#ASH17: The BC­MA-tar­get­ed CAR-T bb2121 from blue­bird and Cel­gene takes a star turn in the spot­light

A few days ago, Cel­gene $CELG launched the piv­otal Phase II/III study that will dic­tate the fu­ture of the BC­MA-tar­get­ing bb2121, the CAR-T in-li­censed from blue­bird bio $BLUE. And if they come close to the da­ta that blue­bird has on of­fer at ASH this week­end, this drug will go on to blaze a big trail in the mar­ket as the de­vel­op­ers move on to the next big fo­cus in the field of en­gi­neered T cells.

In­ves­ti­ga­tors in the Phase Ib study out­lined a 94% over­all re­sponse rate for bb2121, with a jaw-drop­ping 56% com­plete re­sponse rate among a small group of 18 pa­tients in heav­i­ly pre­treat­ed ac­tive dose co­horts. Three of those 10 CRs, though, were un­con­firmed at the time of the pre­sen­ta­tion in At­lanta.

The me­di­an pro­gres­sion-free re­sponse rate had yet to be reached. But the 6- and 9-month PFS marks were passed with 81% and 71% rates.

Nick Leschly

“This is what we all dream about,” says blue­bird CEO Nick Leschly, “this kind of da­ta for pa­tients that are in a re­al­ly, re­al­ly tough po­si­tion.”

Blue­bird’s stock jumped 24% in pre-mar­ket trad­ing Mon­day, with Cel­gene {$CELG) up close to 5%.

To be sure there was plen­ty of tox­i­c­i­ty on the dose rang­ing study, with an ad­vanced pa­tient with a pun­ish­ing tu­mor bur­den ex­pe­ri­enc­ing grade 4 neu­ro­tox­i­c­i­ty with cere­bral ede­ma and sub­arach­noid he­m­or­rhage af­ter get­ting the high dose: 450 x 106 CAR+ T cells. And there were a num­ber of cas­es of cy­tokine re­lease syn­drome, a hall­mark of these first gen­er­a­tion CAR-Ts go­ing through the clin­ic.

Cel­gene will now take 150 to 300 mil­lion cell dos­es in­to the land­mark study with about 80 pa­tients, look­ing to see large­ly if it can repli­cate any­thing sim­i­lar. If they are suc­cess­ful, the part­ners can look for­ward to a block­buster mar­ket for one of the most wide­ly an­tic­i­pat­ed late-stage stud­ies in on­col­o­gy.

David David­son

The da­ta un­der­score the po­ten­tial of BC­MA as a tar­get in the field, which is see­ing the first pi­o­neers hit the mar­ket by hit­ting CD19 with ma­jor ef­fect. The da­ta will cer­tain­ly bright­en the stage for blue­bird and Cel­gene, the clear lead­ers in the field, as a bevy of ri­vals fol­low up in hopes of catch­ing or leapfrog­ging the fron­trun­ners.

Juno, mak­ing a CAR-T come­back with JCAR017, just bagged a gam­ma sec­re­tase in­hibitor from Eli Lil­ly for its BM­CA ther­a­py, adding IP agree­ments with the Fred Hutch and On­co­Track­er on their com­bo ap­proach.

But blue­bird isn’t sit­ting still. It’s al­so snap­ping up new tech to keep its cut­ting edge, like the CAR-en­gi­neered gam­ma delta T cell pact it struck with Scot­land’s TC Bio­Pharm a few days ago.

“We’ve got all cylin­ders fir­ing,” says David David­son, the blue­bird chief med­ical of­fi­cer.

Donald and Melania Trump watch the smoke of fireworks from the South Lawn of the White House on July 4, 2020 (via Getty)

Which drug de­vel­op­ers of­fer Trump a quick, game-chang­ing ‘so­lu­tion’ as the pan­dem­ic roars back? Eli Lil­ly and Ab­Cellera look to break out of the pack

We are unleashing our nation’s scientific brilliance and will likely have a therapeutic and/or vaccine solution long before the end of the year.

— Donald Trump, July 4

Next week administration officials plan to promote a new study they say shows promising results on therapeutics, the officials said. They wouldn’t describe the study in any further detail because, they said, its disclosure would be “market-moving.”

— NBC News, July 3

Something’s cooking. And it’s not just July 4 leftovers involving stale buns and uneaten hot dogs.

Over the long weekend observers picked up signs that the focus in the Trump administration may swiftly shift from the bright spotlight on vaccines being promised this fall, around the time of the election, to include drugs that could possibly keep patients out of the hospital and take the political sting out of the soaring Covid-19 numbers causing embarrassment in states that swiftly reopened — as Trump cheered along.

So far, Gilead has been the chief beneficiary of the drive on drugs, swiftly offering enough early data to get remdesivir an emergency authorization and into the hands of the US government. But their drug, while helpful in cutting stays, is known for a limited, modest effect. And that won’t tamp down on the hurricane of criticism that’s been tearing at the White House, and buffeting the president’s most stalwart core defenders as the economy suffers.

We’ve had positive early-stage vaccine data, most recently from Pfizer and BioNTech, playing catchup on an mRNA race led by Moderna — where every little sign of potential trouble is magnified into a lethal threat, just as every advance excites a frenzy of support. But that race still has months to play out, with more Phase I data due ahead of the mid-stage numbers looming ahead. A vaccine may not be available in large enough quantities until well into 2021, which is still wildly ambitious.

So what about a drug solution?

Trump’s initial support for a panacea focused on hydroxychloroquine. But that fizzled in the face of data underscoring its ineffectiveness — killing trials that aren’t likely to be restarted because of a recent population-based study offering some support. And there are a number of existing drugs being repurposed to see how they help hospitalized patients.

