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.)

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Pfiz­er's big block­buster Xel­janz flunks its post-mar­ket­ing safe­ty study, re­new­ing harsh ques­tions for JAK class

When the FDA approved Pfizer’s JAK inhibitor Xeljanz for rheumatoid arthritis in 2012, they slapped on a black box warning for a laundry list of adverse events and required the New York drugmaker to run a long-term safety study.

That study has since become a consistent headache for Pfizer and their blockbuster molecule. Last year, Pfizer dropped the entire high dose cohort after an independent monitoring board found more patients died in that group than in the low dose arm or a control arm of patients who received one of two TNF inhibitors, Enbrel or Humira.

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Top gene ther­a­py deals, M&A pacts in 2020 high­light an­oth­er big year in one of the hottest fields in bio­phar­ma

Chris Dokomajilar at DealForma has been crunching the numbers on gene therapy deals over the last 2 years and came away with a few key observations.

Both the upfront cash and deal totals last year backed off a bit from the record high hit in 2019, but the totals are still running well ahead of anything we’ve seen in the years prior to 2019/2020.
2020 R&D partnerships came in at 23 deals, with $1.1 billion in disclosed upfront cash and equity and more than $8.5 billion in total deal value. Looking at 2019-2020 M&A, Dokomajilar found: 9 Acquisitions, with over $11.1 billion in disclosed upfront cash and equity and more than $13.4 billion in total M&A value.

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Steve Harr (L) and Hans Bishop

One of the most am­bi­tious start­up teams in biotech just out­lined plans for a $400M IPO and a val­u­a­tion of about $4B

The executive team at Sana Biotechnology has sketched out more details about the full scope of its ambitions as the new unicorn to watch. They amended their S-1 today to include a price range of $20 to $23 a share — which puts them in reach of pulling in around $400 million on the high end with a market value starting right around $4 billion.

That’s not bad for a preclinical biotech with no drugs yet in human studies, but it squares with its ambitions to remake the cell therapy field with a slate of in-house platforms. The biotech raised $705 million — primarily from ARCH (44 million shares) and Flagship (34.2 million shares) — to get to this stage.

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Bob Nelsen (Michael Kovac/Getty Images)

ARCH an­nounces largest fund yet, rais­ing $1.85B to back men­tal health, cell and gene edit­ing ap­proach­es

Nearly a year ago, as the pandemic encroached and the stock market cratered, Flagship and ARCH Venture announced three mega-funds worth a combined $2.6 billion. They wanted, ARCH’s Bob Nelsen said, to restore confidence “that there was money out there and a lot of it” to invest in biotech.

Since then, the stock market has returned — almost frighteningly so — and Nelsen has kept raising and spending cash. On Thursday, he announced a new fund, worth $1.85 billion. It’s the largest pot yet for a VC famous for its deep pockets.

Ther­mo Fish­er plat­form seeks to ex­pe­dite donor cell cul­ti­va­tion for al­lo­gene­ic cell ther­a­pies

One of the world’s leading CDMOs has launched a new technology it says will expedite a quickly-growing sect of biotech drug development: off-the-shelf, allogeneic cell therapies.

It’s been nearly a decade since the FDA approved the first use of the method that uses healthy donor cells to create a master cell bank, which is then used for specific therapies — a cord blood allogeneic treatment called Hemacord. In the years since, the use of allogeneic cells has taken off in research circles, most notably in the use of T cell therapies to target solid tumor cancers.

Take­da earns win for its TKI in­hibitor in tiny lung can­cer group — but GI side ef­fects could be an ear­ly red flag

Japanese drugmaker Takeda has made a big push in recent years to build a hand in oncology, particularly in the next-gen cancer space. One of those candidates, tyrosine kinase inhibitor (TKI) mobocertinib, recently earned the FDA’s interest in a small section of untreated lung cancer patients, but will severe GI side effects be a roadblock?

Takeda’s oral mobocertinib posted clinically significant objective response rates in a Phase I/II adaptive trial drugging metastatic non-small cell lung cancer patients with EGFR exon 20 gene mutations who had previously undergone platinum-based chemotherapy, according to data presented Thursday at the virtual World Conference on Lung Cancer.

Covid-19 roundup: EU and As­traZeneca trade blows over slow­downs; Un­usu­al unions pop up to test an­ti­bod­ies, vac­cines

After coming under fire for manufacturing delays last week, AstraZeneca’s feud with the European Union has spilled into the open.

The bloc accused the pharma giant on Wednesday of pulling out of a meeting to discuss cuts to its vaccine supplies, the AP reported. AstraZeneca denied the reports, saying it still planned on attending the discussion.

Early Wednesday, an EU Commission spokeswoman said that “the representative of AstraZeneca had announced this morning, had informed us this morning that their participation is not confirmed, is not happening.” But an AstraZeneca spokesperson later called the reports “not accurate.”

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Vas Narasimhan (AP Images)

BeiGene's PD-1 scores PhI­II win in esophageal can­cer — a 'key in­di­ca­tion' tapped by No­var­tis in $650M deal

Days after bringing BeiGene’s PD-1 into its portfolio, Novartis is adding a feather to its tislelizumab cap.

BeiGene reported that in the second-line setting, the checkpoint inhibitor extended overall survival for patients with esophageal squamous cell carcinoma, a key indication identified by Novartis. It was the primary endpoint in this Phase III trial.

“This is our fourth positive Phase 3 readout for tislelizumab and the first from our large Phase 3 program in gastrointestinal cancers that also include liver, stomach cancers as well as esophageal cancer,” BeiGene’s CMO in immuno-oncology, Yong Ben, said in a statement.

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