With one BLA at the FDA, Kite hus­tles along im­pres­sive new leukemia da­ta and sounds a note of cau­tion on safe­ty

CHICA­GO — With its lead pro­gram for non-Hodgkin lym­phoma in front of FDA re­view­ers, Kite Phar­ma $KITE to­day up­dat­ed their Phase I CAR-T study on re­lapsed cas­es of acute lym­phoblas­tic leukemia, not­ing a strik­ing­ly high com­plete re­mis­sion rate of 73% as they con­tin­ue to work on im­prov­ing the safe­ty pro­file of their ther­a­py.

The study in­clud­ed 11 pa­tients in the Phase I por­tion of ZU­MA-3. Com­plete re­mis­sions — with the re­spon­ders all test­ing neg­a­tive for min­i­mal resid­ual dis­ease with few or no can­cer cells in cir­cu­la­tion — were be­ing tracked that last­ed from 2 to more than 7.4 months. And the Phase II tri­al will get un­der­way as Kite looks to ex­pand use of its drug KTE-C19.

David Chang, Kite

“In many ways it sort of con­firms what we thought we’d see in the clin­i­cal study; very rapid re­sponse in 2 to 4 weeks,” Kite CMO David Chang tells me.

Safe­ty, though, re­mains a key con­cern. These CAR-T stud­ies have been marred from the be­gin­ning by com­mon cas­es of cy­tokine re­lease syn­drome. In this tri­al, there were three cas­es of grade three or high­er CRS with one death and six cas­es of grade three or high­er neu­ro­log­i­cal re­ac­tions.

That left Kite look­ing at who should re­ceive tocilizum­ab with­in 36 hours post‐KTE‐C19 in­fu­sion, and a low­er dose of 0.5×10(6) CAR T cells/kg rather than the two dos­es of 2.0×10(6)/kg and 1.0×10(6)/kg used in the first round.

Kite re­cent­ly re­port­ed that one pa­tient died re­cent­ly from cere­bral ede­ma, or brain swelling, in a sep­a­rate tri­al, rat­tling in­vestors who didn’t like the com­par­isons to the five cas­es of cere­bral ede­ma that forced Juno to scrap their led pro­gram, leav­ing Kite and No­var­tis alone in the race to a po­ten­tial first ap­proval lat­er this year.

Kite has learned a lot about con­trol­ling safe­ty, says Chang. Dos­ing, get­ting rid of in­fec­tions be­fore treat­ment, prepar­ing to bat­tle back CRS are all part of the game plan now.

Cas­es of cere­bral ede­ma have al­so sparked a de­bate over whether the CD28 cos­tim­u­la­to­ry do­main Kite us­es in their CAR-Ts — in­stead of the 4-1BB do­main No­var­tis us­es — could be re­spon­si­ble. Juno’s ini­tial lead ther­a­py al­so used the CD28 cos­tim­u­la­to­ry do­main.

“In a way I can see why some peo­ple would say that, but there’s re­al­ly no ba­sis to draw that con­clu­sion,” says Chang. He adds that there have been cas­es of cere­bral ede­ma with 4-1BB go­ing back to the ear­ly aca­d­e­m­ic stud­ies.

Chang al­so isn’t keen on mak­ing cross-tri­al com­par­isons.

“There’s a lot of false con­clu­sions that one can draw,” he says. But out­comes can be al­tered by the char­ac­ter­is­tics of the pa­tients re­cruit­ed, whether they were tru­ly chemo re­frac­to­ry or sim­ply re­lapsed, how many times they had re­lapsed on mul­ti­ple lines of ther­a­py and the dis­tri­b­u­tion of dis­ease types, all of which play in­to the da­ta.

Kite has al­so been hon­ing its man­u­fac­tur­ing skills. In this lat­est Phase I the man­u­fac­tur­ing team was able to get the time it takes to make the ther­a­py from pa­tient cells down to six days. Chang says that the com­pa­ny has the vein-to-vein time down to about 17 days, which he be­lieves can still like­ly be im­proved by two or three days.

Jean-Paul Clozel, Idorsia CEO (Patrick Straub/Keystone via AP Images)

Idor­si­a's brain bleed drug flunks PhI­II tri­al, a decade af­ter pre­vi­ous flop

Idorsia’s long journey with clazosentan came to an abrupt “unexpected result” Monday morning with a Phase III flop.

The Swiss biopharma said the drug did not meet the main goal of the late-stage REACT study, conducted in the US, Canada and Europe since early 2019.

