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.

UP­DAT­ED: In a fresh dis­ap­point­ment, Am­gen spot­lights a ma­jor safe­ty is­sue with KRAS com­bo

Amgen had hoped that its latest study matching its landmark KRAS G12C drug Lumakras with checkpoint inhibitors would open up its treatment horizons and expand its commercial potential. Instead, the combo spurred safety issues that blunted efficacy and forced the pharma giant to alter course on its treatment strategy, once again disappointing analysts who have been tracking the drug’s faltering sales and limited therapeutic reach.

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Ad­dress­ing the ‘Ca­pac­i­ty Crunch’ with a Scal­able Plat­form Process Ap­proach

The field of gene therapy has been diligently moving forward over the past several decades to bring potentially life-saving treatments to patients with genetic diseases. In addition to two approved adeno-associated viral (AAV) gene therapies, there are more than 250 AAV gene therapies in various clinical trial stages.1 AAV vectors remain the most frequently used vector for delivering therapeutic transgenes to target tissues due to their demonstrated and lasting clinical efficacy and extensive safety track record. As AAV therapies advance through clinical trials and into commercialization, many biotech companies are turning to contract development and manufacturing organizations (CDMOs) to prepare their programs for late-stage clinical and commercial scale manufacturing. Given the scope and scale of the manufacturing needs that will accompany regulatory approvals for these assets, CDMOs continue to expand their capacity to meet the needs of increasing prevalent patient populations. However, despite rapid growth, projected gene therapy manufacturing demands still outpace the collective capacity of the CDMO industry.

A $5B Pfiz­er buy­out? Am­gen, Gilead head­line M&A Thurs­day; Al­ny­lam's AT­TR sweep; An­drew Lo's rare dis­ease quest; 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.

One of the cool things about adding EndpointsPharma to the daily roster is that my colleagues can now dedicate time to tracking quarterly updates and tuning into calls with Big Pharma companies. Check out their dispatch from the Q2 earnings below.

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Bob Bradway, Amgen CEO (Justin Kase Conder/AP Images for Amgen)

UP­DAT­ED: Am­gen chief Brad­way nabs a rare dis­ease play­er in $4B buy­out as the M&A tem­po ac­cel­er­ates

Amgen CEO Bob Bradway is bellying up to the M&A table today, scooping up the newly anointed commercial biotech ChemoCentryx $CCXI and its recently approved rare disease drug for $3.7 billion out of the cash stockpile. The deal comes in at $52 a share — a hefty increase over the $24.11 close yesterday.

Bradway and the Amgen team get a drug called Tavneos (avacopan) in the deal, a complement factor C5a inhibitor OK’d to treat anti-neutrophil cytoplasmic autoantibody (ANCA)-vasculitis, an autoimmune disease which can be lethal.

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Albert Bourla, Pfizer CEO (Laurent Gillieron/Keystone via AP)

Break­ing: Pfiz­er in hot pur­suit of a $5B buy­out of Glob­al Blood Ther­a­peu­tics — re­port

Pfizer CEO Albert Bourla has vowed to leave no stone unturned in the search for new biotech deals, and the BD team is not letting him down.

The Wall Street Journal reported today that Pfizer is in the final stages of acquiring Global Blood Therapeutics for $5 billion. According to the Journal report, though, Pfizer is not the only buyer at the deal table and while the pharma giant may be close to clinching it, there are no guarantees it will continue.

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Al Sandrock, Voyager Therapeutics CEO

Al San­drock prunes his post-Bio­gen voy­age with sim­i­lar fo­cus on ALS

Al Sandrock is narrowing the focus of Voyager Therapeutics, concentrating on CNS diseases that were the hallmark of his time leading R&D at Biogen, including an emphasis on a familial form of ALS for which his former employer is getting a speedy review at the FDA.

Less than six months into his journey as CEO at Voyager, Sandrock is focusing the preclinical pipeline on Alzheimer’s disease, GBA1 Parkinson’s disease and SOD1 amyotrophic lateral sclerosis, the rare form of ALS for which the FDA will decide whether to approve Biogen’s tofersen by Jan. 25, 2023.

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George Yancopoulos, Regeneron president and CSO (Brendan McDermid/Reuters/Alamy)

George Yan­copou­los says he's on the trail of the holy grail: ‘This could rep­re­sent the next break­through for im­munother­a­py’

Two of the most outspoken — and successful — drug developers in biotech say they’ve collected early-stage clinical data that are pointing them down the trail to the holy grail in cancer immunotherapy R&D.

While analysts largely busied themselves today with chronicling the ongoing success of Regeneron’s two big cash cows — Dupixent and Eylea — chief scientist George Yancopoulos and CEO Len Schleifer used the Q2 call to spotlight their early success with a combination of the “homegrown” PSMAxCD28 costimulatory bispecific antibody REGN5678 in combination with their PD-1 checkpoint Libtayo. The presentation comes just weeks after Regeneron completed a deal to gather all rights to the PD-1 that had been in Sanofi’s hands. And the two top execs are unstinting in their praise of the potential of a whole set of costimulatory pipeline projects which they say may finally deliver the long-awaited next-level approach to broadening the immunotherapy field of drugs.

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(AP Photo/Richard Vogel, File)

US de­clares mon­key­pox a na­tion­al health emer­gency, as new drug­mak­ers con­sid­er en­ter­ing vac­cine race

Rising monkeypox cases have put the US on high alert as it announces a national health emergency, which grants the government more power in its response.

The news comes as Bavarian Nordic continues to fill orders for its Jynneos vaccine and other companies – including Moderna – consider jumping into the vaccine race. Meanwhile, the New York Times reports that the US has allowed around 20 million doses of smallpox vaccine in its stockpile to expire.

David Hallal (L) and George Daley (Hallal photo: Bertrand Guay/AFP via Getty Images)

David Hal­lal's El­e­vate­Bio launch­es new com­pa­ny to 'dis­rup­t' off-the-shelf cell ther­a­py, but pro­vides few oth­er de­tails

David Hallal’s ElevateBio is launching a new company Thursday as it looks to continue making its mark in the cell and gene therapy spaces. But Hallal is also keeping his cards close to the vest, preferring to toe the line between bombast and mystique rather than going all-in in one direction.

The new company comes out of a partnership with Boston Children’s Hospital and research from George Daley, the dean of Harvard Medical School. The triumvirate claims to have found a way to design better off-the-shelf cell therapies using new methods discovered in Daley’s Boston Children’s Hospital lab (Harvard is not involved in the collaboration).

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