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.)

It’s fi­nal­ly over: Bio­gen, Ei­sai scrap big Alzheimer’s PhI­I­Is af­ter a pre­dictable BACE cat­a­stro­phe rais­es safe­ty fears

Months after analysts and investors called on Biogen and Eisai to scrap their BACE drug for Alzheimer’s and move on in the wake of a string of late-stage failures and rising safety fears, the partners have called it quits. And they said they were dropping the drug — elenbecestat — after the independent monitoring board raised concerns about…safety.

We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

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Deborah Dunsire. Lundbeck

Deb­o­rah Dun­sire is pay­ing $2B for a chance to leap di­rect­ly in­to a block­buster show­down with a few of the world's biggest phar­ma gi­ants

A year after taking the reins as CEO of Lundbeck, Deborah Dunsire is making a bold bid to beef up the Danish biotech’s portfolio of drugs in what will likely be a direct leap into an intense rivalry with a group of giants now carving up a growing market for new migraine drugs.

Bright and early European time the company announced that it will pay up to about $2 billion to buy Alder, a little biotech that is far along the path in developing a quarterly IV formulation for a CGRP drug aimed at cutting back the number of crippling migraines patients experience each month.

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Lisa M. DeAngelis, MSKCC

MSK picks brain can­cer ex­pert Lisa DeAn­ge­lis as its next CMO — fol­low­ing José Basel­ga’s con­tro­ver­sial ex­it

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His replacement, who now will be in charge of MSK’s cutting-edge research work as well as the cancer care delivered by hundreds of practitioners, is Lisa M. DeAngelis. DeAngelis had been chair of the neurology department and co-founder of MSK’s brain tumor center and was moved in to the acting CMO role in the wake of Baselga’s departure.

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After establishing itself as one of the pioneer research centers in the world for CAR-T cancer therapies, creating new attack vehicles to eradicate cancer cells, a team at Penn Medicine has begun the tricky transition of using the basic technology for heart repair work.

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Tal Zaks. Moderna

The mR­NA uni­corn Mod­er­na has more ear­ly-stage hu­man da­ta it wants to show off — reach­ing new peaks in prov­ing the po­ten­tial

The whole messenger RNA field has attracted billions of dollars in public and private investor cash gambled on the prospect of getting in on the ground floor. And this morning Boston-based Moderna, one of the leaders in the field, wants to show off a few more of the cards it has to play to prove to you that they’re really in the game.

The whole hand, of course, has yet to be dealt. And there’s no telling who gets to walk with a share of the pot. But any cards on display at this point — especially after being accused of keeping its deck under lock and key — will attract plenty of attention from some very wary, and wired, observers.

“In terms of the complexity and unmet need,” says Tal Zaks, the chief medical officer, “this is peak for what we’ve accomplished.”

Moderna has two Phase I studies it wants to talk about now.

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It's not per­fect, but it's a good start: FDA pan­elists large­ly en­dorse Aim­mune's peanut al­ler­gy ther­a­py

Two days after a fairly benign review from FDA staff, an independent panel of experts largely endorsed the efficacy and safety of Aimmune’s peanut allergy therapy, laying the groundwork for approval with a risk evaluation and mitigation strategy (REMS).

Traditionally, peanut allergies are managed by avoidance, but the threat of accidental exposure cannot be nullified. Some allergists have devised a way to dose patients off-label with peanut protein derived from supermarket products to wean them off their allergies. But the idea behind Aimmune’s product was to standardize the peanut protein, and track the process of desensitization — so when accidental exposure in the real world invariably occurs, patients are less likely to experience a life-threatening allergic reaction.

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More than two years ago Ritter Pharmaceuticals managed to find enough silver lining in its Phase IIb/III study — after missing the top-line mark — to propel its lactose intolerance toward a confirmatory trial. But as it turned out, the enthusiasm only set the biotech and its investors up to be sorely disappointed.

This time around there’s little left to salvage. Not only did RP-G28 fail to beat placebo in reducing lactose intolerance symptoms, patients in the treatment group actually averaged a smaller improvement. On a composite score measuring symptoms like abdominal pain, cramping, bloating and gas, patients given the drug had a mean reduction of 3.159 while the placebo cohort saw a 3.420 drop on average (one-sided p-value = 0.0106).

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Adverum, on Wednesday, unveiled 24-week data from the OPTIC trial of its experimental therapy, ADVM-022, in six patients who have been administered with one dose of the therapy. On average, patients in the trial had severe disease with an average of 6.2 anti-VEGF injections in the eight months prior to screening and an average annualized injection frequency of 9.3 injections.

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Too often, Alex Arfaei arrived too late. 

An analyst at BMO Capital Markets, he’d meet with biotech or pharmaceutical heads for their IPO or secondary funding and his brain, trained on a biology degree and six years at Merck and Endo, would spring with questions: Why this biomarker? Why this design? Why not this endpoint? Not that he could do anything about it. These execs were coming for clinical money; their decisions had been made and finalized long ago.