Strike three: Bris­tol-My­ers’ third I/O shot at glioblas­toma miss­es as Op­di­vo flops yet again on key end­point

Glioblas­toma con­tin­ues to de­fy about every­thing thrown at it.

Bris­tol-My­ers Squibb put out word Thurs­day morn­ing that its third Phase III as­sault on brain can­cer us­ing its star PD-1 Op­di­vo failed the first end­point, with no sig­nif­i­cant im­prove­ment in pro­gres­sion-free sur­vival for pa­tients who face grim odds.

Check­Mate-548 ap­pears head­ed for a com­plete col­lapse, though over­all sur­vival is still be­ing stud­ied. Re­searchers had tried to see if the check­point ther­a­py could out­do the stan­dard of care by adding it to the stan­dard — temo­zolo­mide and ra­di­a­tion ther­a­py. 

They al­ready tried — and failed — ear­li­er this year with Check­Mate-498, a Phase III that com­bined Op­di­vo and ra­di­a­tion against temo­zolo­mide. That tri­al failed the mark on OS in May.

Two years ago the com­pa­ny was forced to con­cede de­feat on Check­mate-143, the first use of a PD-1 against glioblas­toma.

Bris­tol-My­ers has had a string of set­backs in the clin­ic with Op­di­vo, though the phar­ma gi­ant still en­joys block­buster rev­enue even as Mer­ck’s Keytru­da con­tin­ues its clin­i­cal blitz that put them on top of the mar­ket.

In this case, though, the Bris­tol-My­ers team joins a long list of fail­ures in fight­ing brain can­cer, which re­mains one of the tough­est tar­gets in on­col­o­gy. Ab­b­Vie had its own bit­ter set­back to re­port in May when their an­ti­body-drug con­ju­gate de­patux­izum­ab mafodotin (or de­patux-m; pre­vi­ous­ly known as ABT-414) al­so failed in im­prov­ing sur­vival times for brain can­cer vic­tims.

Sev­er­al years ago Ab­b­Vie showed up at AS­CO with ABT-414 and Ro­va-T to tout their po­ten­tial. Ro­va-T failed com­plete­ly for the R&D team, forc­ing a com­plete write-off of a drug they bought for $5.8 bil­lion up­front.

Robert Prins UCLA

A com­plete fail­ure here won’t ex­tin­guish all hope that a PD-1 could yet play a role in glioblas­toma. Robert Prins at the UCLA Jon­s­son Com­pre­hen­sive Can­cer Cen­ter re­port­ed ev­i­dence ear­li­er this year from a tiny ex­plorato­ry tri­al that a check­point may help pa­tients when used ahead of surgery. But it’s a long shot.

One of the few re­main­ing Phase III stud­ies for glioblas­toma like­ly to read out soon be­longs to Toca­gen $TO­CA which is mak­ing the dif­fi­cult as­sault with To­ca 511/FC. Re­searchers an­nounced sev­er­al months ago that they would con­tin­ue to the fi­nal read­out, dash­ing any hopes for an ear­ly suc­cess. There isn’t much con­fi­dence in this drug, though, with the stock falling from a high north of $15 last fall to just above $3 a share this morn­ing. The mar­ket cap is hold­ing at a mi­cro-lev­el $72 mil­lion.

These fail­ures won’t en­cour­age oth­ers to make a try.

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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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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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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George Yancopoulos (L) and Len Schleifer (Regeneron)

Re­gen­eron touts pos­i­tive pre­lim­i­nary im­pact of its Covid an­ti­body cock­tail, pre­vent­ing symp­to­matic in­fec­tions in high-risk group

Regeneron flipped its cards on an interim analysis of the data being collected for its Covid-19 antibody cocktail used as a safeguard against exposure to the virus. And the results are distinctly positive.

The big biotech reported Tuesday morning that their casirivimab and imdevimab combo prevented any symptomatic infections from occurring in a group of 186 people exposed to the virus through a family connection, while the placebo arm saw 8 of 223 people experience symptomatic infection. Symptomatic combined with asymptomatic infections occurred in 23 people among the 223 placebo patients compared to 10 of the 186 subjects in the cocktail arm.

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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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As­traZeneca scores new goal on the pipeline front, adding its first AI-gen­er­at­ed tar­get to the port­fo­lio

As more and more biopharmas develop artificial intelligence platforms, the drug discovery process is being reshaped to fit new goals on cutting down the prodigious amount of time, energy and money that go into a drug program. Now one of the most ambitious players in the drive to improve on ROI, AstraZeneca, is marking a milestone on that front by adding the first target generated by AI to its portfolio.

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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