Sci­en­tists toss an­oth­er Alzheimer’s pro­gram in­to the scrap heap as PhII fails

While a le­gion of sci­en­tists have been em­ployed in failed at­tempts to clear away the tox­ic tan­gles of pro­teins of­ten found in the brains of Alzheimer’s pa­tients, an­oth­er set have con­tin­ued to plug away at the var­i­ous chem­i­cals that play a role in or­ches­trat­ing the brain’s com­plex cel­lu­lar com­mu­ni­ca­tions sys­tem.

But that’s proved just as frus­trat­ing.

Jan Poth

To­day, Boehringer In­gel­heim threw in the tow­el on an Alzheimer’s pro­gram for a drug called BI 409306, an­oth­er ef­fort to see if they could do a bet­ter job in mod­u­lat­ing glu­ta­mate, one of those neu­ro­trans­mit­ters that can run amuck in de­men­tia.

The drug works by block­ing a pro­tein called PDE 9A which they be­lieved would en­hance cell sig­nal­ing in the glu­ta­mater­gic com­mand cen­ter in the brain. Re­searchers re­cruit­ed 457 pa­tients for two stud­ies, but like every­thing else that’s been put to a de­fin­i­tive test in the past 15 years, it failed to beat a place­bo in im­prov­ing cog­ni­tion.

It’s a log­i­cal field to ex­plore. Na­men­da was ap­proved by the FDA 15 years ago af­ter it was brought in from Eu­rope, where it had been used for years. That’s a glu­ta­mater­gic drug, fo­cus­ing on the NM­DA re­cep­tor — a big play­er in de­pres­sion. The drug tem­porar­i­ly mod­u­lates cog­ni­tive symp­toms of a dis­ease that grad­u­al­ly wipes out mem­o­ries.

Boehringer hasn’t giv­en up on the drug. It has plans to test it in schiz­o­phre­nia. And there’s a GlyT1 in­hibitor — an­oth­er glu­ta­mate drug called BI 425809 — which is be­ing test­ed in Alzheimer’s and oth­er CNS dis­eases.

The fail­ure rate for Alzheimer’s drug has been run­ning par­tic­u­lar­ly hot of late. We re­cent­ly got a close look at just how bad­ly Eli Lil­ly’s solanezum­ab failed to al­ter the course of the dis­ease by fo­cus­ing on amy­loid be­ta. Ax­o­vant cratered af­ter back-to-back fail­ures on a 5HT6 drug, an­oth­er symp­to­matic ef­fort fo­cused on a key neu­ro­trans­mit­ter. And Pfiz­er capped off the string of set­backs by call­ing it quits in the field, wip­ing out a pipeline of drugs and lay­ing off 300 peo­ple work­ing in the area.

Big play­ers like Bio­gen, though, con­tin­ue to in­vest heav­i­ly, con­vinced that they can suc­ceed where all oth­ers failed. And an up­start like De­nali can pull off a record-set­ting IPO by promis­ing to pur­sue new strate­gies.

But the odds in this field are par­tic­u­lar­ly tough, in an in­dus­try where fail­ure is a dai­ly re­al­i­ty.

“We recog­nise the im­mense an­tic­i­pa­tion around any progress in brain re­search that brings us clos­er to find­ing so­lu­tions for the many mil­lions of peo­ple liv­ing with de­men­tia. How­ev­er, this is what re­search is about: dis­ap­point­ments are a dai­ly ex­pe­ri­ence in sci­ence, but even these clin­i­cal tri­al re­sults will add to the un­der­stand­ing of brain func­tion and con­tribute to fu­ture progress in this area.” said Jan Poth, ther­a­peu­tic area head of CNS and im­munol­o­gy at Boehringer In­gel­heim.

Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology
ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development
CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at with any issues.

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Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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Why would Am­gen want to buy Alex­ion? An­a­lysts call hot­ly ru­mored takeover un­like­ly, but seize the mo­ment

A rumor that Amgen is closing in on buyout deal for Alexion has sparked a guessing game on just what kind of M&A strategy Amgen is pursuing and how much Alexion is worth.

Mizuho analyst Salim Syed first lent credence to the report out of the Spanish news outlet Intereconomía, which said Amgen is bidding as much as $200 per share. While the source may be questionable, “the concept of this happening doesn’t sound too crazy to me,” he wrote.

FDA asks why No­var­tis took two months to launch for­mal in­ter­nal probe, af­ter AveX­is flagged da­ta ma­nip­u­la­tion

And the plot thickens. Novartis $NVS officials are reportedly now scrambling to explain to the FDA why it took them two months to open an internal investigation into data discrepancies for their $2.1 million gene-therapy for spinal muscular dystrophy — the world’s most expensive drug.

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Hal Barron. GSK

GSK's Hal Bar­ron her­alds their sec­ond pos­i­tive piv­otal for cru­cial an­ti-BC­MA ther­a­py, point­ing to a push for quick OKs in a crowd­ed field

Hal Barron has his second positive round of Phase III data in hand for his anti-BCMA antibody drug conjugate belantamab mafodotin (GSK2857916). And GSK’s research chief says the data paves the way for their drive in search of an FDA approval for treating multiple myeloma.

It’s hard to overestimate the importance of this drug for GSK, a cornerstone of Barron’s campaign to make a dramatic impact on the oncology market and provide some long-lost excitement for the pharma giant’s pipeline. They’re putting this BCMA program at the front of that charge — looking to lead a host of rivals all aimed at the same target.

We don’t know what the data are yet, but DREAMM-2 falls on the heels of a promising set of data delivered 5 months ago for DREAMM-1. There investigators noted that complete responses among treatment-resistant patients rose to 15% in the extra year’s worth of data to look over, with a median progression-free survival rate of 12 months, up from 7.9 months reported earlier. The median duration of response was 14.3 months.

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UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

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Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll