New safe­ty da­ta ex­pose po­ten­tial weak­ness as Pfiz­er's abroc­i­tinib takes on Dupix­ent in eczema

Last Sep­tem­ber, when Pfiz­er cel­e­brat­ed pos­i­tive da­ta from a sec­ond Phase III study of abroc­i­tinib, many watch­ers ap­plaud­ed the ef­fi­ca­cy but were still wait­ing to see whether the JAK1 in­hibitor is “safe enough to be a for­mi­da­ble com­peti­tor to Dupix­ent,” the clear leader in the atopic der­mati­tis field. The full slate of safe­ty da­ta are now out and, ac­cord­ing to one an­a­lyst, the an­swer is: prob­a­bly not.

The broad­er class of JAK in­hibitors has been plagued by se­ri­ous side ef­fects re­lat­ing to blood that threat­en to lim­it their adop­tion, and JAK1 drugs — which tar­get a more spe­cif­ic sub­type of the ki­nase — are still un­der heavy scruti­ny.

In a note, Jef­feries’ Re­gen­eron bull Biren Amin sin­gled out re­duc­tions in platelet count in JADE MONO-2 as a par­tic­u­lar cause for con­cern.

At week 4, platelet re­duc­tions of 26% were not­ed for the 200mg dose, 19% in the 100mg group, and less than 1% for those on place­bo. In the drug’s de­fense, the re­searchers wrote that platelet counts “re­turned to­wards base­line val­ues there­after de­spite con­tin­u­a­tion of treat­ment,” and that there were no re­ports of bleed­ing dis­or­ders in any treat­ment group.

Still, the fact that the mech­a­nism lead­ing to platelet re­duc­tions is un­known could be a con­cern, Amin not­ed.

Then there’s the da­ta point that 1.9% of pa­tients in the 100mg group re­port­ed a se­ri­ous in­fec­tion, com­pared to none on 200mg and 1.3% on place­bo. Her­pes zoster was ob­served in 2 pa­tients tak­ing 200mg (1.3%).

In Ab­b­Vie’s case, Amin point­ed out, 1% of pa­tients re­port­ing se­ri­ous in­fec­tions, op­por­tunis­tic in­fec­tions and her­pes zoster was enough for reg­u­la­tors to slap a black box warn­ing on Rin­voq’s rheuma­toid arthri­tis la­bel.

“Tak­en to­geth­er, giv­en the safe­ty sig­nals around con­cerns for JAK1i class, ini­tial adop­tion of abroc­i­tinib might be lim­it­ed to se­vere pa­tients or on­ly be used as a short course of in­duc­tion be­fore switch­ing pa­tients to oth­er ther­a­pies to re­duce the ex­po­sure,” he wrote.

For now, Pfiz­er is fo­cus­ing on the bright side, em­pha­siz­ing how abroc­i­tinib can of­fer po­ten­tial symp­tom re­lief to pa­tients — in­clud­ing the both­er­some itch that comes with mod­er­ate to se­vere atopic der­mati­tis. The rate of ad­verse events over­all was al­so low in the tri­al, back­ing the claim that the drug was well-tol­er­at­ed. Abroc­i­tinib is al­so giv­en in pill form rather than sub­cu­ta­neous­ly, of­fer­ing pa­tients a more con­ve­nient choice.

But as Sanofi and Re­gen­eron con­tin­ue to groom Dupix­ent — the prize gem of a fore­gone re­la­tion­ship that gen­er­at­ed $2.32 bil­lion in 2019 rev­enue — in­to an even big­ger block­buster, the fight is on­ly be­gin­ning to play out.

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.

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.

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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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.

Scoop: Gilead ter­mi­nates ear­ly-stage FLT3 tri­al in sol­id tu­mors

Gilead chopped a Phase Ib dose escalation study in recent days, with an update to the federal trials database saying the premature termination followed an “internal safety assessment.”

The IV-administered FLT3 agonist, dubbed GS-3583, was being tested as a monotherapy in 13 patients with advanced solid tumors. The goal of the trial was to find out what dose to test in a Phase II, or maximum tolerated dose.

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

As­traZeneca’s Su­san Gal­braith high­lights twin wins for the can­cer drug pipeline at SABCS, as oral SERD ex­cels

It’s a good time to be the head of R&D for oncology at AstraZeneca. And no one gets that quite like Susan Galbraith.

Today, Galbraith is at the San Antonio Breast Cancer Symposium, highlighting the data on two key drugs in the cancer pipeline: mid-stage results for its oral SERD camizestrant among patients after one line of therapy, and the AKT drug capivasertib, wrapping the Phase III. Both fall neatly into the range of successes, beating out fulvestrant in hormone receptor-positive, HER2-negative breast cancer.

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