Just how con­fi­dent is Arie Bellde­grun about Kite's po­si­tion in the tur­bu­lent CAR-T race? He's glad you asked.

Ear­ly on in his ca­reer, Arie Bellde­grun did re­search un­der Steven Rosen­berg at the NCI. Now, look­ing back over the in­ter­ven­ing decades, he still mar­vels at the first ground­break­ing lab ex­per­i­ments that would even­tu­al­ly point to the late-stage CAR-T ther­a­pies at a hand­ful of com­pa­nies like Kite Phar­ma, where he’s the CEO now and Rosen­berg is the em­i­nent sci­en­tist in his cor­ner of the ring.

“We were so im­pressed that T cells were killing can­cer cells in vi­vo, in 1985,” Bellde­grun tells me. “That’s where it start­ed. Since then we’ve con­tin­ued to work.”

Lat­er, much lat­er, en­gi­neer­ing T cells with the right anti­gen would pro­duce dra­mat­ic re­sults in pa­tients who had run out of op­tions.  “That is 10 years old,” Bellde­grun says, “you can’t take it out of con­text.”

But you might be for­giv­en for it if you just tuned in over the last two years. The field has ex­plod­ed, at­tract­ing hun­dreds of mil­lions of dol­lars and the fixed at­ten­tion of some of the most in­ter­est­ing com­pa­nies in biotech.

Over just the last few months, the com­pet­i­tive line­up on CAR-T has changed dra­mat­i­cal­ly as the three lead­ing com­pa­nies turned in­to the fi­nal stretch in the race to see who will be the first on the mar­ket. Juno Ther­a­peu­tics was tripped by a brief clin­i­cal hold in Ju­ly fol­low­ing the death of four pa­tients, which pushed back its first po­ten­tial ap­proval to 2018. Then, just days ago, No­var­tis made the stun­ning an­nounce­ment that it is dis­band­ing its 400-mem­ber cell ther­a­py unit, lay­ing off 120 and ab­sorb­ing the sur­vivors in­to its on­col­o­gy di­vi­sion — a clear re­treat that left the phar­ma gi­ant look­ing frag­ile on the CAR-T front as it protest­ed that noth­ing had changed.

On­ly Kite has re­mained un­dam­aged and on track, still plug­ging away at long-stand­ing plans to launch mar­ket­ing in a loom­ing 2017. If any­thing, it picked up the pace, sur­pris­ing an­a­lysts with its re­cent­ly an­nounced de­ci­sion to piv­ot to the FDA in just a few weeks with the first round of da­ta from its first piv­otal study. And the com­pa­ny, which now has 350 staffers, plans to see that num­ber swell to 500 by the end of this year as it marks a big tran­si­tion in­to mar­ket­ing.

For Bellde­grun, though, this sprint to the fin­ish — as well as prep­ping for every­thing still ahead — is be­ing pro­pelled by the mo­men­tum of those decades of re­search work. In an in­ter­view with End­points News this week, he ad­mits to be­ing sur­prised by some re­cent events, and not so star­tled by oth­ers.

“I have the high­est re­spect for No­var­tis,” he adds, cit­ing David Ep­stein, the phar­ma chief who re­cent­ly was un­ex­pect­ed­ly bounced from the phar­ma gi­ant and who helped shep­herd the pro­gram, and CEO Joe Jimenez, who adopt­ed cell ther­a­pies as the next big thing in on­col­o­gy. “I wish them luck. I know what we are do­ing at Kite. It has ab­solute­ly no ef­fect on what we are do­ing.”

He does won­der, though, how you can man­age a op­er­a­tion like CAR-T re­quires in the midst of a ma­jor phar­ma R&D di­vi­sion, as No­var­tis is now plan­ning.

“This is where biotech­nol­o­gy is bet­ter than large phar­ma,” he says. CAR-T, he adds, isn’t about de­vel­op­ing a treat­ment in a vial or a pill, it’s a 24/7 process in­volv­ing mul­ti­ple peo­ple.

“How can No­var­tis be suc­cess­ful in­clud­ing cell ther­a­py in­to a phar­ma­co­log­i­cal group?” asks the Kite CEO. “I don’t know.”

