Kite’s ground­break­ing CAR-T hits key study goal, heads to the FDA

Kite Phar­ma is go­ing for it.

Now well out in front of its CAR-T ri­vals, Kite Phar­ma $KITE has gath­ered a promis­ing set of in­ter­im da­ta for KTE-C19 from the Phase II por­tion of its study for ag­gres­sive non-Hodgkin lym­phoma and will now set out to make its case with the FDA for an ac­cel­er­at­ed ap­proval.

The biotech says that 62 pa­tients in their study suf­fer­ing from sev­er­al types of NHL who com­plet­ed at least three months of treat­ment demon­strat­ed a com­bined com­plete re­sponse rate of 39%, down slight­ly from the Phase I da­ta. And six-month da­ta, which may be crit­i­cal in win­ning reg­u­la­tors over, is on its way.

Ac­cord­ing to Kite, KTE-C19 met the pri­ma­ry end­point with an ob­jec­tive re­sponse rate of 76% and 47% com­plete re­mis­sions. Kite’s shares jumped about 10% af­ter the da­ta hit.

There’s been no change in strat­e­gy, CEO Arie Bellde­grun tells me to­day. Their drug “is still in line for a 2017 ap­proval.”

A to­tal of 52 pa­tients with dif­fuse large B-cell lym­phoma (DL­B­CL) were stud­ied along­side 11 pa­tients with trans­formed fol­lic­u­lar lym­phoma (TFL) and pri­ma­ry me­di­asti­nal B-cell lym­phoma (PM­B­CL). And it has chart­ed pos­i­tive out­comes in all those groups, paving the way for Kite’s pi­o­neer­ing new drug ap­pli­ca­tion to the FDA.

To be sure, treat­ment-re­sis­tant pa­tients re­cruit­ed for the study al­so ex­pe­ri­enced sig­nif­i­cant ad­verse events. Two died — one from car­diac ar­rest and the oth­er for he­mo­phago­cyt­ic lym­pho­his­ti­o­cy­to­sis, which in­cludes a case of cy­tokine re­lease syn­drome — with high rates of  CRS, neu­trope­nia (66%), ane­mia (40%), febrile neu­trope­nia (29%), throm­bo­cy­tope­nia (29%) and en­cephalopa­thy.

But in­ves­ti­ga­tors say that they were not sur­prised by any of it, and nei­ther will any­one at the FDA.

“The sur­prise is that there is no sur­prise,” Bellde­grun added in an in­ter­view with me ear­li­er to­day. “The un­usu­al part is that ac­tu­al­ly the pro­file of tox­i­c­i­ty is bet­ter than what we re­port­ed in ZU­MA-1.”

The biotech plans to file by year’s end with the FDA, says the CEO. A pre-BLA meet­ing is sched­uled in the next few months, he adds, and reg­u­la­tors will have had a chance to re­view the da­ta pack­age in ad­vance. At that point, Kite plans to come up with a more pre­cise time­line.

The ad­verse events they record­ed are well known to the field and the agency, says the CEO. Based on SCHOL­AR-1 da­ta, these pa­tients would nor­mal­ly ex­pect to see an 8% com­plete re­sponse rate. Kite’s drug de­liv­ered a CR of 39%. In ad­di­tion, says Bellde­grun, Kite proved that it could man­u­fac­ture the per­son­al­ized ther­a­py for 22 cen­ters, most of which had nev­er han­dled the ther­a­py be­fore.

And 6-month and 9-month da­ta is on its way.

“The da­ta is com­ing,” says Kite R&D di­rec­tor David Chang. The pri­ma­ry analy­sis can be done in the first quar­ter, he adds, when in­ves­ti­ga­tors will have 6-month re­sponse times in place from the on­go­ing study. And Bellde­grun says that the com­pa­ny can pull the veil off the first one-year track records for some of its ear­li­est pa­tients at ES­MO, which is com­ing up ear­ly next month.

Con­vinc­ing the FDA that pre­lim­i­nary re­sponse du­ra­tions are long enough to war­rant a light­ning-fast ap­proval may prove to be Kite’s biggest chal­lenge. Over the last two years, though, top reg­u­la­tors like Richard Paz­dur have been quite will­ing to look past is­sues in­volv­ing safe­ty and ear­ly out­comes and go for the quick­est de­vel­op­ment path pos­si­ble, fre­quent­ly ap­prov­ing new ther­a­pies far short of any Phase III piv­otal test. But this is ag­gres­sive even by the agency’s most am­bi­tious time­lines.

Bellde­grun, how­ev­er, says that none of this is hap­pen­ing in a vac­u­um. Com­pa­ny ex­ecs and the FDA are in reg­u­lar con­tact and have more dis­cus­sions planned. And he be­lieves that once you add all the da­ta in from ear­li­er stud­ies, care­ful­ly weigh the case for ben­e­fits vs. safe­ty for a group of pa­tients who have run out of al­ter­na­tive ther­a­pies, a green light is com­plete­ly re­al­is­tic.

