With one BLA at the FDA, Kite hus­tles along im­pres­sive new leukemia da­ta and sounds a note of cau­tion on safe­ty

CHICA­GO — With its lead pro­gram for non-Hodgkin lym­phoma in front of FDA re­view­ers, Kite Phar­ma $KITE to­day up­dat­ed their Phase I CAR-T study on re­lapsed cas­es of acute lym­phoblas­tic leukemia, not­ing a strik­ing­ly high com­plete re­mis­sion rate of 73% as they con­tin­ue to work on im­prov­ing the safe­ty pro­file of their ther­a­py.

The study in­clud­ed 11 pa­tients in the Phase I por­tion of ZU­MA-3. Com­plete re­mis­sions — with the re­spon­ders all test­ing neg­a­tive for min­i­mal resid­ual dis­ease with few or no can­cer cells in cir­cu­la­tion — were be­ing tracked that last­ed from 2 to more than 7.4 months. And the Phase II tri­al will get un­der­way as Kite looks to ex­pand use of its drug KTE-C19.

David Chang, Kite

“In many ways it sort of con­firms what we thought we’d see in the clin­i­cal study; very rapid re­sponse in 2 to 4 weeks,” Kite CMO David Chang tells me.

Safe­ty, though, re­mains a key con­cern. These CAR-T stud­ies have been marred from the be­gin­ning by com­mon cas­es of cy­tokine re­lease syn­drome. In this tri­al, there were three cas­es of grade three or high­er CRS with one death and six cas­es of grade three or high­er neu­ro­log­i­cal re­ac­tions.

That left Kite look­ing at who should re­ceive tocilizum­ab with­in 36 hours post‐KTE‐C19 in­fu­sion, and a low­er dose of 0.5×10(6) CAR T cells/kg rather than the two dos­es of 2.0×10(6)/kg and 1.0×10(6)/kg used in the first round.

Kite re­cent­ly re­port­ed that one pa­tient died re­cent­ly from cere­bral ede­ma, or brain swelling, in a sep­a­rate tri­al, rat­tling in­vestors who didn’t like the com­par­isons to the five cas­es of cere­bral ede­ma that forced Juno to scrap their led pro­gram, leav­ing Kite and No­var­tis alone in the race to a po­ten­tial first ap­proval lat­er this year.

Kite has learned a lot about con­trol­ling safe­ty, says Chang. Dos­ing, get­ting rid of in­fec­tions be­fore treat­ment, prepar­ing to bat­tle back CRS are all part of the game plan now.

Cas­es of cere­bral ede­ma have al­so sparked a de­bate over whether the CD28 cos­tim­u­la­to­ry do­main Kite us­es in their CAR-Ts — in­stead of the 4-1BB do­main No­var­tis us­es — could be re­spon­si­ble. Juno’s ini­tial lead ther­a­py al­so used the CD28 cos­tim­u­la­to­ry do­main.

“In a way I can see why some peo­ple would say that, but there’s re­al­ly no ba­sis to draw that con­clu­sion,” says Chang. He adds that there have been cas­es of cere­bral ede­ma with 4-1BB go­ing back to the ear­ly aca­d­e­m­ic stud­ies.

Chang al­so isn’t keen on mak­ing cross-tri­al com­par­isons.

“There’s a lot of false con­clu­sions that one can draw,” he says. But out­comes can be al­tered by the char­ac­ter­is­tics of the pa­tients re­cruit­ed, whether they were tru­ly chemo re­frac­to­ry or sim­ply re­lapsed, how many times they had re­lapsed on mul­ti­ple lines of ther­a­py and the dis­tri­b­u­tion of dis­ease types, all of which play in­to the da­ta.

Kite has al­so been hon­ing its man­u­fac­tur­ing skills. In this lat­est Phase I the man­u­fac­tur­ing team was able to get the time it takes to make the ther­a­py from pa­tient cells down to six days. Chang says that the com­pa­ny has the vein-to-vein time down to about 17 days, which he be­lieves can still like­ly be im­proved by two or three days.

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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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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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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UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

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Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll

As­traZeneca’s Imfinzi/treme com­bo strikes out — again — in lung can­cer. Is it time for last rites?

AstraZeneca bet big on the future of their PD-L1 Imfinzi combined with the experimental CTLA-4 drug tremelimumab. But once again it’s gone down to defeat in a major Phase III study — while adding damage to the theory involving targeting cancer with a high tumor mutational burden.

Early Wednesday the pharma giant announced that their NEPTUNE study had failed, with the combination unable to beat standard chemo at overall survival in high TMB cases of advanced non-small cell lung cancer. We won’t get hard data until later in the year, but the drumbeat of failures will call into question what — if any — future this combination can have left.

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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.