Wel­come Imfinzi: As­traZeneca crash­es the check­point par­ty late with a green light for dur­val­um­ab

And then there were 5.

The FDA hand­ed out its lat­est ap­proval for a PD-L1 check­point in­hibitor on Mon­day af­ter­noon, giv­ing a green light to As­traZeneca to start sell­ing dur­val­um­ab as Imfinzi as a sec­ond-line ther­a­py for metasta­t­ic urothe­lial car­ci­no­ma.

Pas­cal So­ri­ot

The reg­u­la­to­ry OK comes in the wake of ap­provals for Mer­ck, Bris­tol-My­ers Squibb, Roche/Genen­tech and Pfiz­er/Mer­ck KGaA. The bi­ol­o­gy of these new check­point drugs is well un­der­stood now, and the FDA is­sued its ap­proval af­ter a rel­a­tive­ly small, sin­gle-arm study.

Reg­u­la­tors waved this one through af­ter giv­ing dur­val­um­ab a break­through drug des­ig­na­tion and pri­or­i­ty re­view, even though its the third ap­proval for a check­point ther­a­py in blad­der can­cer.

Dur­val­um­ab’s longterm suc­cess is cru­cial to the fu­ture of As­traZeneca and CEO Pas­cal So­ri­ot. Billed as a block­buster-to-be, fol­low­ing a com­mer­cial trail al­ready clear­ly laid out, the big show­down for As­traZeneca comes lat­er in the year, when it rolls out late-stage da­ta on a com­bi­na­tion of its check­point com­bo in its MYS­TIC study, which match­es dur­val­um­ab with treme­li­mum­ab, a CT­LA-4 sim­i­lar to Yer­voy, for lung can­cer.

The ju­ry is still out, though, on how well a CT­LA-4 drug — with all its at­ten­dant tox­i­c­i­ty — will do in this field. That’s one rea­son why Bris­tol-My­ers Squibb re­cent­ly inked a deal with Cy­tomX on a next-gen CT­LA-4 that might prove far bet­ter for pa­tients.

Sea­mus Fer­nan­dez at Leerink not­ed some mod­est ex­pec­ta­tions on this first ap­proval. The up­side lies fur­ther down the road.

Al­though this in­di­ca­tion rep­re­sents a rel­a­tive­ly small op­por­tu­ni­ty for AZN (we fore­cast Imfinzi cap­tur­ing 10% of our es­ti­mat­ed ~$2.3B WW blad­der can­cer mar­ket), the ap­proval will al­low the agent to be­come more fa­mil­iar with on­col­o­gists and should help fa­cil­i­tate fu­ture sBLAs for drug. The ma­jor in­di­ca­tion for Imfinzi re­mains first-line (1L) non-small cell lung can­cer (NSCLC) and we await top-line da­ta from the Phase 3 MYS­TIC tri­al in com­bi­na­tion with treme­li­mum­ab (an­ti-CT­LA-4) ex­pect­ed in mid-2017.

As­traZeneca, mean­while, raised a red flag last week when it de­layed its third-line read­out in the ARC­TIC study of the duo, spurring some sus­pi­cions that it was on track to a trou­bling fail­ure that would have raised se­ri­ous doubts about its fu­ture in the field.

The oth­er ques­tion that many of us have is how many of these PD-1/PD-L1 check­points can be ap­proved be­fore they start slic­ing and dic­ing this mar­ket in­to ever small­er bites. A range of sec­ond-wave check­points are in de­vel­op­ment now, with every­one that’s fi­nanced well enough and in­ter­est­ed in it go­ing af­ter one of their own.

That group in­cludes In­cyte, which has been part­ner­ing with the main­stream check­points in nonex­clu­sive arrange­ments. And the main play­ers, like Mer­ck and Bris­tol-My­ers, are al­ready well along with their own com­bi­na­tion tri­als. Hun­dreds of them.

The ap­proval, though, marks a big win for As­traZeneca, which has made sig­nif­i­cant progress on the on­col­o­gy front in the last few years. They had to have this one to re­main a cred­i­ble ri­val. And they got it.

The FDA has been on a drug ap­proval spree over the last few days. This is the fifth OK for a new chem­i­cal en­ti­ty in the last three work­ing days, bring­ing the year-to-date to­tal to 19. Last year, which saw a big dip in ap­provals, the FDA ap­proved a to­tal of 22 new drugs.

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Pfiz­er's big block­buster Xel­janz flunks its post-mar­ket­ing safe­ty study, re­new­ing harsh ques­tions for JAK class

When the FDA approved Pfizer’s JAK inhibitor Xeljanz for rheumatoid arthritis in 2012, they slapped on a black box warning for a laundry list of adverse events and required the New York drugmaker to run a long-term safety study.

