In a stun­ning set­back, Roche says its top can­cer drug Tecen­triq failed a key PhI­II study

Genen­tech put the A team on their PD-L1 check­point pro­gram for Tecen­triq (ate­zolizum­ab), build­ing a pipeline of com­bi­na­tions now in the clin­ic as they raced to an ac­cel­er­at­ed ap­proval so they could be­gin mar­ket­ing in the boom­ing field. And this morn­ing, Roche says that the drug failed the late-stage con­fir­ma­to­ry study in blad­der can­cer, fail­ing to sig­nif­i­cant­ly im­prove over­all sur­vival and de­liv­er­ing a blow that rais­es ques­tions about the fate of this drug and their en­tire check­point R&D cam­paign.

Roche’s stock dropped 2% on the news.

What went wrong?

San­dra Horn­ing

Roche says it is study­ing that now, but not­ed in its state­ment that the chemo arm of the study ex­pe­ri­enced an un­usu­al­ly high re­sponse that wasn’t ex­pect­ed by the multi­na­tion­al com­pa­ny. The ac­cel­er­at­ed ap­proval — which the FDA not­ed could be yanked if the Phase III failed — was based on the small­er Phase II IMvig­or210 study.

Now the FDA will have to re­view whether the drug should stay on the mar­ket, af­ter Roche had al­ready launched an in­tense mar­ket­ing ef­fort on blad­der can­cer that quick­ly pushed sales past the $100 mil­lion mark last quar­ter. An­a­lysts have wide­ly tapped this ther­a­py as a fu­ture block­buster, worth bil­lions of dol­lars.

Sea­mus Fer­nan­dez, Leerink

“This puts the ex­ist­ing U.S. blad­der can­cer ap­proval in se­ri­ous doubt, and will al­so, of course, raise mar­ket con­cerns about Tecen­triq’s ef­fi­ca­cy in oth­er can­cer types,” Ke­pler Cheuvreux an­a­lyst David Evans wrote in a note to in­vestors, ac­cord­ing to a re­port in Reuters.

Count Sea­mus Fer­nan­dez at Leerink among the many an­a­lysts ad­just­ing to the un­ex­pect­ed. He not­ed:

This comes as a sur­prise to us, con­sid­er­ing MRK’s (MP) Keytru­da (pem­brolizum­ab; an­ti-PD-1) showed an OS ben­e­fit in its piv­otal Keynote-045 tri­al. As IMvig­or211 served as a con­fir­ma­to­ry study for Tecen­triq’s ac­cel­er­at­ed ap­proval for sec­ond-line (2L) blad­der can­cer, we as­sume that this will put this in­di­ca­tion at risk of be­ing re­moved from the la­bel. How­ev­er, the drug al­so has ac­cel­er­at­ed ap­proval for first-line (1L) pa­tients who are in­el­i­gi­ble for cis­platin based chemother­a­py and the con­fir­ma­to­ry tri­al for this pop­u­la­tion (IMvig­or130) is on­go­ing, with re­sults ex­pect­ed in 2019.

Ini­tial­ly ap­proved as a sec­ond-line treat­ment for blad­der can­cer, a first at the time, the Roche mar­ket­ing team hit the ground run­ning. Tecen­triq has been a cen­tral fea­ture of CEO Sev­erin Schwan’s strat­e­gy, help­ing him avoid ex­pen­sive M&A deals as he looks to the R&D group to de­liv­er new block­busters. Roche fol­lowed up just a few weeks ago with the ac­cel­er­at­ed OK as a front­line ther­a­py. The phar­ma gi­ant had no plans to look back now. It cer­tain­ly wasn’t ex­pect­ing the pos­si­bil­i­ty of a do-over.

Sev­erin Schwan, Roche CEO

Tecen­triq was the third PD-1/PD-L1 drug to reach the mar­ket, af­ter Mer­ck and Bris­tol-My­ers Squibb pi­o­neered the first ap­provals. Now there are 5 on the mar­ket, with Pfiz­er/Mer­ck KGaA and re­cent­ly As­traZeneca join­ing the pack. But while these drugs have of­fered new ways for sub­stan­tial num­bers of pa­tients to fight can­cer, they al­so con­tin­ue to oc­ca­sion­al­ly stun re­searchers with un­ex­pect­ed re­sults. Bris­tol-My­ers had to shake up its en­tire re­search or­ga­ni­za­tion af­ter a key fail­ure for Op­di­vo in lung can­cer last year de­railed their lead po­si­tion in the field.

