Keytru­da PhI­II fail­ure in gas­tric can­cer blights Mer­ck­'s quest for front­line dom­i­nance

A year and a half af­ter scor­ing an ap­proval to use Keytru­da in third-line gas­tric can­cer, Mer­ck has run in­to a wall try­ing to ap­ply the PD-1 star in the front­line set­ting.

In an up­date for the KEYNOTE-062, the com­pa­ny $MRK dis­closed that Keytru­da as a monother­a­py proved non-in­fe­ri­or to chemother­a­py — the cur­rent stan­dard of care for ad­vanced gas­tric or gas­troe­sophageal junc­tion ade­no­car­ci­no­ma — in over­all sur­vival. In com­bi­na­tion, though, Keytru­da plus chemo was not found to be su­pe­ri­or for ei­ther OS or pro­gres­sion-free sur­vival com­pared with chemo alone. That like­ly meant more miss­es than hits in the pri­ma­ry end­points, list­ed as PFS and OS on clin­i­cal­tri­

As a spokesper­son ex­plained:

Based on the pre-spec­i­fied sta­tis­ti­cal analy­sis plan, su­pe­ri­or­i­ty test­ing for OS in the KEYTRU­DA monother­a­py group was con­duct­ed, how­ev­er as an­nounced, the fi­nal analy­sis showed that KEYTRU­DA monother­a­py was non-in­fe­ri­or, not su­pe­ri­or, to the chemother­a­py arm in pa­tients whose tu­mors were CPS ≥1. For KEYNOTE-062, it made sense to test for non­in­fe­ri­or­i­ty in the event that KEYTRU­DA monother­a­py had com­pa­ra­ble ef­fi­ca­cy as chemother­a­py with a po­ten­tial­ly fa­vor­able safe­ty and tol­er­a­bil­i­ty pro­file.

Roy Baynes

Mer­ck went ahead with the Phase III tri­al de­spite a flop in the sec­ond-line set­ting of the same in­di­ca­tion in 2017. Grant­ed, the drug had pos­i­tive third-line da­ta go­ing for it in a tough dis­ease where Pfiz­er and Mer­ck KGaA’s PD-L1 drug Baven­cio failed.

All pa­tients in the tri­al had tu­mors that ex­press PD-L1. In­ves­ti­ga­tors did not tease out any dif­fer­ences be­tween those with a high com­bined pos­i­tive score (CPS ≥10) and those with low CPS, of 1 or above.

“Gas­tric can­cer is his­tor­i­cal­ly dif­fi­cult to treat, and un­for­tu­nate­ly con­tin­ues to be as­so­ci­at­ed with high mor­tal­i­ty rates in many coun­tries, par­tic­u­lar­ly in the metasta­t­ic stage,” said Roy Baynes, Mer­ck’s head of glob­al de­vel­op­ment, in a state­ment.

The brief state­ment al­so didn’t cov­er any of the sec­ondary end­points, in­clud­ing over­all re­sponse rate, du­ra­tion of re­sponse, qual­i­ty of life and a gas­tric can­cer score.

Mer­ck says it plans to dis­cuss the fi­nal analy­sis with the FDA, as well as oth­er on­go­ing gas­tric stud­ies that might serve as con­fir­ma­to­ry tri­als, in­clud­ing KEYNOTE-811 and KEYNOTE-859. Then there’s the Phase III KEYNOTE-585 to watch, where Keytru­da in com­bi­na­tion with chemother­a­py is test­ed in a neoad­ju­vant/ad­ju­vant set­ting.

Nick Leschly via Getty

UP­DAT­ED: Blue­bird shares sink as an­a­lysts puz­zle out $1.8M stick­er shock and an un­ex­pect­ed de­lay

Blue­bird bio $BLUE has un­veiled its price for the new­ly ap­proved gene ther­a­py Zyn­te­glo (Lenti­Glo­bin), which came as a big sur­prise. And it wasn’t the on­ly un­ex­pect­ed twist in to­day’s sto­ry.

With some an­a­lysts bet­ting on a $900,000 price for the β-tha­lassemia treat­ment in Eu­rope, where reg­u­la­tors pro­vid­ed a con­di­tion­al ear­ly OK, blue­bird CEO Nick Leschly said Fri­day morn­ing that the pa­tients who are suc­cess­ful­ly treat­ed with their drug over 5 years will be charged twice that — $1.8 mil­lion — on the con­ti­nent. That makes this drug the sec­ond most ex­pen­sive ther­a­py on the plan­et, just be­hind No­var­tis’ new­ly ap­proved Zol­gens­ma at $2.1 mil­lion, with an­a­lysts still wait­ing to see what kind of pre­mi­um can be had in the US.


Glob­al Blood Ther­a­peu­tics poised to sub­mit ap­pli­ca­tion for ac­cel­er­at­ed ap­proval, with new piv­otal da­ta on its sick­le cell dis­ease drug

Global Blood Therapeutics is set to submit an application for accelerated approval in the second-half of this year, after unveiling fresh data from a late-stage trial that showed just over half the patients given the highest dose of its experimental sickle cell disease drug experienced a statistically significant improvement in oxygen-wielding hemoglobin, meeting the study's main goal.

