Frank Neumann, Kite global head of clinical development

ASH: Gilead­'s CAR-T Yescar­ta holds up in more first-line lym­phoma pa­tients as part of ear­li­er use push

With the cell ther­a­py field large­ly piv­ot­ing to the next gen­er­a­tion of those drugs, es­tab­lished play­ers like Gilead’s Kite and Bris­tol My­ers Squibb are still carv­ing away at new routes in­to ear­li­er lines of care. This week­end, Kite churned out more da­ta for its CAR-T Yescar­ta in first-line lym­phoma pa­tients as part of a hope­ful push for a greater mar­ket share.

In up­dat­ed re­sults from the Phase II ZU­MA-12 study, Yescar­ta post­ed a 78% com­plete re­sponse rate among 37 pa­tients with high-risk large B cell lym­phoma at a me­di­an fol­low-up of just shy of 16 months, the drug­mak­ers said Mon­day at #ASH21.

These sin­gle-arm, open-la­bel da­ta fol­low re­sults pre­sent­ed at last year’s ASH show­ing a 73% com­plete re­sponse rate in 27 pa­tients and of­fer some proof of Yescar­ta’s last­ing dura­bil­i­ty in high-risk LB­CL pa­tients, most of whom even­tu­al­ly re­lapse af­ter first-line stan­dard of care, Kite said.

All me­di­an sur­vival check­points hadn’t been reached at a me­di­an 15.9 months af­ter in­fu­sion, but Kite float­ed 12-month out­comes es­ti­mates of 81% for durable re­spon­ders, 73% for event-free sur­vival, 75% for pro­gres­sion-free sur­vival and 91% for pa­tients still alive.

ZU­MA-12 is part of Gilead’s push in­to ear­li­er lines of ther­a­py for Yescar­ta be­yond its cur­rent ap­provals in third-line-or-lat­er blood can­cer. Al­so this week, Kite read out more da­ta from the Phase III ZU­MA-7 study show­ing Yescar­ta sig­nif­i­cant­ly beat out stan­dard-of-care in sec­ond-line LB­CL pa­tients as part of a head-to-head chal­lenge there.

Ac­cord­ing to Frank Neu­mann, Kite’s glob­al head of clin­i­cal de­vel­op­ment, Yescar­ta’s promis­ing ef­fi­ca­cy in first-line pa­tients could prove at­trac­tive to physi­cians look­ing for bet­ter op­tions than the chemother­a­py reg­i­men R-CHOP, the long­time stan­dard of this care in this set­ting that some pa­tients ei­ther can­not tol­er­ate or does not stop re­lapse in many pa­tients.

This study en­rolled a group of pa­tients Kite de­fined as high-risk with a rare ge­net­ic arrange­ment known as dou­ble- or triple-hit lym­phoma with a high prog­nos­tic score on a com­mon­ly used met­ric known as IPI, as well as a pos­i­tive PET fol­low­ing two cy­cles of treat­ment with a CD20-tar­get­ed an­ti­body and an­thra­cy­cline reg­i­men. Pa­tients were el­i­gi­ble for bridg­ing chemother­a­py be­fore their one-time in­fu­sion.

With the rise of ge­net­ic bio­mark­er test­ing, com­pa­nies are get­ting a bet­ter look ear­li­er at which pa­tients might be at high­er risk of re­lapse and thus in greater need of ear­ly in­ter­ven­tion from non-con­ven­tion­al ther­a­pies. In Kite’s case, that high-risk group is evolv­ing as ear­ly test­ing evolves, but Neu­mann said the com­pa­ny’s work in late-line pa­tients of­fers a pret­ty clear path for­ward in at least that one spe­cif­ic stan­dard for pa­tients.

“This field is evolv­ing — if you look at the mul­ti­ple myelo­ma space (for ex­am­ple), if you ask two physi­cians on ei­ther side of the At­lantic what a high-risk pa­tient is, you’ll get two dif­fer­ent re­spons­es,” Neu­mann said. “We have the tremen­dous ad­van­tage of hav­ing treat­ed so many pa­tients, and their clin­i­cal course and their trans­la­tion­al bio­mark­er da­ta is some­thing that we can lever­age and that we are learn­ing from, and that de­fines the ap­proach that the med­ical field thinks is a high-risk pop­u­la­tion.”

The big ques­tion in tak­ing cur­rent-gen­er­a­tion cell ther­a­pies in­to ear­li­er lines of care is a well-es­tab­lished safe­ty pro­file that in­cludes high risk of cy­tokine re­lease syn­drome and neu­ro­log­i­cal tox­i­c­i­ty. In this study, Grade 3 or high­er CRS oc­curred in 8% of pa­tients and 23% of pa­tients ex­pe­ri­enced a Grade 3 or high­er neu­ro­log­i­cal event. There were no deaths tied to treat­ment with Yescar­ta al­though one pa­tient died from Covid-19. All but one CRS and neu­ro­log­i­cal events were re­solved through treat­ment by the da­ta cut­off.

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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Uğur Şahin, BioNTech CEO (Andreas Arnold/picture-alliance/dpa/AP Images)

BioN­Tech opens new plas­mid DNA man­u­fac­tur­ing fa­cil­i­ty in Ger­many

German mRNA player BioNTech opened the doors to a new manufacturing facility on Thursday, this one just about 75 miles north of its headquarters in Mainz, Germany.

BioNTech announced on Thursday that it has completed the construction of its first plasmid DNA manufacturing facility in Marburg, Germany. The facility will produce materials for mRNA-based vaccines and therapies along with cell therapies.

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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