Adap­ti­m­mune looks to sal­vage ovar­i­an can­cer study by adding flu­dara­bine to prep pa­tients

CMO Rafael Ama­do

The use of flu­dara­bine was fin­gered as a key cul­prit in the deaths of sev­er­al pa­tients tak­ing Juno’s lead CAR-T ther­a­py, but it’s an ab­solute­ly vi­tal part of the pre­con­di­tion­ing reg­i­men be­ing used to pre­pare pa­tients for the wave of new cell ther­a­pies now in the clin­ic for can­cer. And Adap­ti­m­mune $ADAP helped un­der­score just how crit­i­cal it is to­day, say­ing that it’s read­just­ing its tri­al pro­to­col for its T-cell ther­a­py for ovar­i­an can­cer, adding flu­dara­bine to the com­bi­na­tion af­ter fail­ing to get any ini­tial re­spons­es in pa­tients with­out it.

Chief Med­ical Of­fi­cer Rafael Ama­do put it this way:

“We hope that, as pre­vi­ous­ly ob­served in syn­ovial sar­co­ma, this lym­phode­plet­ing reg­i­men will en­able an­ti-tu­mor im­mune re­spons­es me­di­at­ed by NY-ESO SPEAR T-cell ther­a­py in these pa­tients with ad­vanced chemother­a­py re­lapsed or re­frac­to­ry ovar­i­an can­cer.”

Shares of Adap­ti­m­mune dropped 12% Wednes­day morn­ing.

This flu/cy com­bo has emerged as a cen­tral fea­ture in cell ther­a­pies. By us­ing the com­bo on pa­tients, in­ves­ti­ga­tors have seen clear signs that their cell ther­a­pies are bet­ter able to pop­u­late and durably at­tack can­cer cells. But you have to get the mix of flu/cy plus the right dosage of your cell ther­a­py bal­anced prop­er­ly to avoid killing pa­tients.

When Juno $JUNO tried it, their recipe of flu/cy com­bined with JCAR015 killed three pa­tients by spurring cere­bral ede­ma. An­oth­er pa­tient in a sep­a­rate study al­so was killed by se­vere neu­ro­tox­i­c­i­ty, bring­ing the death count to 4. The FDA re­spond­ed by plac­ing the lead pro­gram on com­plete hold, then lift­ed the hold af­ter Juno pro­posed pulling flu­dara­bine from the mix.

That quick fix to get the hold lift­ed may have sig­nif­i­cant­ly re­duced the threat of lethal tox­i­c­i­ty, but Juno’s ri­val Kite $KITE has man­aged to forge ahead with its own bal­anc­ing act of flu/cy com­bined with their lead CAR-T. And it seems clear that any ther­a­pies that don’t use flu/cy may be at a com­pet­i­tive dis­ad­van­tage. At the time, Jef­feries’ Biren Amin not­ed:

“Crit­i­cal­ly, we al­so know that a flu/cy reg­i­men much high­er than what Kite us­es in their tri­als (rough­ly four times more cy for ALL pa­tients) was in­volved in all four cere­bral ede­ma cas­es (at Juno).”

Adap­ti­m­mune now plans to add 10 more pa­tients to its small Phase I/II study to see how they will re­spond to the new ther­a­peu­tic reg­i­men. The UK biotech – with R&D ops in Philadel­phia – had to put one tri­al for myx­oid round cell li­posar­co­ma on par­tial hold on or­ders from the FDA in Au­gust, af­ter reg­u­la­tors said they had some tri­al de­sign ques­tions to clear up be­fore pa­tients could be treat­ed.

Paul Hudson, Sanofi CEO (Romuald Meigneux/Sipa via AP Images)

Sanofi and DN­Di aim to elim­i­nate sleep­ing sick­ness in Africa with promis­ing Ph II/III re­sults for new drug

The Drugs for Neglected Diseases initiative (DNDi) and Sanofi today said that their potential sleeping sickness treatment saw success rates of up to 95% from a Phase II/III study investigating the safety and efficacy of single-dose acoziborole.

The potentially transformative treatment for sleeping sickness would mainly be targeted at African countries, according to data published today in The Lancet Infectious Diseases medical journal. The clinical trial was led by DNDi and its partners in the Democratic Republic of the Congo (DRC) and Guinea, with the authors noting:

Susan Galbraith, AstraZeneca EVP, oncology R&D, at EUBIO22 (Rachel Kiki for Endpoints News)

Up­dat­ed: As­traZeneca jumps deep­er in­to cell ther­a­py 2.0 space with $320M biotech M&A

Right from the start, the execs at Neogene had some lofty goals in mind when they decided to try their hand at a cell therapy that could tackle solid tumors.

Its founders have helped hone a new approach that would pack in multiple neoantigen targets to create a personalized TCR treatment that would not just make the leap from blood to solid tumors, but do it with durability. And they managed to make their way rapidly to the clinic, unveiling their first Phase I program for advanced tumors just last May.

