Pfiz­er, Mer­ck KGaA run in­to a se­vere set­back as PD-L1 drug Baven­cio fails in PhI­II gas­tric can­cer study

Pfiz­er $PFE and its part­ner Mer­ck KGaA have run in­to a dead end in their race to ex­pand the mar­ket for their PD-L1 check­point Baven­cio (avelum­ab). Re­searchers to­day con­ced­ed that the check­point — one of 5 now scram­bling to ex­pand their mar­ket turf in the mega-block­buster glob­al on­col­o­gy busi­ness — failed to sig­nif­i­cant­ly im­prove over­all sur­vival for ad­vanced gas­tric can­cer pa­tients com­pared to best stan­dard of care.

We won’t see the da­ta un­til a lat­er sci­en­tif­ic con­fer­ence to be de­cid­ed on, but the JAVELIN Gas­tric 300 flop will put a def­i­nite hitch in their plans to ex­pand sales for a key drug in both com­pa­nies’ pipelines.

Lu­ciano Ros­set­ti, Mer­ck KGaA

Mer­ck KGaA R&D chief Lu­ciano Ros­set­ti put the fail­ure down to their de­ci­sion to test the drug against cur­rent­ly used chemo rather than a place­bo. He not­ed:

“Gas­tric can­cer in the third-line set­ting is a par­tic­u­lar­ly hard-to-treat and het­ero­ge­neous dis­ease, and im­por­tant­ly, this was the first tri­al con­duct­ed with a check­point in­hibitor com­pared to an ac­tive chemother­a­py com­para­tor rather than place­bo in a glob­al pa­tient pop­u­la­tion.”

The tri­al en­rolled 371 pa­tients from 147 sites in Asia, Aus­tralia, Eu­rope, North Amer­i­ca and South Amer­i­ca. Gas­tric can­cer counts as the third most com­mon type of can­cer killer.

Their mis­for­tune is US Mer­ck’s gain, as well as Bris­tol-My­ers Squibb’s, which both earned third-line ap­provals af­ter test­ing their drugs against a place­bo.

Mer­ck gained an ac­cel­er­at­ed OK from the FDA two months ago to use Keytru­da, a PD-1 check­point, against ad­vanced gas­tric can­cer af­ter lay­ing out mar­gin­al­ly suc­cess­ful re­sponse rates for pa­tients whose tu­mors hit the mark on PD-L1 ex­pres­sion. And af­ter look­ing over the da­ta on over­all sur­vival for both ap­proved ther­a­pies, Uber Raf­fat at Ever­core ISI con­clud­ed that Pfiz­er and Mer­ck KGaA faced tough odds from the start.

And the fail­ure rais­es an­oth­er is­sue, he says:

Im­me­di­ate­ly makes you won­der: is avelum­ab in­fe­ri­or on ef­fi­ca­cy?  And does this tie in­to the broad­er PDL1 vs PD1 de­bate?

That de­bate cen­ters on a heat­ed dis­cus­sion of whether PD-L1 is in­her­ent­ly weak­er than PD-1, so you can ex­pect to hear lots more about it.

This set­back for Pfiz­er and Mer­ck KGaA al­so un­der­scores the se­ries of stun­ning sur­pris­es that con­tin­ues to ad­vance some play­ers while oth­ers are held back. Check­points, which re­moves a brake on an im­mune sys­tem re­sponse to can­cer cells, are fast en­ter­ing the stan­dard of care in a wide range of on­col­o­gy mar­kets, both as a so­lo ther­a­py as well as in com­bi­na­tion. And there’s been a fren­zied race to field new check­points, as we high­light in this re­cent piece not­ing 50 PD-1/L1 ther­a­pies in the clin­ic and 114 more in pre­clin­i­cal de­vel­op­ment.

Still in the pipeline is a Phase III study — JAVELIN Gas­tric 100 — which is test­ing the check­point as a front­line ther­a­py for gas­tric can­cer.

Com­mu­ni­cat­ing the val­ue of pre­ci­sion med­i­cine

By Natasha Cowan, Content Marketing Manager at Blue Latitude Health.
Many stakeholders are confused by novel precision medicines, including patients and healthcare professionals. So, how can industry help them to navigate this complexity?

Precision medicine represents a new paradigm in healthcare. It embodies the shift from treating many patients with the same therapy, to having the tools to identify the best treatment for every patient.

Spe­cial re­port: Twen­ty ex­tra­or­di­nary women in bio­phar­ma R&D who worked their way to the top

What differentiates a woman leader in biopharma R&D from a man?

Not much, except there are fewer of them in senior posts. Data suggest women are not more risk-averse, family-oriented or less confident than their male counterparts — indeed the differences between the two sexes are negligible. But a glance at the top R&D positions in Big Pharma leaves little doubt that upward migration in the executive ranks of biopharma R&D is tough.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,300+ biopharma pros reading Endpoints daily — and it's free.

GSK's asth­ma bi­o­log­ic Nu­cala scores in rare blood dis­or­der study

GlaxoSmithKline’s asthma drug Nucala, which received a resounding FDA rejection for use in chronic obstructive pulmonary disease (COPD) last year, has shown promise in a rare blood disorder.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,300+ biopharma pros reading Endpoints daily — and it's free.

Mer­ck buys a fledg­ling neu­rode­gen­er­a­tive biotech spawned by an old GSK dis­cov­ery al­liance. What’s up with that?

Avalon Ventures chief Jay Lichter has a well-known yen for drug development programs picked up in academia. And what he found in Haoxing Xu’s lab at the University of Michigan pricked his interest enough to launch one of his umbrella biotechs in San Diego.
Xu’s work laid the foundation for Avalon to launch Calporta, which has been working on finding small molecule agonists of TRPML1 (transient receptor potential cation channel, mucolipin subfamily, member 1) for lysosomal storage disorders. And that pathway, they believe, points to new approaches on major market neurodegenerative diseases like Parkinson’s, ALS and Alzheimer’s.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,300+ biopharma pros reading Endpoints daily — and it's free.

FDA slaps a hold on an AML tri­al as Mark­er scraps a fail­ing ovar­i­an can­cer pro­gram, sink­ing shares

The FDA has placed a hold on a Phase II AML trial from the small immuno-oncology biotech Marker Therapeutics. Marker disclosed the issue two weeks after responding to FDA concerns, adding it to the Q3 release Tuesday. The company also announced it was scrapping a Phase II ovarian cancer program it determined was unlikely to succeed.

The agency’s concern centers around two reagents used in manufacturing for their trial for acute myeloid leukemia patients who have received a stem cell transplant. The reagents are from third parties and not present in the final product, Marker said.

Eli Lil­ly-backed biotech grabs $100M to dis­patch an­ti­body-oligonu­cleotide con­ju­gates af­ter mus­cu­lar dy­s­tro­phy

Hold up your hand. Make a fist. Now open it. And again.

If you can do it fully and with ease, then the proteins in your hand are likely working properly. If you can’t then they may not be. In people with myotonic muscular dystrophy, something more atomic is going on.

In those folks, the problem is RNA. Certain base pairs repeat far beyond normal, up to 11,000 superfluous letters in some cases. The extended strands form “clumps.” Proteins misform and can’t function properly. They often allow one movement but not the reverse, a condition called myotonia that gives the dystrophy its name.

As­traZeneca sets stage for mar­ket­ing ap­pli­ca­tion with promis­ing piv­otal lu­pus drug da­ta

After fumbling in its first late-stage lupus study, AstraZeneca disclosed that a second pivotal trial testing its experimental drug, anifrolumab, had met the main goal, in August. Earlier this week, the British drugmaker broke out the numbers from its successful study.

Last year, anifrolumab failed to meet the main goal of diminishing disease activity in the 460-patient TULIP I study, a 52-week trial that tested two doses of the drug versus a placebo. But in the 373-patient TULIP II study, the higher dose (300 mg) was compared to patients given a placebo — patients in both arms were on baseline standard care.

FDA Vas­cepa re­view spot­lights new safe­ty sig­nals, pos­si­ble min­er­al oil spoil­er as Amarin hunts a block­buster ap­proval

An in-house FDA review of Amarin’s Vascepa raises a set of hurdles the biotech will have to clear if the biotech expects to get the long-awaited FDA approval that could set it on a path to superstar status. But it appears that Amarin has survived another potential setback without introducing a major new threat to its prospects.

The stakes don’t get much higher, with analysts saying a win this week for Amarin could lead to billions in new sales — provided the agency stamps it with an OK. And investors liked what they say in the FDA review this morning, bumping the stock $AMRN 17%.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,300+ biopharma pros reading Endpoints daily — and it's free.

FDA puts Sol­id Bio’s lead gene ther­a­py pro­gram on hold — again — af­ter an­oth­er pa­tient is hurt by SGT-001

Solid Biosciences continues to be plagued by safety issues.

Close to 18 months after the gene therapy biotech was able to quickly shed an FDA hold on their lead Duchenne muscular dystrophy program for SGT-001, regulators have stepped back in to force another halt after another patient was hit hard by a set of serious adverse events remarkably similar to the first set.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,300+ biopharma pros reading Endpoints daily — and it's free.