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.)

Com­mu­ni­cat­ing the val­ue of pre­ci­sion med­i­cine

By Natasha Cowan, Content Marketing Manager at Blue Latitude Health.
Many stakeholders are confused by novel precision medicines, including patients and healthcare professionals. So, how can industry help them to navigate this complexity?

Precision medicine represents a new paradigm in healthcare. It embodies the shift from treating many patients with the same therapy, to having the tools to identify the best treatment for every patient.

Spe­cial re­port: Twen­ty ex­tra­or­di­nary women in bio­phar­ma R&D who worked their way to the top

What differentiates a woman leader in biopharma R&D from a man?

Not much, except there are fewer of them in senior posts. Data suggest women are not more risk-averse, family-oriented or less confident than their male counterparts — indeed the differences between the two sexes are negligible. But a glance at the top R&D positions in Big Pharma leaves little doubt that upward migration in the executive ranks of biopharma R&D is tough.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 64,800+ biopharma pros reading Endpoints daily — and it's free.

The lat­est Cin­derel­la sto­ry in on­col­o­gy ends with a sud­den rout as up­dat­ed da­ta dis­play spooks in­vestors

NextCure’s turn as the Cinderella of cancer-focused biotechs was short-lived.
Just a few days after its shares $NXTC zoomed up more than 250% on some very early stage results in a SITC abstract, a more complete analysis over the weekend spiked the hype and left investors in high dudgeon as the stock price collapsed back towards earth Monday.
The focus at NextCure is centered on NC318, an antibody that is intended to shut down the immunosuppressive Siglec-15 — or S-15 — target. After adding a small group of patients to the readout, investigators circled 2 clinical responses, a complete and partial response, along with 4 stable disease cases in non-small cell lung cancer.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 64,800+ biopharma pros reading Endpoints daily — and it's free.

Te­va spin­out rais­es $85M in IPO; No­var­tis beefs up gener­ics unit with $440M deal

→ After Teva spinout 89bio recently announced that its IPO was being held up, the company is back in the game offering 5,304,687 shares at a price of $16 per share. The company has raised $84.9 million IPO in gross proceeds and will be listed under the ticker symbol $ETNB. BofA Securities, SVB Leerink and RBC Capital Markets are the joint book-running managers for the offering. Oppenheimer & Co is the co-manager for the offering.
→ Looking to amp up its presence in Japan’s hospitals, Novartis has struck a deal to buy out Aspen’s portfolio of generics in the world’s third largest healthcare market. The pharma giant is paying $440 million for Aspen’s Japanese subsidiary.
→ Novartis said tropifexor, a non-bile acid FXR agonist, has scored on several key biomarkers of NASH in a Phase IIb trial, including reductions in hepatic fat, alanine aminotransferase and body weight compared to a placebo at 12 weeks.

Break­through sta­tus and promise of a speedy re­view ar­rives for Op­di­vo/Yer­voy com­bi­na­tion as Bris­tol-My­ers bites at Bay­er

Its frontline and single-agent aspirations have been set back, but Bristol-Myers Squibb just took a big step forward in its efforts to apply its checkpoint inhibitor Opdivo to liver cancer. The FDA has granted breakthrough status and priority review to a combination, second-line treatment.

The designation is for Opdivo (nivolumab) in combination with Yervoy (ipilimumab),  for treating advanced hepatocellular carcinoma (HCC), the most common form of liver cancer. The PD-L1 drug was already approved as a single-agent, second-line treatment for HCC. A PDUFA date was set for March 10, 2020 — just 4 months from now.

Third time un­lucky: Lipocine's lat­est quest to mar­ket their oral testos­terone drug snubbed again by FDA

Lipocine’s latest attempt at securing approval for its oral testosterone drug has fizzled yet again.

The Utah-based drug developer on Monday said the FDA has spurned its marketing application, indicating that some efficacy data on the drug, Tlando, was not up to scratch to treat male hypogonadism, a condition characterized by low production of the hormone testosterone, which is responsible for maintaining muscle bulk, bone growth, and sexual function.

UP­DAT­ED: De­cry­ing 'ar­bi­trary and capri­cious' ac­tion, Re­genxBio sues FDA over clin­i­cal holds on gene ther­a­py

When RegenxBio disclosed that the FDA had placed a partial clinical hold on one of its lead gene therapies, execs outlined several customary next steps: continuing assessment and monitoring, delaying a related IND filing, and working with the FDA to address the matter.

As it turned out, they were planning something much less mundane. Two days after announcing the hold in its Q3 update, RegenxBio filed a lawsuit seeking to set it aside, the FDA Law Blog noted.

Roche's SMA chal­lenge to Bio­gen's Spin­raza fran­chise looms larg­er with piv­otal win

Roche has just landed a crucial advance in scoring a come-from-behind win on the spinal muscular atrophy field, giving Novartis and Biogen a run for their money.

The update was brief, but Roche said risdiplam hit the primary endpoint in the placebo-controlled pivotal SUNFISH trial, meeting the threshold for change from baseline in the Motor Function Measure 32 (MFM-32) scale after one year of treatment. The results, which is the second, confirmatory portion of a two-part study, involved 180 patients with type 2 or 3 spinal muscular atrophy between 2 and 25 years old.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 64,800+ biopharma pros reading Endpoints daily — and it's free.

Roche steers Gazy­va in­to a new PhI­II pro­gram af­ter com­bo shows promise in lu­pus nephri­tis study

Roche is working on putting together a late-stage study for its monoclonal antibody Gazyva in patients with severe kidney disease associated with lupus after a combination approach helped patients in a mid-stage study.

The 125-patient NOBILITY trial evaluated Gazyva, combined with standard-of-care treatment mycophenolate mofetil or mycophenolic acid and corticosteroids, versus standard treatment alone. The combo met the main goal of inducing a statistically superior complete renal response (CRR) of 40% at week 76, versus 18% in patients given standard treatment, Roche said.