This new fail­ure in blad­der can­cer, where sev­er­al check­points are now avail­able, rais­es ques­tions for every­one work­ing in check­point drug de­vel­op­ment. Co­in­ci­den­tal­ly, Mer­ck KGaA and Pfiz­er scored their own ap­proval to sell Baven­cio for blad­der can­cer on Tues­day. That OK was al­so con­di­tion­al on their fu­ture suc­cess with con­fir­ma­to­ry tri­als.

“While these re­sults are not what we had ex­pect­ed, we be­lieve that Tecen­triq will con­tin­ue to play an im­por­tant role in the treat­ment of peo­ple with ad­vanced blad­der can­cer,” said San­dra Horn­ing, chief med­ical of­fi­cer at Roche. “We are com­mit­ted to help­ing peo­ple with ad­vanced blad­der can­cer and will dis­cuss these da­ta with health au­thor­i­ties.”


Im­age: View of the Rhine Riv­er with the il­lu­mi­nat­ed Roche Tow­er, Basel, Switzer­land on April 24, 2017. Shut­ter­stock

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We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

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Deborah Dunsire. Lundbeck

Deb­o­rah Dun­sire is pay­ing $2B for a chance to leap di­rect­ly in­to a block­buster show­down with a few of the world's biggest phar­ma gi­ants

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Bright and early European time the company announced that it will pay up to about $2 billion to buy Alder, a little biotech that is far along the path in developing a quarterly IV formulation for a CGRP drug aimed at cutting back the number of crippling migraines patients experience each month.

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Lisa M. DeAngelis, MSKCC

MSK picks brain can­cer ex­pert Lisa DeAn­ge­lis as its next CMO — fol­low­ing José Basel­ga’s con­tro­ver­sial ex­it

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His replacement, who now will be in charge of MSK’s cutting-edge research work as well as the cancer care delivered by hundreds of practitioners, is Lisa M. DeAngelis. DeAngelis had been chair of the neurology department and co-founder of MSK’s brain tumor center and was moved in to the acting CMO role in the wake of Baselga’s departure.

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After establishing itself as one of the pioneer research centers in the world for CAR-T cancer therapies, creating new attack vehicles to eradicate cancer cells, a team at Penn Medicine has begun the tricky transition of using the basic technology for heart repair work.

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Tal Zaks. Moderna

The mR­NA uni­corn Mod­er­na has more ear­ly-stage hu­man da­ta it wants to show off — reach­ing new peaks in prov­ing the po­ten­tial

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The whole hand, of course, has yet to be dealt. And there’s no telling who gets to walk with a share of the pot. But any cards on display at this point — especially after being accused of keeping its deck under lock and key — will attract plenty of attention from some very wary, and wired, observers.

“In terms of the complexity and unmet need,” says Tal Zaks, the chief medical officer, “this is peak for what we’ve accomplished.”

Moderna has two Phase I studies it wants to talk about now.

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Traditionally, peanut allergies are managed by avoidance, but the threat of accidental exposure cannot be nullified. Some allergists have devised a way to dose patients off-label with peanut protein derived from supermarket products to wean them off their allergies. But the idea behind Aimmune’s product was to standardize the peanut protein, and track the process of desensitization — so when accidental exposure in the real world invariably occurs, patients are less likely to experience a life-threatening allergic reaction.

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Adverum, on Wednesday, unveiled 24-week data from the OPTIC trial of its experimental therapy, ADVM-022, in six patients who have been administered with one dose of the therapy. On average, patients in the trial had severe disease with an average of 6.2 anti-VEGF injections in the eight months prior to screening and an average annualized injection frequency of 9.3 injections.

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Too often, Alex Arfaei arrived too late. 

An analyst at BMO Capital Markets, he’d meet with biotech or pharmaceutical heads for their IPO or secondary funding and his brain, trained on a biology degree and six years at Merck and Endo, would spring with questions: Why this biomarker? Why this design? Why not this endpoint? Not that he could do anything about it. These execs were coming for clinical money; their decisions had been made and finalized long ago.