The 409-patient trial tested the intravenous drug’s ability to prevent complications due to delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage (aSAH), in which blood vessels in the brain narrow and blood accumulates around the brain’s surface, which then dials up the pressure on the brain.

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Kenji Yasukawa, Astellas CEO (Photographer: Akio Kon/Bloomberg via Getty Images)

Astel­las taps chief strat­e­gy of­fi­cer as next CEO to 'go on the ag­gres­sive'

Five years into its big R&D revamp, Astellas says it’s time for a changing of the guard.

Kenji Yasukawa, who took over as president and CEO in 2018, will step down to become chairman of the board in April, making room for Naoki Okamura to take over. Okamura joined the company in 1986 and has served in a variety of finance, business and strategy roles, including most recently as chief strategy officer.

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Clin­i­cal tri­al di­ver­si­ty da­ta show mis­match be­tween en­roll­ment and dis­ease preva­lence, GSK says

A lack of diversity in clinical trials has persisted despite decades of initiatives to try to turn the tide.

In a recent review of 17 years of clinical trials, drugmaker GSK found that there were some mismatches between the demographics of its US-based trials and how prevalent diseases were in those populations.

The results, the company says, will help GSK and others design studies that better represent epidemiological rates within races and ethnicities.

The Big Phar­ma dis­card pile; Lay­offs all around while some biotechs bid farewell; New Roche CEO as­sem­bles top team; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

With earnings seasons in full swing, we’ve listened in on all the calls so you don’t have to. But news is popping up from all corners, so make sure you check out our other updates, too.

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Ma­gen­ta halts stem cell work and may sell it­self fol­low­ing pa­tient death, clin­i­cal hold

Magenta Therapeutics said it is halting work on its stem cell transplant drug pipeline and may sell itself, a week after the company reported the death of a patient in an early stage trial of its antibody-drug conjugate.

The Cambridge, MA-based company said it will conduct a “review of strategic alternatives,” and that could include an “acquisition, merger, business combination, or other transaction.”

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How to use ex­ter­nal con­trols: FDA spells out think­ing in new draft guid­ance

The use of real-world evidence to inform the FDA’s decision-making continues apace, with the agency releasing new draft guidance yesterday on how sponsors can compare outcomes of trial participants receiving a test treatment with outcomes in a group of people external to the trial.

The practice of externally controlled trials is common, particularly in oncology or other difficult areas where it’s not ethical or feasible to use internal controls.

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The Big Phar­ma axe: Mer­ck cuts chikun­gun­ya vax, Bris­tol My­ers drops Cy­tomX-part­nered pro­gram, and more

As fourth quarter earnings come in, Big Pharmas are disclosing changes to their pipelines during their investor calls, and sometimes more quietly in presentation appendices.

Merck dropped its chikungunya vaccine candidate, which completed a Phase II study. Merck acquired the vaccine through its purchase of Themis Bioscience in 2020. In developing a vaccine for chikungunya, a mosquito-borne virus, Valneva is the frontrunner, as it submitted its vaccine to the FDA at the end of December.

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Goldfinch Bio CEO Tony Johnson (L) and Karuna Therapeutics CEO Bill Meury

Karuna li­cens­es Goldfinch as­sets to com­pete with Boehringer In­gel­heim in neu­ro­science

Karuna Therapeutics is looking to compete with Boehringer Ingelheim on depression and anxiety with a new license to Goldfinch Bio’s assets, starting with $15 million to the shuttered biotech.

Karuna steps into an arena already being tested by Boehringer in multiple Phase II studies — the two are targeting transient receptor potential canonical 4 and 5, or TRPC4/5, which is thought to have a role in neuroscience indications. Goldfinch’s asset went through a Phase II in kidney diseases, but Karuna’s sights are set on mood and anxiety disorders for now.

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Roche's headquarters in Basel, Switzerland (Kyle LaHucik for Endpoints News)

Roche ditch­es fi­nal PhI­II for can­cer hope­ful, re­ports set­back for key drug in $1.4B buy­out

Over the past few years, Roche has released news about its AKT inhibitor ipatasertib in drips — most of them negative. The drug yielded mixed data in a key prostate cancer trial, Phase III flops in triple-negative breast cancer forced the pharma giant to pull the plug there, and in mid-2022 Roche trimmed two more early-stage indications in prostate cancer after completing the trials.

Now, the last piece of the program is gone.

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