One no­table sur­prise came from Juno, which had to drop flu­dara­bine from its piv­otal study of JCAR015 fol­low­ing a se­ries of deaths. As Juno would care­ful­ly ex­plain at AS­CO, it’s the mix­ture of flu­dara­bine and cy­clophos­phamide — the cy/flu com­bo — that con­di­tions pa­tients for the best re­sponse, clear­ing the path for the cell ther­a­py to work. But they would drop flu­dara­bine from the key tri­al in or­der to per­suade the FDA that it was safe to con­tin­ue.

“We came to the con­clu­sion that a low-dose com­bi­na­tion of flu­dara­bine and cy­clophos­phamide, plus the num­ber of cells we test­ed,” was the right way to go, ex­plains Bellde­grun. “Since then we have not changed it and we are not plan­ning to.”

“We found the right dose, in­ter­me­di­ate.” Too much, he adds, and you get huge tox­i­c­i­ty. Too lit­tle, and there’s no ef­fect. “Now we know the num­ber of cells to give, what is the best chemo ab­la­tion need­ed to get the best ef­fect” and al­low cells to pro­lif­er­ate.

Juno it­self is like­ly to agree with that as­sess­ment. As I re­port­ed ear­li­er to­day, the com­pa­ny has been work­ing on its own recipe, hop­ing to achieve the kind of con­fi­dence that Bellde­grun has in Kite’s work.

“It def­i­nite­ly changed the com­pet­i­tive scene,” Bellde­grun says about events at Juno, “and I can­not say it made it hard­er.”

The CEO cites oth­er ad­van­tages as well. Kite won their break­through drug des­ig­na­tion at the FDA as a com­pa­ny, says the CEO, while No­var­tis (tied to the Uni­ver­si­ty of Penn­syl­va­nia) and Juno (al­lied with Memo­r­i­al Sloan Ket­ter­ing) would re­ly on their aca­d­e­m­ic li­aisons. He’s con­vinced that di­rect ex­po­sure gave his com­pa­ny valu­able ex­pe­ri­ence in de­ci­pher­ing the agency’s ex­pec­ta­tions for their work.

He al­so is bull­ish about Kite’s ini­tial work across all CD19-pos­i­tive cells, see­ing Juno and No­var­tis’ ini­tial ap­proach to ALL as too lim­it­ing. And he ex­pects the field to con­tin­ue to make dra­mat­ic leaps that will con­tin­ue to dis­rupt the com­pet­i­tive land­scape.

“This is just the be­gin­ning of a rev­o­lu­tion­ary tech­nol­o­gy,” he says. Syn­thet­ic bi­ol­o­gy will help give birth to su­per T cells that can go far be­yond where Kite or any­one else can ap­proach now. With gene edit­ing, he says, you can ed­it in a PD-L1 check­point in­hibitor, not give it to pa­tients sep­a­rate­ly.

Those fu­ture tech­nol­o­gy waves will give oth­er com­pa­nies a chance to step in, just as No­var­tis or some oth­er big play­ers may choose to buy in at the right time.

“Whether they push it now or not is ir­rel­e­vant,” says Bellde­grun, “they [No­var­tis] can come back lat­er, find an­oth­er com­pa­ny.”

In the mean­time, he’s al­so been work­ing with GE to make big im­prove­ments in the man­u­fac­tur­ing process, look­ing to trans­form what has been a very com­plex, time-con­sum­ing process in­to a quick, sim­ple turn­around that will be need­ed to help make this a com­mer­cial suc­cess.

Says Bellde­grun: “GE will rev­o­lu­tion­ize every­thing.”

And just as Kite was in on the be­gin­ning of the CAR-T rev­o­lu­tion, he ex­pects it to be a leader in what’s com­ing.

So far, he’s been right in a field where wrong turns have been plen­ti­ful. Steer­ing the com­pa­ny through the next phase will re­quire all the ex­pe­ri­ence that Bellde­grun likes to cite. It will al­so like­ly take some luck. The CEO doesn’t seem to lack for ei­ther right now.

Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology
ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development
CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

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Hal Barron. GSK

GSK's Hal Bar­ron her­alds their sec­ond pos­i­tive piv­otal for cru­cial an­ti-BC­MA ther­a­py, point­ing to a push for quick OKs in a crowd­ed field

Hal Barron has his second positive round of Phase III data in hand for his anti-BCMA antibody drug conjugate belantamab mafodotin (GSK2857916). And GSK’s research chief says the data paves the way for their drive in search of an FDA approval for treating multiple myeloma.

It’s hard to overestimate the importance of this drug for GSK, a cornerstone of Barron’s campaign to make a dramatic impact on the oncology market and provide some long-lost excitement for the pharma giant’s pipeline. They’re putting this BCMA program at the front of that charge — looking to lead a host of rivals all aimed at the same target.

We don’t know what the data are yet, but DREAMM-2 falls on the heels of a promising set of data delivered 5 months ago for DREAMM-1. There investigators noted that complete responses among treatment-resistant patients rose to 15% in the extra year’s worth of data to look over, with a median progression-free survival rate of 12 months, up from 7.9 months reported earlier. The median duration of response was 14.3 months.

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Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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Why would Am­gen want to buy Alex­ion? An­a­lysts call hot­ly ru­mored takeover un­like­ly, but seize the mo­ment

A rumor that Amgen is closing in on buyout deal for Alexion has sparked a guessing game on just what kind of M&A strategy Amgen is pursuing and how much Alexion is worth.

Mizuho analyst Salim Syed first lent credence to the report out of the Spanish news outlet Intereconomía, which said Amgen is bidding as much as $200 per share. While the source may be questionable, “the concept of this happening doesn’t sound too crazy to me,” he wrote.

FDA asks why No­var­tis took two months to launch for­mal in­ter­nal probe, af­ter AveX­is flagged da­ta ma­nip­u­la­tion

And the plot thickens. Novartis $NVS officials are reportedly now scrambling to explain to the FDA why it took them two months to open an internal investigation into data discrepancies for their $2.1 million gene-therapy for spinal muscular dystrophy — the world’s most expensive drug.

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Build­ing on suc­cess­ful PD-1 pact, Eli Lil­ly li­cens­es di­a­betes drug to Chi­nese part­ners at In­novent

Eli Lilly is expanding its partnership with China’s Innovent in a deal involving a diabetes drug sitting in its Phase I reserves.

The two companies had jointly developed one of China’s first homegrown PD-1 agents, scoring an approval for Tyvyt (sintilimab) late last year for relapsed/refractory classical Hodgkin’s lymphoma. This time around, Lilly is out-licensing a piece of its diabetes pipeline, a leading franchise that has historically produced the top-selling Trulicity and Humalog.

Am­gen, Al­ler­gan biosim­i­lar of Roche's block­buster Rit­ux­an clears an­oth­er US piv­otal study 

Novartis $NVS may have given up, but Amgen $AMGN and Allergan $AGN are plowing ahead with their knockoff of Roche’s blockbuster biologic Rituxan in the United States.

Their copycat, ABP 798, was found to have a clinically equivalent impact as Rituxan — meeting the main goal of the study involving CD20-positive B-cell non-Hodgkin’s lymphoma patients. This is the second trial supporting the profile of the biosimilar. In January, it came through with positive PK results in patients with rheumatoid arthritis.

Trump ad­min­is­tra­tion re­vives bid to get drug list prices on TV ads

The Trump administration is not giving up just yet. On Wednesday, the HHS filed an appeal against a judge’s decision in July to overturn a ruling obligating drug manufacturers to disclose the list price of their therapies in television adverts — hours before it was stipulated to go into effect.

In May, the HHS published a final ruling requiring drugmakers to divulge the wholesale acquisition cost— of a 30-day supply of the drug — in tv ads in a bid to enhance price transparency in the United States. The pharmaceutical industry has vehemently opposed the rule, asserting that list prices are not what a typical patient in the United States pays for treatment — that number is typically determined by the type of (or lack thereof) insurance coverage, deductibles and out-of-pocket costs. Although there is truth to that claim, the move was considered symbolic in the Trump administration’s healthcare agenda to hold drugmakers accountable in a climate where skyrocketing drug prices have incensed Americans on both sides of the aisle.