Samit Hirawat. Bristol-Myers Squibb

Bris­tol-My­ers is mak­ing a bee-line to the FDA with pos­i­tive liso-cel da­ta — but is it too late in the CAR-T game?

Bris­tol-My­ers Squibb came to ASH this past week­end with a va­ri­ety of mes­sages on the new can­cer drugs they had ac­quired in the big Cel­gene buy­out, in­clud­ing liso-cel, the lead CAR-T pro­gram picked up in the $9 bil­lion Juno ac­qui­si­tion. And one of the most im­por­tant was that they had the piv­otal ef­fi­ca­cy and safe­ty da­ta need­ed to snag an ap­proval from the FDA next year, with the BLA on track for a fil­ing this month.

Pro­vid­ed there are no sna­fus or even mod­est stum­bles now, they should get an OK with­in the 2020 time­line lined out in their $9 CVR for Cel­gene — the first in a tri­fec­ta of ap­provals re­quired for a pay­out.

Whether they can go on to make it in­to a vi­able com­mer­cial ther­a­py, though, is a whole oth­er thing.

At first glance, there isn’t any­thing about the safe­ty and ef­fi­ca­cy da­ta that would force a CRL or de­lay. In a large tri­al of pa­tients with re­lapsed/re­frac­to­ry large B-cell lym­phomas in­ves­ti­ga­tors tracked an out­stand­ing 73% re­sponse rate and 53% com­plete re­sponse rate in heav­i­ly pre­treat­ed pa­tients with few op­tions.

That’s in line with Yescar­ta from Gilead’s Kite, which snagged an ap­proval more than 2 years ago, just af­ter No­var­tis’ Kym­ri­ah came through.

Then there’s safe­ty. To be sure, the drug has safe­ty is­sues. There were 4 pa­tients in the study who died af­ter treat­ment. Sev­er­al oth­ers died for un­re­lat­ed is­sues. But…with on­ly a 2% rate of cy­tokine re­lease syn­drome, Bris­tol-My­ers has a shot at a dif­fer­en­ti­at­ed safe­ty pro­file.

“There is a po­ten­tial these pa­tients can be treat­ed on an out­pa­tient ba­sis,” says Samit Hi­rawat, the chief med­ical of­fi­cer at Bris­tol-My­ers. He not­ed that 26% of pa­tients were nev­er ad­mit­ted, while 76% were ad­mit­ted 4 days or lat­er af­ter ther­a­py. The key is to treat them at a hos­pi­tal with the in­fra­struc­ture to pro­vide care 24/7, so a pa­tient can be ad­mit­ted at any time lat­er if need­ed.

How that will fly with pay­ers af­ter ri­vals have been on the mar­ket for about 3 years, with new ev­i­dence that ear­li­er use of steroids can dra­mat­i­cal­ly re­duce CRS and con­sid­er­able dura­bil­i­ty of re­sponse, will have to be seen.

But time is not on Bris­tol-My­ers’ side. Liso-cel is the long de­layed fol­lowup to the dis­as­trous JCAR015, which killed a num­ber of pa­tients. Their set­back threw them years off sched­ule. And ri­vals are ad­vanc­ing off-the-shelf al­ter­na­tives or oth­er new ap­proach­es that could knock the pi­o­neers com­plete­ly out of the game. In the mean­time, Bris­tol-My­ers is gath­er­ing its own dura­bil­i­ty da­ta and will grad­u­al­ly see if their mix of CD4 and CD8 cells can do bet­ter.

The main in­ter­est now is in the time­line around the ap­proval. Hi­rawat says they’ll ask for pri­or­i­ty re­view, and there’s every rea­son to be­lieve that reg­u­la­tors will move swift­ly — bar­ring a nasty sur­prise.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Dipal Doshi, Entrada Therapeutics CEO

Ver­tex just found the next big ‘trans­for­ma­tive’ thing for the pipeline — at a biotech just down the street

Back in the summer of 2019, when I was covering Vertex’s executive chairman Jeff Leiden’s plans for the pipeline, I picked up on a distinct focus on myotonic dystrophy Type I, or DM1 — one of what Leiden called “two diseases (with DMD) we’re interested in and we continue to look for those assets.”

