Mer­ck pulls the plug on a study eval­u­at­ing block­buster Keytru­da with Yer­voy for NSCLC

About a month ago, up­on tout­ing new on­col­o­gy da­ta, Mer­ck reaf­firmed its com­mit­ment to ex­plor­ing new Keytru­da com­bi­na­tions for lung can­cer pa­tients. The Big Phar­ma has now pulled the plug on one of those com­bi­na­tions, af­ter in­ter­im da­ta showed an in­creased risk and no re­ward.

An in­de­pen­dent Da­ta Mon­i­tor­ing Com­mit­tee urged Mer­ck to end a Phase III tri­al eval­u­at­ing cash cow Keytru­da — which brought in $11.1 bil­lion last year — and Bris­tol My­ers Squibb’s Yer­voy (ip­il­i­mum­ab) in PD-L1 pos­i­tive metasta­t­ic non-small cell lung can­cer (NSCLC) pa­tients. In an in­ter­im analy­sis, the com­bi­na­tion showed no in­cre­men­tal ben­e­fit in over­all sur­vival (OS) or pro­gres­sion-free sur­vival (PFS), the study’s two pri­ma­ry end­points.

To make mat­ters worse, the com­bo was linked to a high­er in­ci­dence of side ef­fects, in­clud­ing se­ri­ous ad­verse events and ad­verse events lead­ing to “dis­con­tin­u­a­tion or death,” com­pared to the Keytru­da monother­a­py, ac­cord­ing to Mer­ck.

A to­tal of 568 pa­tients re­ceived ei­ther 200 mg of Keytru­da in­tra­venous­ly once every three weeks for up to 35 cy­cles and 1 mg/kg IV of Yer­voy once every six weeks for up to 18 cy­cles, or the same amount of Keytru­da with a place­bo. The full da­ta are com­ing at a fu­ture sci­en­tif­ic con­gress, and will be re­port­ed to reg­u­la­tors, the com­pa­ny an­nounced.

Roy Baynes

“It is very clear that in this study, the ad­di­tion of ip­il­i­mum­ab did not add clin­i­cal ben­e­fit but did add tox­i­c­i­ty. Keytru­da monother­a­py re­mains a stan­dard of care for the treat­ment of cer­tain pa­tients with metasta­t­ic non-small cell lung can­cer whose tu­mors ex­press PD-L1,” Roy Baynes, CMO and head of glob­al clin­i­cal de­vel­op­ment at Mer­ck Re­search Lab­o­ra­to­ries, said in a state­ment.

Bris­tol My­ers Squibb didn’t take the jab light­ly, and fol­lowed up with End­points News to em­pha­size that its own PD-1, Op­di­vo, pairs quite well with Yer­voy.

“Check­Mate -227, Check­Mate -9LA and Keynote -598 are all dif­fer­ent tri­als, with dif­fer­ent pa­tient pop­u­la­tions, com­para­tors, end­points and du­ra­tions of fol­low-up. For ex­am­ple, Check­Mate -227 and Check­Mate -9LA en­rolled pa­tients across PD-L1 ex­pres­sion lev­els and his­tolo­gies. Keynote -598 on­ly en­rolled pa­tients with PD-L1 ex­pres­sion ≥50%,” a spokesper­son said.

While Yer­voy has been ap­proved with an an­ti-PD-1 ther­a­py in some in­di­ca­tions, most stud­ies sup­port­ing those ap­provals didn’t com­pare the com­bi­na­tion di­rect­ly to the an­ti-PD-1 monother­a­py, ac­cord­ing to Mer­ck. Back in May, Op­di­vo and Yer­voy got a land­mark NSCLC ap­proval ap­proval for PD-L1 pos­i­tive pa­tients — but the tri­al com­pared the com­bi­na­tion to treat­ment with plat­inum-dou­blet chemother­a­py. Days lat­er, the com­bo was al­so ap­proved in com­bi­na­tion with a lim­it­ed course of chemother­a­py.