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Gene ther­a­pies seize the top of the list of the most ex­pen­sive drugs on the plan­et — and that trend has just be­gun

Anyone looking for a few simple reasons why the gene therapy field has caught fire with the pharma giants need only look at the new list of the 10 most expensive therapies from GoodRx.

Two recently approved gene therapies sit atop this list, with Novartis’ Zolgensma crowned the king of the priciest drugs at $2.1 million. Right below is Luxturna, the $850,000 pioneer from Spark, which Roche is pushing hard to acquire as it adds a gene therapy group to the global mix.

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News­mak­ers at #EHA19: Re­gen­eron, Ar­Qule track progress on re­sponse rates

Re­gen­eron’s close­ly-watched bis­pe­cif­ic con­tin­ues to ring up high re­sponse rates

Re­gen­eron’s high-pro­file bis­pe­cif­ic REGN1979 is back in the spot­light at the Eu­ro­pean Hema­tol­ogy As­so­ci­a­tion sci­en­tif­ic con­fab. And while the stel­lar num­bers we saw at ASH have erod­ed some­what as more blood can­cer pa­tients are eval­u­at­ed, the re­sponse rates for this CD3/CD20 drug re­main high.

A to­tal of 13 out of 14 fol­lic­u­lar lym­phomas re­spond­ed to the drug, a 93% ORR, down from 100% at the last read­out. In 10 out of 14, there was a com­plete re­sponse. In dif­fuse large B-cell lym­phoma the re­sponse rate was 57% among pa­tients treat­ed at the 80 mg to 160 mg dose range. They were all com­plete re­spons­es. And 2 of these Cars were for pa­tients who had failed CAR-T ther­a­py.

Search­ing for the next block­buster to fol­low Darza­lex, J&J finds a $150M an­ti-CD38 drug from part­ner Gen­mab

Now that J&J and Genmab have thrust Darzalex onto the regulatory orbit for first-line use in multiple myeloma, the partners are lining up a deal for a next-gen follow-on to the leading CD38 drug.

Janssen — J&J’s biotech unit — has its eyes on HexaBody-CD38, a preclinical compound generated on Genmab’s tech platform designed to make drugs more potent via hexamerization.

Genmab is footing the bill on studies in multiple myeloma and diffuse large B-cell lymphoma; once it completes clinical proof of concept, Janssen has the option to license the drug for a $150 million exercise fee. There’s also $125 million worth of milestones in play.

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J&J gains an en­thu­si­as­tic en­dorse­ment from Pres­i­dent Don­ald Trump for their big new drug Spra­va­to

Pres­i­dent Don­ald Trump has lit­tle love for Big Phar­ma, but there’s at least one new drug that just hit the mar­ket which he is en­am­ored with.

Trump, ev­i­dent­ly, has been read­ing up on J&J’s new an­ti-de­pres­sion drug, Spra­va­to. And the pres­i­dent — who of­ten likes to break out in­to a full-throat­ed at­tack on greedy drug­mak­ers — ap­par­ent­ly en­thused about the ther­a­py in a meet­ing with of­fi­cials of Vet­er­ans Af­fairs, which has long grap­pled with de­pres­sion among vet­er­ans.

Savara shares are crushed as PhI­II tri­al flunks pri­ma­ry, key sec­on­daries — but they can’t stop be­liev­ing

In­vestors are in no mood to hear biotechs tout the suc­cess of a “key” sec­ondary end­point when the piv­otal Phase III flunks the pri­ma­ry goal. Just ask Savara. 

The Texas biotech $SVRA went look­ing for a sil­ver lin­ing as com­pa­ny ex­ecs blunt­ly con­ced­ed that Mol­gradex, an in­haled for­mu­la­tion of re­com­bi­nant hu­man gran­u­lo­cyte-macrophage colony-stim­u­lat­ing fac­tor (GM-CSF), failed to spur sig­nif­i­cant­ly im­proved treat­ment out­comes for pa­tients with a rare res­pi­ra­to­ry dis­ease called au­toim­mune pul­monary alve­o­lar pro­teinosis, or aPAP.

As an­oth­er an­tibi­otics biotech sinks in­to a cri­sis, warn­ings of a sec­tor ‘col­lapse’

Another antibiotics company is scrambling to survive today, forcing the company’s founding CEO to exit in a reorganization that eliminates its research capabilities as the survivors look to improve on minuscule sales of their newly approved treatment. And the news — on top of an alarming series of failures — spurred at least one figure in the field to warn of a looming collapse of the antimicrobial resistance research field.

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In a boost to Rit­ux­an fran­chise, Roche nabs quick ap­proval for po­latuzum­ab ve­dotin

Roche’s lat­est an­ti­body-drug con­ju­gate has crossed the FDA fin­ish line, gain­ing an ac­cel­er­at­ed ap­proval a full two months ahead of sched­ule.

Po­livy, or po­latuzum­ab ve­dotin, is a first-in-class drug tar­get­ing CD79b — a pro­tein promi­nent in B-cell non-Hodgkin lym­phoma. It will now be mar­ket­ed for dif­fuse large B-cell lym­phoma as part of a reg­i­men that al­so in­cludes the chemother­a­py ben­damus­tine and a ver­sion of rit­ux­imab (Rit­ux­an).