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

Image courtesy of The Janssen Pharmaceutical Companies of Johnson & Johnson.

Pro­tect­ing the glob­al phar­ma­ceu­ti­cal in­no­va­tion ecosys­tem – what’s at stake?

We are living in a new era of healthcare that is rapidly advancing progress impacting patient outcomes and experiences. We’ve seen a remarkable pace of transformational innovation, applied research, and advanced clinical development over the last decade.

Despite this tremendous progress, there is much more work to be done, and patients are counting on us – now more than ever – to continue that momentum. At the heart of our industry is a focus on developing and delivering medicines for some of the world’s most challenging diseases, including those that have few or no effective treatments today.

Mi­rati’s drug sitra­va­tinib flops PhI­II in com­bo with Op­di­vo for cer­tain lung can­cer

Mirati Therapeutics’ path to a second drug approval will likely have to wait. The San Diego biotech company said Wednesday that its investigational lung cancer drug failed a Phase III trial testing it in combination with Bristol Myers Squibb’s Opdivo.

The drug, sitravatinib, and Opdivo weren’t better than the chemo drug docetaxel at keeping patients alive, Mirati said in a press release. The spectrum-selective kinase inhibitor missed the primary goal of overall survival in patients with second- or third-line advanced non-squamous, non-small cell lung cancer.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,300+ biopharma pros reading Endpoints daily — and it's free.

End­points 20(+2) un­der 40, 2023; Bio­phar­ma's high­est-paid CEOs; N-of-1 CRISPR sto­ry goes on af­ter tragedy; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

We will be off Monday in observance of Memorial Day — and when we get back, it will be a straight march to ASCO, BIO and more. Enjoy the (long) weekend!

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,300+ biopharma pros reading Endpoints daily — and it's free.

Rich Horgan (R) with his late brother, Terry

Rich Hor­gan spear­head­ed a gene ther­a­py for his broth­er. The tri­al end­ed in tragedy, but the work con­tin­ues for more pa­tients

Rich Horgan’s quest to create a custom gene therapy for his brother, Terry, ended in tragedy. But Horgan doesn’t believe it’s the end of the story.

Terry, a 27-year-old patient with Duchenne muscular dystrophy, died last October just eight days after receiving the therapy in a clinical trial in which he was the only participant. The case raised questions about the safety of certain gene therapies and what would happen to other drug programs under a nonprofit that Horgan created, called Cure Rare Disease.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,300+ biopharma pros reading Endpoints daily — and it's free.

Bio­phar­ma's 20 high­est-paid CEOs of 2022, each bring­ing in $20M+ pay­days

Even in a down year for much of the biopharma market, 20 CEOs brought in pay packages valued at more than $20 million, an Endpoints News analysis found.

Endpoints collected data on more than 350 CEO compensation packages, covering a wide range of pharma, biotech, and life sciences companies. All told, the 20 largest earners made over $725 million in 2022 — an average package of $36.4 million. Three brought in paydays over $50 million, and one CEO broke the $100 million mark.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,300+ biopharma pros reading Endpoints daily — and it's free.

The 20(+2) un­der 40: Your guide to the next gen­er­a­tion of biotech lead­ers

This year’s list of 20 biotech leaders under the age of 40 includes a huge range of ambitions. Some of our honorees are planning to create the next big drug giant. Others are pushing the bounds of AI. One is working to revolutionize TB testing. All are compelling talents who are still young in age, but already far along in achievement.

And, as in years past, we went over. The 20 are actually 22 because of two double profiles that reflect how important teamwork is in the industry. As one of our honorees, Joe Illingworth of DJS Antibodies, told me in our interview, “It takes a village to raise a biotech.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,300+ biopharma pros reading Endpoints daily — and it's free.

Teresa Bitetti, Takeda's president of the global oncology business unit

Take­da wins pri­or­i­ty re­view for $400M col­orec­tal can­cer drug, li­censed from Hutchmed in Jan­u­ary

Takeda and Hutchmed scored a priority review Thursday afternoon for a colorectal cancer drug, the companies announced.

The experimental drug in question is fruquintinib, previously approved in China in 2018 to treat metastatic colorectal cancer. Takeda and Hutchmed are aiming to bring fruquintinib to the US and other countries outside China in the same indication, and the FDA set its decision date for Nov. 30 of this year.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,300+ biopharma pros reading Endpoints daily — and it's free.

David Ricks, Eli Lilly CEO (Carolyn Kaster/AP Images)

Lil­ly gears up trio of PhI­II tri­als for its oral GLP-1 amid No­vo Nordisk, Pfiz­er com­pe­ti­tion

As Novo Nordisk and Pfizer disclose some data on their oral weight loss drugs in Phase III and II, respectively, Eli Lilly is beefing up its stance in the obesity field with three late-stage clinical trials of its next-generation GLP-1 agonist orforglipron.

The moves, disclosed in updates to the federal clinical trials database this week, put the Indianapolis drugmaker ahead of Pfizer, whose science chief has said the company will “cherry-pick” which of its mid-stage candidates to take deeper into the clinic after data late this year or early next.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,300+ biopharma pros reading Endpoints daily — and it's free.

Douglas Love, Annexon CEO

An­nex­on’s GA drug miss­es on pri­ma­ry goal but win on vi­su­al acu­ity will be fo­cus of planned late-stage tri­al

Annexon’s complement inhibitor didn’t prove better than sham at reducing lesion growth in a leading cause of blindness, but the biotech still plans to move forward on the back of secondary endpoints showing visual acuity preservation, which will “certainly” be the primary goal in a late-stage trial to be discussed shortly with the FDA, CEO Douglas Love told Endpoints News. 

The California biotech’s ANX007 was not statistically significant compared to pooled sham, the comparator, at 12 months in patients with geographic atrophy, per a Wednesday presentation. In every-month dosing, the GA lesion area changed about 6.2% from baseline (p=0.526) and 1.3% (p=0.896) in the every-other-month group. In a March note, Jefferies analyst Suji Jeong said a reduction of 20% to 30% would be “encouraging.”

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.