In Check­Mate-915, re­searchers did eval­u­ate Op­di­vo and Yer­voy against Op­di­vo alone in ad­ju­vant melanoma pa­tients. How­ev­er, they found that the com­bi­na­tion didn’t achieve a sig­nif­i­cant im­prove­ment in re­cur­rence-free sur­vival (RFS) in the all-com­er pop­u­la­tion.

“We re­main com­mit­ted to con­tin­ued re­search in melanoma, both to fur­ther un­der­stand the po­ten­tial ben­e­fit of Yer­voy in com­bi­na­tion with Op­di­vo to treat high-risk melanoma pa­tients in the ear­li­er stages of dis­ease, as well as to study ad­di­tion­al nov­el com­bi­na­tions in var­i­ous set­tings,” Bris­tol My­ers Squibb VP and head of on­col­o­gy clin­i­cal de­vel­op­ment Sabine Maier said in a state­ment at the time.

Keytru­da is al­ready ap­proved to treat a va­ri­ety of can­cers aside from NSCLC, in­clud­ing small cell lung can­cer, melanoma, head and neck squa­mous cell can­cer, and Hodgkin lym­phoma, to name a few. Yer­voy is ap­proved for un­re­sectable or metasta­t­ic melanoma, and in com­bi­na­tion with Op­di­vo for sev­er­al can­cers, in­clud­ing NSCLC, mis­match re­pair de­fi­cient metasta­t­ic col­orec­tal can­cer, ad­vanced re­nal cell car­ci­no­ma and he­pa­to­cel­lu­lar car­ci­no­ma.

Back in May, Roche’s Tecen­triq got FDA ap­proval to treat new­ly di­ag­nosed, metasta­t­ic NSCLC pa­tients with­out EGFR or ALK mu­ta­tions whose tu­mors have high PD-L1 ex­pres­sion. “By virtue of be­ing late to mar­ket, Tecen­triq monother­a­py (IM­POW­ER110) has lit­tle chance of gain­ing sig­nif­i­cant share in 1L NSCLC de­spite post­ing OS sim­i­lar to Keytru­da in PD-L1 high pa­tients,” Cowen an­a­lyst Steve Scala wrote to in­vestors that month.

In­side Track: Be­hind the Scenes of a Ma­jor Biotech SPAC

Dr. David Hung and Michelle Doig are no strangers to the SPAC phenomenon. As Founder and CEO of Nuvation Bio, a biotech company tackling some of the greatest unmet needs in oncology, Dr. Hung recently took the company public in one of this year’s biggest SPAC related deals. And as Partner at Omega Funds, Doig not only led and syndicated Nuvation Bio’s Series A, but is now also President of the newly formed, Omega-sponsored, Omega Alpha SPAC (Nasdaq: OMEG; oversubscribed $138m IPO priced January 6, 2021).

Aduhelm OK 'bit­ter­sweet' for ALS ad­vo­cates; Con­trast­ing Covid-19 vac­cine read­outs; GSK joins TIG­IT bat­tle; 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.

With the busiest days of June now behind us, we’re starting to think seriously about the second half of the year. In August, we have scheduled a special report where Endpoints will compile a list of the 20 most influential R&D executives in biopharma. Know a luminary who should definitely be included? Nominate them now.

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Who are the lu­mi­nar­ies dri­ving the biggest ad­vances in bio­phar­ma R&D? End­points News is ask­ing for your nom­i­na­tions for a spe­cial re­port

In biopharma, driving a drug to market is the ultimate goal — but none of that happens without a strong research and development program. At the most successful companies, those R&D efforts are spearheaded by true innovators in the field who are always looking for that next novel mechanism of action or breakthrough safety profile.

Now, Endpoints News is asking you to tell us who those guiding lights are.

