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: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Stephen Hahn, AP

The FDA has de­val­ued the gold stan­dard on R&D. And that threat­ens every­one in drug de­vel­op­ment

Bioregnum Opinion Column by John Carroll

A few weeks ago, when Stephen Hahn was being lightly queried by Senators in his confirmation hearing as the new commissioner of the FDA, he made the usual vow to maintain the gold standard in drug development.

Neatly summarized, that standard requires the agency to sign off on clinical data — usually from two, well-controlled human studies — that prove a drug’s benefit outweighs any risks.

Over the last few years, biopharma has enjoyed an unprecedented loosening over just what it takes to clear that bar. Regulators are more willing to drop the second trial requirement ahead of an accelerated approval — particularly if they have an unmet medical need where patients are clamoring for a therapy.

That confirmatory trial the FDA demands can wait a few years. And most everyone in biopharma would tell you that’s the right thing for patients. They know its a tonic for everyone in the industry faced with pushing a drug through clinical development. And it’s helped inspire a global biotech boom.

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UP­DAT­ED: New play­ers are jump­ing in­to the scram­ble to de­vel­op a vac­cine as pan­dem­ic pan­ic spreads fast

When the CNN news crew in Wuhan caught wind of the Chinese government’s plan to quarantine the city of 11 million people, they made a run for one of the last trains out — their Atlanta colleagues urging them on. On the way to the train station, they were forced to skirt the local seafood market, where the coronavirus at the heart of a brewing outbreak may have taken root.

And they breathlessly reported every moment of the early morning dash.

In shuttering the city, triggering an exodus of masked residents who caught wind of the quarantine ahead of time, China signaled that they were prepared to take extreme actions to stop the spread of a virus that has claimed 17 lives, sickened many more and panicked people around the globe.

CNN helped illustrate how hard all that can be.

The early reaction in the biotech industry has been classic, with small-cap companies scrambling to headline efforts to step in fast. But there are also new players in the field with new tech that has been introduced since the last of a series of pandemic panics that could change the usual storylines. And they’re volunteering for a crash course in speeding up vaccine development — a field where overnight solutions have been impossible to prove.

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Mer­ck KGaA spin­out gets first fund­ing to bring dual-act­ing can­cer mol­e­cules in­to the clin­ic

Two and a half years after launch, Merck KGaA spinout iOnctura is getting its first major round of funding.

The oncology startup raised €15 million ($16.6 million) to put its lead drug into the clinic and get its second drug past IND-enabling tests. INKEF Capital and VI Partners co-led the round and were joined by the biotech’s longtime backer M Ventures, an arm of Merck KGaA, and Schroder Adveq.

Eli Lil­ly’s $1.6B can­cer drug failed to spark even the slight­est pos­i­tive gain for pa­tients in its 1st PhI­II

Eli Lilly had high hopes for its pegylated IL-10 drug pegilodecakin when it bought Armo last year for $1.6 billion in cash. But after reporting a few months ago that it had failed a Phase III in pancreatic cancer, without the data, its likely value has plunged. And now we’re getting some exact data that underscore just how little positive effect it had.

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Am­gen aug­ments Asia foothold by tak­ing over Astel­las joint ven­ture in Japan

California-based Amgen, which does the bulk of its business in the United States, made its ambition to reinvigorate its growth prospects by expanding its presence in Asia clear at the sidelines of the JP Morgan healthcare conference in San Francisco earlier this month.

The Thousand Oaks-based company on Thursday executed its plan to dissolve the joint venture with Astellas — created in 2013 — to operate the unit independently in Japan. With its rapidly aging population, the region represents an appealing market for Amgen’s osteoporosis treatments Prolia and Evenity as well as a cholesterol-lowering injection Repatha.

Daphne Zohar (PureTech)

PureTech bags $200M from sale of Karuna shares — still siz­zling from promis­ing schiz­o­phre­nia da­ta

Cashing in on the exuberance around Karuna Therapeutics and its potential blockbuster CNS drug, PureTech has sold a chunk of the biotech’s shares to Goldman Sachs for $200 million.

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