Today, Leiden’s successor at the helm of Vertex, CEO Reshma Kewalramani, is plunking down $250 million in cash to go the extra mile on DM1. The lion’s share of that is for the upfront, with a small reserve for equity in a deal that lines Vertex up with a neighbor in Seaport that has been rather quietly going at both of Vertex’s early disease targets with preclinical assets.

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Rami Elghandour, Arcellx CEO

Up­dat­ed: Gilead, Ar­cel­lx team up on an­ti-BC­MA CAR-T as biotech touts a 100% re­sponse rate at #ASH22

Gilead and Kite are plunking down big cash to get into the anti-BCMA CAR-T game.

The pair will shell out $225 million in cash upfront and $100 million in equity to Arcellx, Kite announced Friday morning, to develop the biotech’s lead CAR-T program together. Kite will handle commercialization and co-development with Arcellx, and profits in the US will be split 50-50.

Concurrent with the deal, Arcellx revealed its latest cut of data for the program known as CART-ddBCMA, ahead of a full presentation at this weekend’s ASH conference — a 100% response rate among patients getting the therapy. Investors jumped at the dual announcements, sending Arcellx shares $ACLX up more than 25% in Friday’s morning session.

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Christian Itin, Autolus CEO (UKBIO19)

Au­to­lus tips its hand, bags $220M as CAR-T show­down with Gilead looms

The first batch of pivotal data on Autolus Therapeutics’ CAR-T is in, and execs are ready to plot a path to market.

With an overall remission rate of 70% at the interim analysis featuring 50 patients, the results set the stage for a BLA filing by the end of 2023, said CEO Christian Itin.

Perhaps more importantly — given that Autolus’ drug, obe-cel, is going after an indication that Gilead’s Tecartus is already approved for — the biotech highlighted “encouraging safety data” in the trial, with a low percentage of patients experiencing severe immune responses.

WIB22: Am­ber Salz­man had few op­tions when her son was di­ag­nosed with a rare ge­net­ic dis­ease. So she cre­at­ed a bet­ter one

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

Amber Salzman’s life changed on a cold, damp day in Paris over tiny plastic cups of lukewarm tea.

She was meeting with Patrick Aubourg, a French neurologist studying adrenoleukodystrophy, or ALD, a rare genetic condition that causes rapid neurological decline in young boys. It’s a sinister disease that often leads to disability or death within just a few years. Salzman’s nephew was diagnosed at just 6 or 7 years old, and died at the age of 12.

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Ahead of ad­comm, FDA rais­es un­cer­tain­ties on ben­e­fit-risk pro­file of Cy­to­ki­net­ic­s' po­ten­tial heart drug

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will meet next Tuesday to discuss whether Cytokinetics’ potential heart drug can safely reduce the risk of cardiovascular death and heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction.

The drug, known as omecamtiv mecarbil and in development for more than 15 years, has seen mixed results, with a first Phase III readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.

Ab­b­Vie slapped with age dis­crim­i­na­tion law­suit, fol­low­ing oth­er phar­mas

Add AbbVie to the list of pharma companies currently facing age discrimination allegations.

Pennsylvania resident Thomas Hesch filed suit against AbbVie on Wednesday, accusing the company of passing him over for promotions in favor of younger candidates.

Despite 30 years of pharma experience, “Hesch has consistently seen younger, less qualified employees promoted over him,” the complaint states.

WIB22: Lead­ing NK cell re­searcher re­flects on roots in Iran, the UK and Texas

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

In a small but widely-cited 11-person study published in NEJM in 2020, seven patients saw signs of their cancer completely go away after getting a new therapy made from natural killer cells. The study was one of the earliest to provide clinical proof that the experimental treatment method had promise.

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Philip Astley-Sparke, Replimune CEO

Replimune looks to rope in $225M on the back of melanoma da­ta

The Massachusetts-based, oncolytic virus biotech Replimune is feeling bullish now that it has lifted the cover on data for its lead product.

Replimune said Thursday it looks to nab about $225 million from a public offering after giving a snapshot of some initial data from its IGNYTE clinical study earlier this week. The trial is investigating RP1 in combination with Opdivo, for patients with melanoma and who did not have a response when being treated with a PD-1.