijing-based rare disease and oncology player has raised $98 million to help fund the expansion of its pipeline as well as a commercial portfolio.

CANbridge put out word Tuesday that the global private equity player General Atlantic joined forces with Chinese CRO Wuxi AppTec to lead the Series D, with both ready to chip in an extra $10 million each under the right conditions. The syndicate includes RA Capital Management, Hudson Bay Capital Management, YuanMing Prudence Fund and Tigermed.

Carol Robinson, Professor Dame Carol Robinson Research Group

UP­DAT­ED: Drug dis­cov­ery in HD: Ox­ford spin­of­f's mass spec­trom­e­try ap­proach scores fresh fund­ing

The technology used to detect explosives at airports — mass spectrometry — is being piloted as an engine for drug discovery.

Mass spectrometry is a tool designed to measure with profound accuracy the mass of a single molecule. Typically, mass spectrometers can be used to identify unknown compounds, to quantify known compounds, and to determine the structure and chemical properties of molecules.

UP­DAT­ED: Chi­na ap­proves flu drug be­ing tout­ed as a po­ten­tial coro­n­avirus treat­ment amid a rush of clin­i­cal stud­ies

One of the three drugs that China’s Ministry of Science and Technology has tapped as potential COVID-19 treatments to watch has notched its first Chinese OK — for the flu.

While there’s no proof yet that fapilavir, or favipiravir, is the cure that patients and physicians are yearning for, it stands out for a unique constellation of qualities. It’s been commercially available in Japan for several years (unlike Gilead’s experimental remdesivir) yet it’s new to China (unlike the malaria drug chloroquine phosphate). Perhaps more importantly, a domestic biotech — Zhejiang Hisun Pharma — owns the rights to manufacture and market the drug, preempting any concerns about patents.

FDA goes on high alert as coro­n­avirus rais­es threat to drug man­u­fac­tur­ing and clin­i­cal tri­als grind to a halt

The FDA isn’t quite sure just what the coronavirus outbreak in China will mean for the US pharma industry, but it has the potential to trigger a host of troublesome issues around the supply chain the country is directly plugged into.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 72,400+ biopharma pros reading Endpoints daily — and it's free.

Warren Buffett, AP Images

War­ren Buf­fett gets a dou­ble take as the in­vest­ment pow­er­house set­tles on its first biotech in­vest­ment

Coke. American-Express. Apple. And Biogen?

Warren Buffet’s Berkshire Hathaway, which made itself into a symbol of rock-solid investment strategy, has revealed a stake in the big biotech as it takes on one of the biggest gambles in the industry.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 72,400+ biopharma pros reading Endpoints daily — and it's free.