Aca­dia shares skid as Nu­plazid clears mid-stage hur­dle for Alzheimer’s psy­chosis, but skep­tics pounce

Steve Davis, Aca­dia

Shares of San Diego-based Aca­dia Phar­ma­ceu­ti­cals $ACAD shot up this morn­ing af­ter the com­pa­ny scored a suc­cess in a mid-stage study of its 5-HT2A -tar­get­ing drug Nu­plazid (pi­ma­vanserin) in Alzheimer’s dis­ease psy­chosis. But the biotech al­so had to face off against some ex­pert opin­ion that was not in the least bit im­pressed by the re­sults, es­pe­cial­ly fac­tor­ing in a failed sec­ondary end­point that forced shares to slide back in the back­lash.

Aca­dia’s drug — al­ready ap­proved for Parkin­son’s dis­ease psy­chosis — hit the pri­ma­ry end­point in the mid-stage test. Us­ing the NPI-NH Psy­chosis score, in­ves­ti­ga­tors tracked a 3.76 point im­prove­ment in psy­chosis at week 6 com­pared to a 1.93 point im­prove­ment for place­bo, a sta­tis­ti­cal­ly sig­nif­i­cant re­sponse. There were 181 pa­tients en­rolled in the study.

While much of the field is fo­cused on ei­ther amy­loid be­ta or tau, two tox­ic pro­teins that may trig­ger the Alzheimer’s, Aca­dia is fo­cused on treat­ing symp­toms of the dis­ease. Al­ready pegged as a like­ly block­buster, a new ap­proval for Alzheimer’s could sig­nif­i­cant­ly ex­pand this drug’s mar­ket reach, though the biotech has some ways to go be­fore it can make a start.

One big prob­lem for Aca­dia: Their drug failed to hit an im­por­tant mile­stone on the psy­chosis score at week 12. In their 8-K, filed to­day, the com­pa­ny con­cedes the fail­ure, not­ing: “On the sec­ondary end­point of mean change in NPI-NH Psy­chosis score at week 12, pi­ma­vanserin main­tained the im­prove­ment on psy­chosis ob­served at the week six pri­ma­ry end­point, but did not sta­tis­ti­cal­ly sep­a­rate from place­bo.”

Al­fre­do Fontani­ni, an as­so­ciate pro­fes­sor of neu­ro­bi­ol­o­gy at Stony Brook Uni­ver­si­ty School of Med­i­cine, was not im­pressed, tweet­ing that “this is not a sig­nal find­ing tri­al, we know Pi­ma af­fects hal­lu­ci­na­tions, point is can it sus­tain it at 12 weeks in ADP? No, er­go fail.”

Paul Mat­teis at Leerink al­so raised some thorny ques­tions about the drug’s fu­ture. He wrote:

(T)his wasn’t a free call op­tion in our view, but in any case we ex­pect the shares to trade mean­ing­ful­ly high­er to­day on the news as the ADP mar­ket and the AD ag­i­ta­tion mar­kets are very large. Nonethe­less, look­ing ahead, we note that the ben­e­fit in this study is small­er than that seen in PDP, and it is un­clear (1) whether or not ACAD can use the NPI psy­chosis score as a Ph 3 end­point (should it de­cide to ad­vance the pro­gram), (2) whether this re­sult, which was gen­er­at­ed at a set of nurs­ing homes af­fil­i­at­ed with the King’s Col­lege of Lon­don, is replic­a­ble across a larg­er num­ber of clin­i­cal cen­ters, and (3) what kind of safe­ty data­base the FDA will re­quire (we’d ex­pect it to be large, giv­en the agency’s cur­rent ap­proach to la­bel­ing risks) to ap­prove an an­ti-psy­chot­ic in Alzheimer’s.

Those ques­tions be­gan to in­flu­ence in­vestors’ at­ti­tudes ear­ly to­day. Aca­dia’s stock, which ini­tial­ly spiked 50%, was up on­ly 13% af­ter the mar­ket opened.

Nu­plazid won FDA ap­proval last spring, but on­ly af­ter reg­u­la­tors ex­pressed their safe­ty con­cerns, not­ing a dis­tinct in­crease in the num­ber of deaths as well as the rate of ad­verse events among the pa­tients tak­ing the drug com­pared to the con­trol arm of the study — even if there was no ob­vi­ous clue what was trig­ger­ing those events.

“Alzheimer’s dis­ease pa­tients suf­fer from a num­ber of de­bil­i­tat­ing symp­toms, of which psy­chosis car­ries a poor prog­no­sis and is as­so­ci­at­ed with ear­li­er place­ment in­to nurs­ing homes,” said Steve Davis, Aca­dia’s Pres­i­dent and Chief Ex­ec­u­tive Of­fi­cer. “Da­ta from the -019 Study pro­vide sol­id ev­i­dence that pi­ma­vanserin can im­prove psy­chosis in an­oth­er ma­jor neu­ro­log­i­cal dis­or­der and pro­vide strate­gic mo­men­tum for the fur­ther de­vel­op­ment of pi­ma­vanserin to ad­dress the needs of AD Psy­chosis pa­tients.”

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 help@endpointsnews.com 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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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

As­traZeneca’s Imfinzi/treme com­bo strikes out — again — in lung can­cer. Is it time for last rites?

AstraZeneca bet big on the future of their PD-L1 Imfinzi combined with the experimental CTLA-4 drug tremelimumab. But once again it’s gone down to defeat in a major Phase III study — while adding damage to the theory involving targeting cancer with a high tumor mutational burden.

Early Wednesday the pharma giant announced that their NEPTUNE study had failed, with the combination unable to beat standard chemo at overall survival in high TMB cases of advanced non-small cell lung cancer. We won’t get hard data until later in the year, but the drumbeat of failures will call into question what — if any — future this combination can have left.

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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.