That study has since become a consistent headache for Pfizer and their blockbuster molecule. Last year, Pfizer dropped the entire high dose cohort after an independent monitoring board found more patients died in that group than in the low dose arm or a control arm of patients who received one of two TNF inhibitors, Enbrel or Humira.

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Covid-19 roundup: EU and As­traZeneca trade blows over slow­downs; Un­usu­al unions pop up to test an­ti­bod­ies, vac­cines

After coming under fire for manufacturing delays last week, AstraZeneca’s feud with the European Union has spilled into the open.

The bloc accused the pharma giant on Wednesday of pulling out of a meeting to discuss cuts to its vaccine supplies, the AP reported. AstraZeneca denied the reports, saying it still planned on attending the discussion.

Early Wednesday, an EU Commission spokeswoman said that “the representative of AstraZeneca had announced this morning, had informed us this morning that their participation is not confirmed, is not happening.” But an AstraZeneca spokesperson later called the reports “not accurate.”

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Pascal Soriot, AP

As­traZeneca CEO Pas­cal So­ri­ot sev­ers an un­usu­al board con­nec­tion, steer­ing clear of con­flicts while re­tain­ing im­por­tant al­liances

CSL Behring chief Paul Perreault scored an unusual coup last summer when he added AstraZeneca CEO Pascal Soriot to the board, via Zoom. It’s rare, to say the least, to see a Big Pharma CEO take any board post in an industry where interests can simultaneously connect and collide on multiple levels of operations.

The tie set the stage for an important manufacturing connection. The Australian pharma giant agreed to supply the country with 10s of millions of AstraZeneca’s Covid-19 vaccine, once it passes regulatory muster.

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Adeno-associated virus-1 illustration; the use of AAVs resurrected the gene therapy field, but companies are now testing the limits of a 20-year-old technology (File photo, Shutterstock)

Af­ter 3 deaths rock the field, gene ther­a­py re­searchers con­tem­plate AAV's fu­ture

Nicole Paulk was scrolling through her phone in bed early one morning in June when an email from a colleague jolted her awake. It was an article: Two patients in an Audentes gene therapy trial had died, grinding the study to a halt.

Paulk, who runs a gene therapy lab at the University of California, San Francisco, had planned to spend the day listening to talks at the American Association for Cancer Research annual meeting, which was taking place that week. Instead, she skipped the conference, canceled every work call on her calendar and began phoning colleagues across academia and industry, trying to figure out what happened and why. All the while, a single name hung in the back of her head.

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Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

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Anthony Fauci, NIAID director (AP Images)

As new Covid-19 task force gets un­der­way, threat looms of vac­cine, mon­o­clon­al an­ti­body-re­sis­tant vari­ants

Hours before President Biden’s Covid-19 team gave their first virtual press conference, the famed AIDS researcher David Ho delivered concerning news in a new pre-print: SARS-CoV-2 B.1.351, the variant that emerged in South Africa, is “markedly more resistant” to antibodies from convalescent plasma and vaccinated individuals.

The news for several monoclonal antibodies, including Eli Lilly’s bamlanivimab, was even worse: Their ability to neutralize was “completely or markedly abolished,” Ho wrote. Lilly’s antibody cocktail, which was just shown to dramatically reduce the risk of hospitalizations or death, also became far less potent.

Jackie Fouse, Agios CEO

Agios scores its sec­ond pos­i­tive round of da­ta for its lead pipeline drug — but that won't an­swer the stub­born ques­tions that sur­round this pro­gram

Agios $AGIO bet the farm on its PKR activator drug mitapivat when it recently decided to sell off its pioneering cancer drug Tibsovo and go back to being a development-stage company — for what CEO Jackie Fouse hoped would be a short stretch before they got back into commercialization.

On Tuesday evening, the bellwether biotech flashed more positive topline data — this time from a small group of patients in a single-arm study. And the executive team plans to package this with its earlier positive results from a controlled study to make its case for a quick OK.

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Drug­mak­ers 'inch­ing ahead' in in­creas­ing ac­cess to drugs world­wide, with Glax­o­SmithK­line lead­ing the pack

Top drug developers are “inching ahead” in improving access to much-needed drugs around the world — an issue that has been underscored by the Covid-19 pandemic. But there’s still more work to do, Access to Medicine Foundation executive director Jayasree Iyer said.

Every two years, the Access to Medicines Index ranks the top 20 biotechs leading the push for better access to medicines in low- and middle-income countries. This year’s report, published Tuesday, looks at drug access in 106 countries.