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.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

Stéphane Bancel, Moderna CEO

'This is not go­ing to be good': Mod­er­na CEO Ban­cel warns of a 'ma­te­r­i­al drop' in vac­cine ef­fi­ca­cy as Omi­cron spreads

Even as public health officials remain guarded about their comments on the likelihood Omicron will escape the reach of the currently approved Covid-19 vaccines, there’s growing scientific consensus that we’re facing a variant that threatens to overwhelm the vaccine barricades that have been erected.

Stéphane Bancel, the CEO of Moderna, one of the leading mRNA players whose quick vault into the markets with a highly effective vaccine created an instant multibillion-dollar market, added his voice to the rising chorus early Tuesday. According to Bancel, there will be a significant drop in efficacy when the average immune system is confronted by Omicron. The only question now is: How much?

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Philip Dormitzer, new GSK global head of vaccines R&D

Glax­o­SmithK­line poach­es Pfiz­er's vi­ral vac­cines lead in rush to cap­i­tal­ize on fu­ture of mR­NA

GlaxoSmithKline has appointed Philip Dormitzer, formerly chief scientific officer of Pfizer’s viral vaccines unit, as its newest global head of vaccines R&D, looking to leverage one of the leading minds behind Pfizer and BioNTech’s RNA collaboration that led to Covid-19 jab Comirnaty, the British drug giant said Tuesday.

Dormitzer had been with Pfizer for a little more than six years, joining up after a seven-year stint with Novartis, where he reached the role of US head of research and head of global virology for the company’s vaccines and diagnostics unit.

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In­tro­duc­ing End­points Stu­dio, a new way to ad­ver­tise with End­points-craft­ed brand­ing cam­paigns

Since our start in 2016, Endpoints has grown fast while executing our mission to cover biopharma’s most critical developments for industry pros worldwide. As readership has grown, our advertising business has too. Endpoints advertising partners support the mission and engage their desired audiences through announcements on our email and web platforms, brand recognition in our event coverage and sponsorships of Endpoints daily and weekly reports.

As lead drug runs in­to a wall, De­ci­phera slims down its pipeline, puts 140 jobs on the chop­ping block

Barely a month after disappointing data shattered hopes for a major label expansion for the GI tumor drug Qinlock, Deciphera is making a major pivot — scrapping development plans for that drug and discarding another while it hunkers down and focuses on two remaining drugs in the pipeline.

As a result, 140 of its staffers will be laid off.

The restructuring, which claims the equivalent of 35% of its total workforce, will take place across all departments including commercial, R&D as well as general and administrative support functions, Deciphera said, as it looks to streamline Qinlock-related commercial operations in the US while concentrating only on a “select number of key European markets.”

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How to use reg­istry da­ta to sup­port FDA de­ci­sion mak­ing: Agency ex­plains in new guid­ance

Drugmakers looking to design a new registry or use an existing one to support a regulatory decision on a drug’s effectiveness or safety will need to consult with a new draft guidance released Monday by the FDA.

The agency’s reliance on registry data for regulatory decisions dates back more than two decades, at least, as in 1998 Bayer won approval for its anticoagulant Refludan (withdrawn from the market in 2013 for commercial reasons) based in part on a historical control group pulled from a registry.

Tillman Gerngross (Adagio)

Till­man Gern­gross on Omi­cron: 'It is a grim sit­u­a­tion...we’re go­ing to see a sig­nif­i­cant drop in vac­cine ef­fi­ca­cy'

Tillman Gerngross, the rarely shy Dartmouth professor, biotech entrepreneur and antibody expert, has been warning for over a year that the virus behind Covid-19 would likely continue to mutate, potentially in ways that avoid immunity from infection and the best defenses scientists developed. He spun out a company, Adagio, to build a universal antibody, one that could snuff out any potential mutation.

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In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

Mar­ket­ingRx roundup: Ab­b­Vie’s Hu­mi­ra TV turns fo­cus to HS skin con­di­tion; Sanofi amps par­ent­ing pol­i­cy

After years as the top spending pharma TV advertiser, AbbVie’s Humira brand finally downshifted earlier this year, ceding much of its marketing budget to up-and-coming sibling meds Skyrizi and Rinvoq. However, now Humira is back on TV with ads for another condition — Hidradenitis suppurativa (HS).

The chronic and painful skin condition results in lumps and abscesses caused by inflammation or infection of sweat glands, most often in the armpits or groin. Humira was first approved to treat HS in 2015 and remains the only FDA-approved drug for the condition. Two TV ads both note more than 30,000 people with HS have been prescribed Humira.