Leen Kawas, Athira CEO

Biotech founder placed on leave as $400M Alzheimer's start­up idea comes un­der scruti­ny

Athira Pharma, the Alzheimer’s biotech that emerged out of obscurity last year and raised nearly $400 million for a dark-horse approach to treating neurodegeneration, has found itself in sudden turmoil.

On Tuesday evening, the company released a terse statement announcing that CEO and founder Leen Kawas had been placed on administrative leave while an independent review board investigated “actions stemming” from her doctoral research at Washington State University. Mark Litton, who joined the company as COO two years ago, will take over day-to-day operations, they said.

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Bris­tol My­ers breaks the bank on Ei­sai's fo­late re­cep­tor ADC drug, lay­ing out more than $3B+ for rights

For years, innovation in oncology has been a crapshoot with Big Pharma — the whales at the table — dropping the big bucks for the key to the next generation of tumor fighters. Bristol Myers Squibb hasn’t exactly made a name for being an innovator in the space, but that doesn’t mean it won’t splash in when it sees a potential winner.

Now, with a massive check in hand, the drugmaker is willing to put its intuition to the test.

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Michael Chambers (L) and John Ballantyne

Dana­her strikes deal to buy boom­ing next-gen man­u­fac­tur­er Alde­vron for $9.6B

Life sciences conglomerate Danaher Corp. $DHR has struck a deal to buy the fast-growing Aldevron, one of the world’s top manufacturers of hotly sought-after plasmid DNA, mRNA and recombinant proteins for the burgeoning world of vaccine and drugmakers pushing some game-changing technologies.

Buyout talks set the stage for Danaher to settle on a $9.6 billion cash pact to acquire the private Fargo, ND-based company — a key supplier for a disruptive new Covid vaccine as well as a host of gene and cell therapy and CRISPR gene editing players — founded by Michael Chambers and CSO John Ballantyne as a crew of 2 back in 1998.

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Jeff Albers, Blueprint CEO

Blue­print Med­i­cines nabs 4th ap­proval in bid to­ward prof­itabil­i­ty

Blueprint Medicines’ push to profitability continues.

On Wednesday, the Cambridge biotech announced the FDA approved its longtime lead drug, Ayvakit, for advanced systemic mastocytosis, a group of debilitating rare diseases where one type of immune cell — mast cells — builds up uncontrollably in a particular organ. The decision came on the heels of Phase III trials showing that more than half of late-stage patients who received the drug responded to it and did so for just over three years.

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Franz-Werner Haas, CureVac CEO (Christoph Schmidt/picture-alliance/dpa/AP Images)

UP­DAT­ED: Cure­Vac blames vari­ants as a close­ly-watched Covid vac­cine goes down in flames, fail­ing piv­otal study with woe­ful da­ta

CureVac was widely expected to come in with a late but likely late-stage winner in the race to develop new vaccines for the Covid-19 pandemic. Instead, late Wednesday, the German biotech said their mRNA candidate CVnCoV flat failed a pivotal trial — quashing any hopes for a quick entry in the blockbuster field and gutting their share price.

CVnCoV demonstrated an interim vaccine efficacy of 47% against COVID-19 disease of any severity and did not meet prespecified statistical success criteria. Initial analyses suggest age and strain dependent efficacy.

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Al Sandrock, Biogen R&D chief (Biogen via YouTube)

Days af­ter con­tro­ver­sy greet­ed Bio­gen's block­buster Alzheimer's OK, the big biotech con­cedes a set­back on the tau front

Just days after triggering a maelstrom of controversy with their decision to launch an unproven Alzheimer’s drug with a $56,000 price, Biogen $BIIB is back with the latest data on its mid-stage tau drug.

And it’s not good.

The big biotech says that gosuranemab — targeted at tau, the second leading drug target in Alzheimer’s — flat failed its Phase II and will now be taken out and dumped in the mass grave for all but one other Alzheimer’s drug in the past generation.

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