As­traZeneca and Am­gen qui­et­ly ad­mit teze­pelum­ab set­back as the Dupix­ent chal­lenger heads to FDA

As­traZeneca and Am­gen have block­buster am­bi­tions for their teze­pelum­ab an­ti­body, aim­ing to chal­lenge the Re­gen­eron and Sanofi gi­ant Dupix­ent in asth­ma and re­lat­ed res­pi­ra­to­ry mal­adies. But as part of its sec­ond quar­ter up­date Thurs­day morn­ing, the big British drug­mak­er qui­et­ly scut­tled plans in an­oth­er in­di­ca­tion, rais­ing doubt over how big a bite it will take out of the Dupix­ent pie.

Af­ter flunk­ing two Phase II stud­ies in atopic der­mati­tis, As­traZeneca dropped plans for teze­pelum­ab to treat the con­di­tion al­to­geth­er, the com­pa­ny re­vealed Thurs­day morn­ing. The move comes just a few weeks af­ter the an­ti­body won pri­or­i­ty re­view from the FDA in asth­ma, where a de­ci­sion is ex­pect­ed in the first quar­ter next year.

End­points News has reached out to As­traZeneca for com­ment and will up­date ac­cord­ing­ly.

Though teze­pelum­ab has — most­ly — passed all the nec­es­sary check­points in asth­ma, atopic der­mati­tis has been an­oth­er sto­ry al­to­geth­er. The first mis­step came back in 2017, when the an­ti­body whiffed on a Phase IIa pri­ma­ry end­point in AD, com­ing up short on an eczema mea­sure­ment scale com­pared to place­bo.

In this study, teze­pelum­ab was eval­u­at­ed over a 12-week pe­ri­od in 113 pa­tients with mod­er­ate to se­vere atopic der­mati­tis. Though a nu­mer­i­cal­ly greater por­tion of the drug arm saw im­prove­ment against place­bo plus top­i­cal cor­ti­cos­teroids, the can­di­date missed sta­tis­ti­cal sig­nif­i­cance with a p-val­ue of 0.091.

Then came a Phase IIb tri­al in 251 pa­tients look­ing at both a monother­a­py treat­ment course and an ad­junct reg­i­men, al­so in mod­er­ate to se­vere AD. This study was halt­ed some­time in the sec­ond quar­ter of 2020 due to fu­til­i­ty, ac­cord­ing to Am­gen’s earn­ings re­port at the time, with the phar­ma not­ing the study didn’t have any im­pact on asth­ma and COPD re­search.

By and large, that hy­poth­e­sis has held true. As­traZeneca and Am­gen won their pri­or­i­ty re­view based on a Phase III study that cut the rate of se­vere asth­ma at­tacks on top of stan­dard of care. Teze­pelum­ab al­so man­aged con­sis­tent re­sults re­gard­less of pa­tients’ base­line eosinophil counts and al­ler­gy sta­tus, an area where some an­a­lysts have sug­gest­ed the an­ti­body might have an ad­van­tage over the Re­gen­eron/Sanofi gi­ant.

David Reese

But the pro­gram al­so flopped a sep­a­rate Phase III study in the same pop­u­la­tion, a re­sult Am­gen R&D chief David Reese called “sur­pris­ing” last De­cem­ber. Though Reese at­trib­uted the miss to pos­si­ble tri­al de­sign flaws, an­a­lysts took a more pes­simistic look, not­ing that Dupix­ent had suc­cess­ful­ly re­duced cor­ti­cos­teroid use in a sim­i­lar tri­al.

As As­traZeneca and Am­gen con­tin­ue to chart a block­buster path — some peak sales fore­casts have pegged $2.5 bil­lion an­nu­al sales for the an­ti­body — they may strug­gle to reach the heights of com­peti­tors. Dupix­ent is ap­proved to treat eczema and atopic der­mati­tis and over­all sales in­creased a whop­ping 45% in the sec­ond quar­ter of 2021, Sanofi re­vealed Thurs­day.

That growth amount­ed to near­ly $1.5 bil­lion in the three-month pe­ri­od alone. It re­mains to be seen how quick the teze­pelum­ab up­take will be, but As­traZeneca and Am­gen are hop­ing for a quick and easy time at the FDA to get things go­ing.

Biotech and Big Phar­ma: A blue­print for a suc­cess­ful part­ner­ship

Strategic partnerships have long been an important contributor to how drugs are discovered and developed. For decades, big pharma companies have been forming alliances with biotech innovators to increase R&D productivity, expand geographical reach and better manage late-stage commercialization costs.