Kite’s move comes at the end of a tu­mul­tuous quar­ter for CAR-T, a field that spe­cial­izes in ex­tract­ing pa­tients T cells and reengi­neer­ing them in­to can­cer ther­a­pies. While there are a mul­ti­tude of ob­sta­cles for this first pi­o­neer­ing wave, the CAR-T ap­proach has worked best among these hema­to­log­ic pa­tients whose can­cer cells ex­press the CD19 tar­get. And reg­u­la­tors have bent over back­ward to speed their progress. The FDA, for ex­am­ple, im­posed a clin­i­cal hold on ri­val Juno’s lead CAR-T short­ly af­ter it trig­gered se­vere tox­i­c­i­ty and killed three pa­tients (a fourth died from cere­bral ede­ma in a sep­a­rate study).  But Juno was al­lowed to re­sume dos­ing in the lead tri­al just days lat­er, though, af­ter chang­ing the for­mu­la and drop­ping flu­dara­bine from the pre­con­di­tion­ing reg­i­men.

That small de­lay, though, wound up forc­ing Juno to for­feit the lead in its race with Kite. Juno is now look­ing at an ini­tial OK in 2018. No­var­tis, mean­while, stunned the field with its re­cent de­ci­sion to scrap its cell ther­a­py unit and lay off 120 staffers, news we broke at End­points. The phar­ma gi­ant in­sists it’s just as com­mit­ted as ever, but a num­ber of on­look­ers dis­count that as a like­ly PR gam­bit in­tend­ed to hide just how far the com­pa­ny has fall­en be­hind.

Kite, mean­while, is now at the FDA’s doors with a “break­through” des­ig­na­tion in hand and high hopes for a speedy ap­proval. If they’re right, you can look for a mar­ket launch ear­ly next year. If they made the wrong move, you’ll hear the noise at quite a dis­tance. And not every­one was en­thu­si­as­tic about the dura­bil­i­ty of the ther­a­py.

(Cor­rec­tion: This sto­ry was cor­rect­ed to re­flect that Juno’s lead drug killed three pa­tients, trig­ger­ing a brief clin­i­cal hold, while a fourth pa­tient in a sep­a­rate study died from cere­bral ede­ma.)

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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Hal Barron, Endpoints UKBIO20 (Jeff Rumans)

'Al­tos was re­al­ly a once-in-a-life­time op­por­tu­ni­ty': Hal Bar­ron re­flects on his big move

By all accounts, Hal Barron had one of the best jobs in Big Pharma R&D. He made more than $11 million in 2020, once again reaping more than his boss, Emma Walmsley, who always championed him at every opportunity. And he oversaw a global R&D effort that struck a variety of big-dollar deals for oncology, neurodegeneration and more.

Sure, the critics never let up about what they saw as a rather uninspiring late-stage pipeline, where the rubber hits the road in the Big Pharma world’s hunt for the next big near-term blockbuster, but the in-house reviews were stellar. And Barron was firmly focused on bringing up the success rate in clinical trials, holding out for the big rewards of moving the dial from an average 10% success rate to 20%.

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Executive Director of the EMA Emer Cooke (AP Photo/Geert Vanden Wijngaert)

Eu­ro­pean Par­lia­ment signs off on strength­en­ing drug reg­u­la­tor's abil­i­ty to tack­le short­ages

The European Parliament on Thursday endorsed a plan to increase the powers of the European Medicines Agency, which will be better equipped to monitor and mitigate shortages of drugs and medical devices.

By a vote of 655 to 31, parliament signed off on a provisional agreement reached with the European Council from last October, in which the EMA will create two shortage steering groups (one for drugs, the other for devices), a new European Shortages Monitoring Platform to facilitate data collection and increase transparency, and on funding for the work of the steering groups, task force, working parties and expert panels that are to be established.

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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Kenneth Galbraith, incoming Zymeworks CEO

Zymeworks re­places half its C-suite, aims to lay off 25% of to­tal work­force as new CEO takes over

New Zymeworks CEO Kenneth Galbraith is aiming to hit the ground running when his tenure officially begins next month, but he’ll be doing so with a much different looking team.

In a lengthy press release outlining the biotech’s 2022 goals, Galbraith said Zymeworks will be laying off at least 25% of its staff over the course of the year. Half of its C-suite will also be replaced immediately as Galbraith looks to remake the company in his image after Ali Tehrani, Zymeworks’ founder and CEO since 2003, stepped down two weeks ago.

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CBO: Medicare ne­go­ti­a­tions will ham­per drug de­vel­op­ment more than pre­vi­ous­ly thought

As President Biden’s Build Back Better Act — and, with it, potentially the Democrats’ last shot at major drug pricing reforms in the foreseeable future — remains on life support, the Congressional Budget Office isn’t helping their case.

The CBO last week released a new slide deck, outlining an update to its model on how Medicare negotiations might take a bite out of new drugs making it to market. The new model estimates a 10% long-term reduction in the number of new drugs, whereas a previous CBO report from August estimated that 8% fewer new drugs will enter the market over 30 years.