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Ei­sai’s ex­pand­ed Alzheimer’s da­ta leave open ques­tions about safe­ty and clin­i­cal ben­e­fit

Researchers still have key questions about Eisai’s investigational Alzheimer’s drug lecanemab following the publication of more Phase III data in the New England Journal of Medicine Tuesday night.

In the paper, which was released in conjunction with presentations at an Alzheimer’s conference, trial investigators write that a definition of clinical meaningfulness “has not been established.” And the relative lack of new information, following topline data unveiled in September, left experts asking for more — setting up a potential showdown to precisely define how big a difference the drug makes in patients’ lives.

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Pro­tect­ing its megablock­buster, Janssen chal­lenges Am­gen's Ste­lara biosim­i­lar ahead of planned 2023 launch

Johnson & Johnson unit Janssen on Wednesday sued Amgen over the company’s proposed biosimilar to its megablockbuster Stelara (ustekinumab), after Amgen said it was ready to launch next May or as soon as the FDA signs off on it.

If Amgen carries through with that plan, Janssen told the Delaware district court that the Thousand Oaks, CA-based company will infringe on at least two Janssen patents.

Lex­i­con slams FDA over hear­ing de­nial fol­low­ing a CRL for its SGLT2 in­hibitor can­di­date

Lexicon Pharmaceutical is not giving up on its Type I diabetes candidate, despite FDA’s repeated rejections. This week the company laid out is argument again for a hearing on sotagliflozin in response to the FDA’s most recent denial.

The issue goes back to March 2019 when the FDA made very clear to Lexicon and its now departed partner Sanofi that it would not approve their application for a potential Type I diabetes drug because it does not appear to be safe.

Digital render of CPI's Medicines Manufacturing Innovation Centre in Glasgow, Scotland (Image: uk-cpi.com)

CPI opens the doors to a new $100M+ man­u­fac­tur­ing fa­cil­i­ty in Scot­land

A manufacturing site that has received interest and investments from large pharma companies and the UK government is opening its doors in Scotland.

The manufacturer CPI (Centre for Process Innovation) has opened a new £88 million ($105 million) “Medicines Manufacturing Innovation Centre” in Glasgow, Scotland, to accelerate the development of manufacturing tech and solve longstanding challenges in medicine development and manufacturing.

Illustration: Assistant Editor Kathy Wong for Endpoints News

Twit­ter dis­ar­ray con­tin­ues as phar­ma ad­ver­tis­ers ex­tend paus­es and look around for op­tions, but keep tweet­ing

Pharma advertisers on Twitter are done — at least for now. Ad spending among the previous top spenders flattened even further last week, according to the latest data from ad tracker Pathmatics, amid ongoing turmoil after billionaire boss Elon Musk’s takeover now one month ago.

Among 18 top advertisers tracked for Endpoints News, only two are spending: GSK and Bayer. GSK spending for the full week through Sunday was minimal at just under $1,900. Meanwhile, German drugmaker Bayer remains the industry outlier upping its spending to $499,000 last week from $480,000 the previous week. Bayer’s spending also marks a big increase from a month ago and before the Musk takeover, when it spent $16,000 per week.

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Vi­a­tris with­draws ac­cel­er­at­ed ap­proval for top­i­cal an­timi­cro­bial 24 years lat­er

After 24 years without confirming clinical benefit, the FDA announced Tuesday morning that Viatris (formed via Mylan and Pfizer’s Upjohn) has decided to withdraw a topical antimicrobial agent, Sulfamylon (mafenide acetate), after the company said conducting a confirmatory study was not feasible.

Sulfamylon first won FDA’s accelerated nod in 1998 as a topical burn treatment, with the FDA noting that last December, Mylan told the agency that it wasn’t running the trial.

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John Carroll with David Chang, Allogene CEO (Credit: Jeff Rumans Photography)

Al­lo­gene takes the stage in New York to go deep on its off-the-shelf cell ther­a­pies — de­clar­ing a first for sol­id tu­mors

NEW YORK — In most cases, a biotech like Allogene would wait until the next big science conference to offer its latest series of snapshots of its data. But most biotechs aren’t like Allogene, where the veteran leaders from Kite garnered a substantial number of kudos over the years for their in-depth reviews of the company’s progress.

So on Tuesday, the leaders at Allogene converged on Manhattan once again to give a detailed breakdown of their latest steps forward, looking to stay out front in the busy off-the-shelf cell therapy arena, keep a clean bill of health on the safety front and prove that they can not only match the autologous pioneers they helped create but make the all-important leap into solid tumors. It’s another step forward in a journey that has a long way to go before even the first big regulatory finish lines appear on the track. But for CEO David Chang, who spent some time with me running through the data ahead of the Tuesday session, it all amounts to forward momentum toward the desired goal.

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