Noël Brown, Managing Director and Head of Biotechnology Investment Banking, and Greg Wiederrecht, Ph.D., Managing Director in the Global Healthcare Investment Banking Group at RBC Capital Markets, are no strangers to the importance of these tie-ups. Noël has over 20 years of investment banking experience in the industry. Before moving to the banking world in 2015, Greg was the Vice President and Head of External Scientific Affairs (ESA) at Merck, where he was responsible for the scientific assessment of strategic partnership opportunities worldwide.

No­var­tis' sec­ond at­tempt to repli­cate a stun­ning can­cer re­sult falls flat

Novartis’ hopes of turning one of the most surprising trial data points of the last decade into a lung cancer drug has taken another setback.

The Swiss pharma announced Monday that its IL-1 inhibitor canakinumab did not significantly extend the lives or slow the disease progression of patients with previously untreated locally advanced or metastatic non-small cell lung cancer when compared to standard of-care alone.

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How Chi­na turned the ta­bles on bio­phar­ma's glob­al deal­mak­ing

Fenlai Tan still gets chills thinking about the darkest day of his life.

Three out of eight lung cancer patients who received a tyrosine kinase inhibitor developed by his company, Betta Pharma, died in the span of a month. Tan, the chief medical officer, was summoned to Peking Union Medical College Hospital, where the head of the clinical trial department told him that the trial investigators would be conducting an autopsy to see if the patients had died of the disease — they were all very sick by the time they enrolled — or of interstitial lung disease, a deadly side effect tied to the TKI class that’s been reported in Japan.

An­gion's or­gan dam­age drug strikes out again, this time in high-risk kid­ney trans­plant pa­tients

After flopping a test in Covid-19 earlier this year, Angion’s lead organ damage drug has now hit the skids again in kidney transplant patients.

Angion and partner Vifor Pharma’s ANG-3777 failed to beat out placebo in terms of improving eGFR, a measure of kidney function, in patients who had received a deceased donor kidney transplant and were at high risk of developing what is known as delayed graft function, according to Phase III results released Tuesday.

An image of Alzheimer's brain tissue. The red show gingipains, a protein from P. gingivalis, intermixing with neurons (yellow) and glial cells (green)

An Alzheimer's dark­horse fails its first big tri­al, but of­fers hope for a long-over­looked hy­poth­e­sis

Three years ago, Cortexyme emerged out of obscurity with some big-name backers and an unorthodox approach to treating Alzheimer’s.

They moved their drug into a pivotal study the next year, offering one of the first major tests for a hypothesis that has fluttered on the outskirts of Alzheimer’s research for decades: that, in many cases, the disease is driven by infectious agents — the havoc they wreak in the brain and the inflammation the body uses to try to fend them off. And that quashing the infection could slow patients’ cognitive decline.

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No­var­tis dumps AveX­is pro­gram for Rett syn­drome af­ter fail­ing re­peat round of pre­clin­i­cal test­ing

Say goodbye to AVXS-201.

The Rett syndrome gene therapy drug made by AveXis — the biotech that was bought, kept separate, then renamed and finally absorbed by Novartis into its R&D division — has been dropped by the biopharma.

In Novartis’ third quarter financial report, the pharma had found that preclinical data did not support development of the gene therapy into IND-enabling trials and beyond. The announcement comes a year after Novartis told the Rett Society how excited it was by the drug — and its potential benefits and uses.

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Peter Nell, Mammoth Biosciences CBO

UP­DAT­ED: Jen­nifer Doud­na spin­out inks a Mam­moth CRISPR deal with Ver­tex worth near­ly $700M

When a company gets its start in gene editing pioneer Jennifer Doudna’s lab, it’s bound to make headlines. But three years in, the fanfare still hasn’t died down for Mammoth Biosciences. Now, the Brisbane, CA-based company is cheering on its first major R&D pact.

Mammoth unveiled a nearly $700 million deal with Vertex on Tuesday morning, good for the development of in vivo gene therapies for two mystery diseases. The stars of the show are Mammoth’s ultra-small CRISPR systems, including two Cas enzymes licensed from Doudna’s lab over the past couple years, Cas14 and Casɸ.

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FDA is much worse than its reg­u­la­to­ry peers at proac­tive­ly dis­clos­ing da­ta, re­searchers find

The European Medicines Agency and Health Canada continue to outpace the FDA when it comes to proactively releasing data on drugs and biologics the agency has reviewed, leading to further questions of why the American agency can’t be more transparent.

In a study published recently in the Journal of Law, Medicine, & Ethics, Yale and other academic lawyers and researchers found that between 2016 and April 2021, the EMA proactively released data for 123 unique medical products, while Health Canada proactively released data for 73 unique medical products between 2019 and April 2021. What’s more, the EMA and Health Canada didn’t proactively release the same data on the same drugs. In stark contrast, the FDA in 2018 only proactively disclosed data supporting one drug that was approved that year.

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NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.