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.

UP­DAT­ED: Clay Sie­gall’s $614M wa­ger on tu­ca­tinib pays off with solid­ly pos­i­tive piv­otal da­ta and a date with the FDA

Back at the beginning of 2018, Clay Siegall snagged a cancer drug called tucatinib with a $614 million cash deal to buy Cascadian. It paid off today with a solid set of mid-stage data for HER2 positive breast cancer that will in turn serve as the pivotal win Siegall needs to seek an accelerated approval in the push for a new triplet therapy.

And if all the cards keep falling in its favor, they’ll move from 1 drug on the market to 3 in 2020, which is shaping up as a landmark year as Seattle Genetics prepares for its 23rd anniversary on July 15.

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J&J's block­buster Ste­lara wins US ap­proval for ul­cer­a­tive col­i­tis

J&J’s Stelara, which is set to be in the top ten list of blockbusters come 2025, is now cleared by the FDA for use in ulcerative colitis (UC), an inflammatory disease of the large intestine.

The biologic targets interleukin (IL)-12 and IL-23 cytokines, which are known to play a key role in inflammatory and immune responses. Stelara, which generated about $4.7 billion in the first nine months of 2019, is a key player in the crowded marketplace of drugs to treat autoimmune disorders such as psoriasis, rheumatoid arthritis and Crohn’s disease. AbbVie’s star therapy, Humira, continues to dominate, despite its looming patent cliff in the United States, while others including J&J’s $JNJ own anti-IL23 Tremfya, Lilly’s $LLY anti-IL-17 Taltz and AbbVie’s $ABBV recently approved anti-IL-23 antibody Skyrizi carve out a slice of market share.

Drug com­pa­nies reach $260M set­tle­ment just ahead of opi­oid tri­al; Oys­ter Point set terms for $85M IPO

→ Hours before the first federal opioid trial was set to begin, three drug distributors and an opioid manufacturer agreed to a $260 million agreement settlement, the Wall Street Journal was the first to report. The deal — which will see McKesson, Cardinal Health and AmerisourceBergen pay $215 million to Summit and Cuyahoga counties, and Teva deal out $35 million in cash and addiction treatments — does not resolve the pending, nationwide litigation that may result in a settlement worth upwards of $40 billion. Negotiators in that case, brought by 2,300 tribes, counties and cities nationwide and led by several states’ attorneys general, worked through much of Friday without success. Josh Stein, the attorney general for North Carolina, said they were trying to put together a $48 billion deal.

GSK of­floads two vac­cines in $1.1B deal as it works to re­vive the pipeline

GlaxoSmithKline is leaving the deep dark woods and its viruses behind.

GSK has agreed to divest its vaccines for rabies, RabAvert, and tick-born encephalitis vaccine, Encepur, to Bavarian Nordic, part of the company’s broader efforts to narrow its pipeline and focus on oncology and immunology.

The deal is worth up to nearly $1.1 billion, with a $336 million upfront payment. GSK acquired the vaccines from Novartis as part of an exchange for their late-stage oncology programs in 2015 under former chief Sir Andrew Witty.

IM­brave150: Roche’s reg­u­la­to­ry crew plans a glob­al roll­out of Tecen­triq com­bo for liv­er can­cer as PhI­II scores a hit

Just weeks after Bristol-Myers Squibb defended its failed pivotal study pitting Opdivo against Nexavar in liver cancer, Roche says it’s beat the frontline challenge with a combination of their PD-L1 Tecentriq with Avastin. And now they’re rolling their regulatory teams in the US, Europe and China in search of a new approval — badly needed to boost a trailing franchise effort.
Given their breakthrough and Big Pharma status as well as the use of two approved drugs, FDA approval may well prove to be something of a formality. And the Chinese have been clear that they want new drugs for liver cancer, where lethal disease rates are particularly high.
Researchers at their big biotech sub, Genentech, say that the combo beat Bayer’s Nexavar on both progression-free survival as well as overall survival — the first advance in this field in more than a decade. We won’t get the breakdown in months of life gained, but it’s a big win for Roche, which has lagged far, far behind Keytruda and Opdivo, the dominant PD-1s that have captured the bulk of the checkpoint market so far.
Researchers recruited hepatocellular carcinoma — the most common form of liver cancer — patients for the IMbrave150 study who weren’t eligible for surgery ahead of any systemic treatment of the disease.
Roche has a fairly low bar to beat, with modest survival benefit for Nexavar, approved for this indication 12 years ago. But they also plan to offer a combo therapy that could have significantly less toxicity, offering patients a much easier treatment regimen.
Cowen’s Steven Scala recently sized up the importance of IMbrave150, noting:

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Pfiz­er gets some en­cour­ag­ing PhI­II news on a fran­chise sav­ior, but is a dos­ing ad­van­tage worth the $295M up­front?

Close to 3 years after Opko tried to defend itself as shares tumbled on the news that its long-acting growth hormone had failed to outperform a placebo, the Pfizer partner $PFE is back. And this time they’re pitching Phase III data that demonstrate their drug is non-inferior — or maybe a tad better — than their well-known but fading standard in the field.
The comparator drug here is Genotropin, which earned a marginal $142 million for Pfizer last year — down 9% from the year before. Approved 24 years ago, biosimilars are now in development that Pfizer would like to stay out in front of. The market leader here is Norditropin, a growth hormone from Novo Nordisk that uses the same basic ingredient as Genotropin, which the Danish company sells with a kid-friendly self-injectable pen. That would also present some big competition if the new therapy from Opko/Pfizer makes it to the market.
The new data, says researchers, underscore that a weekly injection of somatrogon performed as well or slightly better than Genotropin (somatropin) in young children with growth hormone deficiency. Investigators tracked height velocity at 10.12 cm/year, edging out the older drug’s 9.78 cm/year. That 0.33 difference may not prove compelling to payers, though, who have been known to overlook dosing advantages in favor of lower costs.
That message may have weighed on the stock reaction this morning, with a 30%-plus hike $OPK giving way to more marginal gains.
Back in late 2016, Opko had to defend itself against a devastating Phase III setback as their initial late-stage trial failed against a sugar pill. Opko later blamed that setback on outliers in the study, though it wasn’t able to expunge the failure.

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As­traZeneca's Farx­i­ga scores FDA nod to cut risk of hos­pi­tal­iza­tion for heart fail­ure in di­a­bet­ics

While the FDA recently spurned an application to allow AstraZeneca’s blockbuster drug Farxiga for type 1 diabetes that cannot be controlled by insulin, citing safety concerns — the US regulator has endorsed the use of the SGLT2 treatment to reduce the risk of hospitalisation for heart failure in patients with type-2 diabetes and established cardiovascular disease or multiple CV risk factors.

Sofinno­va-backed Abi­vax touts longer term mid-stage da­ta in ul­cer­a­tive col­i­tis

Two months after Abivax convinced Sofinnova to bankroll several mid-stage studies of its lead drug — ABX464 — with a €12 million stock purchase, the Paris-based biotech has rolled out more data on the anti-inflammatory molecule for all investors to see.

In a Phase IIa maintenance study involving 22 patients with moderate to severe ulcerative colitis who have been failed by previous treatments, 12 achieved clinical remission as assessed by endoscopy. But since only 19 completed the full one-year trial, 16 of whom had an endoscopy, investigators scored the remission rate at 75%. Although there’s no comparator arm, execs were pleased with improvements over an initial two-month, placebo-controlled induction phase by a number of measures ranging from remission to Mayo score and a fecal biomarker.

Alex­ion clinch­es aHUS ap­proval for Ul­tomiris as the clock ticks on Soliris con­ver­sion

Alexion has racked up a second approval for Ultomiris, the successor therapy to Soliris, as its mainstay blockbuster therapy faces a patent review process that could drastically shorten its patent exclusivity.

The FDA OK for atypical hemolytic uremic syndrome (aHUS) on Friday was widely expected after Alexion posted a full slate of positive Phase III data in January. But regulators also flagged concerns about serious meningococcal infections, slapping a black box warning on the label and mandating a REMS.