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Cel­lec­tis slammed af­ter pa­tient dies and FDA slaps a hold on their tri­al for an off-the-shelf CAR-T for mul­ti­ple myelo­ma

Cellectis was slammed after the market close on Monday as the biotech reported that the FDA demanded it hit the brakes on their MELANI-01 trial for their off-the-shelf cell therapy UCARTCS1A after one of the patients in the study died of treatment-related cardiac arrest.

The multiple myeloma patient had previously been treated unsuccessfully with various therapies, noted the biotech, and had been given dose level two (DL2) of their allogeneic CAR-T.

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Jean-Paul Clozel, Idorsia CEO (Patrick Straub/Keystone via AP Images)

Sec­ond PhI­II study for Idor­si­a's sleep drug re­turns pos­i­tive re­sults, but al­so rais­es new ques­tions

Following a successful Phase III study in April showcasing the safety and potential of its new sleep drug, Idorsia posted some mixed news in the second Phase III study, but that won’t stop a planned filing aimed at regulatory approval.

The drug, a dual orexin receptor antagonist (DORA) called daridorexant, was found to significantly improve sleep maintenance and subjective total sleep time in 25 mg doses, replicating results from the first Phase III study. However, improvements in sleep onset and daytime functioning narrowly missed statistical significance, despite numerical consistency with the April study.

UP­DAT­ED: Im­munomedics spells out PFS ben­e­fit of Trodelvy in mTNBC, hunt­ing a full OK just weeks af­ter ac­cel­er­at­ed ap­proval

By the time the FDA finally granted an accelerated OK for Immunomedics’ Trodelvy, we already got a very strong hint that their confirmatory Phase III study in metastatic triple-negative breast cancer was a success.

That’s because the independent data safety monitoring committee recommended that the trial be stopped early. But just what pointed them to the conclusion was still unclear.

“We do not know the totality of their decision other than it’s pretty evident that the primary endpoint was met; otherwise they could not request to halt the study,” Behzad Aghazadeh, the executive chairman, told Endpoints News at the time.

Shoshanna Shendelman, Applied Therapeutics CEO (Applied Therapeutics)

A lit­tle biotech slaps back at a 'crim­i­nal' short at­tack, vow­ing to pur­sue a pros­e­cu­tion of their case

As short attacks go, Biotech Research Partners’ assault on Applied Therapeutics’ “cherry picked” data and a variety of so-called red flags didn’t cause a whole lot of damage. Ahead of the July 4 holiday, its shares $APLT were dinged and showed signs of quick recovery.

But that didn’t stop an incendiary response, as the biotech swung into action bright and early Monday morning.

Applied Therapeutics accused the authors of the short report of manipulating graphs and figures, misrepresenting data and included factual misrepresentations — all of which added up, in their view, to fraud.

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

A boom­ing Drag­on­fly is tak­ing its TriN­KETs to Copen­hagen as the lat­est Bris­tol My­ers pact spurs ex­pan­sion plans — out­side the US

Bristol Myers Squibb is making a habit out of collaborating with the crew at Dragonfly, adding their 3rd deal in a series that now will take them into newly charted R&D territory. And the fast-growing team at the Cambridge-based biotech is adding a facility in Copenhagen for its next growth spurt, where the government is making it easy to recruit scientists internationally as the U.S. throttles back.

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Ernest Loumaye, ObsEva CEO (ObsEva)

UP­DAT­ED: Ob­sE­va’s sec­ond uter­ine fi­broids PhI­II comes through, send­ing some in­vestors to the hills

In the three-company race to develop a new uterine fibroid treatment, ObsEva long lagged behind AbbVie and Myovant. Still, they hoped that better efficacy — including a 93.9% response rate in one Phase III trial — could ultimately deliver better sales.

Now, though, the second of those Phase III studies is out, and it has brought the Swedish biotech back to earth.

In the second of their Phase III trials, 75.5% of patients who took ObsEva’s experimental tablet linzagolix plus a hormone saw their bleeding reduced by at least 50% and at least 80 ml after 24 weeks. Pooling those results with new data from their first Phase III trial — which showed a 93.9% response rate at 24 weeks and a 91.6% response rate at 52 weeks — ObsEva calculated a collective 84.7% responder rate for patients taking their therapy and said the data “confirm potential best-in-class” status.

Covid-19 roundup: Teamed up with NIH, Re­gen­eron launch­es PhI­II pre­ven­tion tri­al for an­ti­body cock­tail

As Regeneron moves its antibody cocktail into Phase II/III trials testing REGN-COV2 as a treatment for both hospitalized and non-hospitalized patients with Covid-19, the biotech is also starting a Phase III in the prevention setting.

The National Institute of Allergy and Infectious Diseases — which orchestrated the large, randomized study for remdesivir that produced positive results — will jointly run the study.

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Bel­lus hit with a set­back as its PhII chron­ic cough drug flops on all 4 dos­es -- shares cre­mat­ed on Wall Street

Bellus Health says their Phase II study for a new drug to treat chronic cough failed, but they already lined up Plan B to help ease the sting with investors.

The biotech tested 4 different doses of BLU-5937 in the mid-stage study, all of which fell short of the mark for placebo-adjusted reductions in coughing — several by a wide margin. It also didn’t help that there was no clear dose response in the mix, with a jumble of outcomes to report. Bellus $BLU immediately tried to shift focus to a silver lining, noting that they hit statistical significance among a subgroup of “high cough count patients (all patients at or above the baseline median average of 32.4 coughs per hour).”