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

Take­da swoops in to buy lit­tle biotech part­ner and its celi­ac drug poised to 'change stan­dard of care'

Having spent three years carefully grooming PvP Biologics and its drug for celiac disease, Takeda is happy enough with the proof-of-concept data to buy it all.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 73,100+ biopharma pros reading Endpoints daily — and it's free.

Grow­ing ac­cep­tance of ac­cel­er­at­ed path­ways for nov­el treat­ments: but does reg­u­la­to­ry ap­proval lead to com­mer­cial suc­cess?

By Mwango Kashoki, MD, MPH, Vice President-Technical, and Richard Macaulay, Senior Director, of Parexel Regulatory & Access

In recent years, we’ve seen a significant uptake in the use of regulatory options by companies looking to accelerate the journey of life-saving drugs to market. In 2018, 73% of the novel drugs approved by the U.S. Federal Drug Administration (FDA) were designated under one or more expedited development program categories (Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval).ᶦ

Mi­cro­bio­me Q&A: New study maps the vagi­na's 'op­ti­mal mi­cro­bio­ta' — and its im­pli­ca­tions for bio­phar­ma

The widely-held notion that the “optimal” vaginal microbiota is dominated by one strain of lactic-acid producing bacteria has now been challenged in a new paper, published in Nature Communications on Wednesday, which used advanced gene sequencing methods to map out the most comprehensive gene catalog of the human vaginal microbiome.

Things have changed in the more than 50 years since the concept of vaginal microbiota transplants was proposed and subsequently tainted by a Texas-based gynecologist who transplanted the vaginal fluid of women who had bacterial vaginosis into healthy females, suspecting he had isolated the bacteria responsible for the condition.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 73,100+ biopharma pros reading Endpoints daily — and it's free.

Fol­low­ing US, Chi­na hos­pi­tal ef­forts, Gilead plots its own PhI­II tri­als for close­ly watched Covid-19 drug

Gilead is launching its own Phase III trials of remdesivir, the repurposed antiviral that a WHO official called the “one drug right now we think may have real efficacy” against Covid-19 as the novel coronavirus originating from Wuhan, China ravages the world.

Announced just a day after the NIH and the University of Nebraska Medical Center registered their US-based trial online, Gilead’s program will comprise two studies enrolling around 1,000 patients beginning in March. They will recruit primarily in Asian countries but will also include patients from other locations with “high numbers of diagnosed cases,” the company said.

Bio­gen touts new ev­i­dence from the gene ther­a­py com­pa­ny it wa­gered $800M on

A year ago, Biogen made a big bet on a small gene therapy company. Now they have new evidence one of their therapies could work.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 73,100+ biopharma pros reading Endpoints daily — and it's free.

Anthony Fauci (AP Images)

UP­DAT­ED: NIH-part­nered Mod­er­na ships off its PhI-ready coro­n­avirus vac­cine can­di­date to a sea of un­cer­tain­ty

Off it goes.

Moderna has shipped the first batch of its mRNA vaccine against SARS-CoV-2 from its manufacturing facility in Norwood, Massachusetts, to the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, for a pioneering Phase I study.

It’s a hectic race against time. In the 42 days since Moderna selected the sequence they would use to develop their vaccine — a record time, no less — the number of confirmed cases around the world has surged astronomically from a few dozen to over 80,000, per WHO and Johns Hopkins estimates.

The candidate that they came up with, mRNA-1273, encodes for a prefusion stabilized form of the spike protein, which gives the virus its crown shape and plays a key role in transmission. The Coalition for Epidemic Preparedness Innovations, the Oslo-based group better known as CEPI, funded the manufacture of this batch.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 73,100+ biopharma pros reading Endpoints daily — and it's free.

In at least one life-sci hub, gen­der and di­ver­si­ty ini­tia­tives haven’t made a dent

Gender and racial diversity at the top of UK life science companies has hardly budged over the last seven years despite repeated advocacy efforts, according to a new report.

The report, from the recruiting firm Liftstream, found that 14.8% of directors on life sciences boards were women and 21.1% of top executives were women. That’s a modest bump from the 9.8% of directors and 18.1% of executives Liftstream identified in their last report from 2014. The percentage of women CEOs moved from 8% to 9.8%.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 73,100+ biopharma pros reading Endpoints daily — and it's free.

Will a 'risk-of­f' mind­set has­ten cell ther­a­py M&A? Io­vance surges on buy­out chat­ter

Is it time for some cell therapy M&A?

Investors of Iovance Biotherapeutics certainly thought so, sending its stock $IOVA up as much as 40% after Bloomberg reported that the cancer-focused biotech is talking to potential buyers.

While 2019 saw a number of high-profile gene therapy company takeovers — led by Roche’s $4.3 billion bid of Spark as Astellas went for Audentes, Biogen snapped up Nightstar and Vertex absorbed Exonics — large players appeared to prefer partnering on the cell therapy front, particularly when it comes to cancer. Hal Barron put his weight behind Rick Klausner’s startup as he rebuilt GlaxoSmithKline’s cancer pipeline. Takeda turned to MD Anderson to license their natural killer cell therapy.

One less ri­val for Im­muno­vant, as Alex­ion aban­dons FcRn in­hibitor

Less than one year after Alexion parted with $25 million upfront to secure access to a second anti-FcRn asset, it is abandoning the experimental drug. The discontinuation, disclosed at the SVB Leerink Global Healthcare Conference in New York during a fireside chat, bodes well for rival Immunovant.

The drug (ABY-039), partnered for development with Sweden’s Affibody, was forsaken on the basis of early-stage data that was not viewed favorably, Baird and SVB Leerink analysts noted.