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.”

Mer­ck is tak­ing the ax to its US op­er­a­tions, cut­ting 500 jobs in its lat­est re­or­ga­ni­za­tion

Merck is cutting 500 jobs in its US sales and headquarters commercial teams in its latest effort to find new ways to streamline the operation.

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Top ALK ex­pert and can­cer drug re­searcher Al­ice Shaw bids adieu to acad­e­mia, hel­lo to No­var­tis

Jay Bradner has recruited a marquee oncology drug researcher into the ranks of the Novartis Institutes for BioMedical Research. Alice Shaw is jumping from prestigious posts intertwined through Mass General, Harvard and Dana-Farber to take the lead of NIBR’s translational clinical oncology group.

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Hal Barron, GSK's president of R&D and CSO, speaks to Endpoints News founder and editor John Carroll in London at Endpoints' #UKBIO19 summit on October 8, 2019

[Video] Cel­e­brat­ing tri­al fail­ures, chang­ing the cul­ture and al­ly­ing with Cal­i­for­nia dream­ers: R&D chief Hal Bar­ron talks about a new era at GSK

Last week I had a chance to sit down with Hal Barron at Endpoints’ #UKBIO19 summit to discuss his views on R&D at GSK, a topic that has been central to his life since he took the top research post close to 2 years ago. During the conversation, Barron talked about changing the culture at GSK, a move that involves several new approaches — one of which involves celebrating their setbacks as they shift resources to the most promising programs in the pipeline. Barron also discussed his new alliances in the Bay Area — including his collaboration pact with Lyell, which we covered here — frankly assesses the pluses and minuses of the UK drug development scene, and talks about his plans for making GSK a much more effective drug developer.

This is one discussion you won’t want to miss. Insider and Enterprise subscribers can log-in to watch the video.

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Med­ical an­i­ma­tion: Mak­ing it eas­i­er for the site and the pa­tient to un­der­stand

Medical animation has in recent years become an increasingly important tool for conveying niche information to a varied audience, particularly to those audiences without expertise in the specialist area. Science programmes today, for example, have moved from the piece-to-camera of the university professor explaining how a complex disease mechanism works, to actually showing the viewer first-hand what it might look like to shrink ourselves down to the size of an ant’s foot, and travel inside the human body to witness these processes in action. Effectively communicating a complex disease pathophysiology, or the novel mechanism of action of a new drug, can be complex. This is especially difficult when the audience domain knowledge is limited or non-existent. Medical animation can help with this communication challenge in several ways.
Improved accessibility to visualisation
Visualisation is a core component of our ability to understand a concept. Ask 10 people to visualise an apple, and each will come up with a slightly different image, some apples smaller than others, some more round, some with bites taken. Acceptable, you say, we can move on to the next part of the story. Now ask 10 people to visualise how HIV’s capsid protein gets arranged into the hexamers and pentamers that form the viral capsid that holds HIV’s genetic material. This request may pose a challenge even to someone with some virology knowledge, and it is that inability to effectively visualise what is going on that holds us back from fully understanding the rest of the story. So how does medical animation help us to overcome this visualisation challenge?

Flu Virus (Source: CDC)

FDA ex­pands Xofluza ap­proval as Roche strug­gles to catch loom­ing flu mar­ket

As a potentially powerful flu season looms, so does a big test for Roche and its new flu drug, Xofluza. The Swiss giant just got a small boost in advance of that test as the FDA expanded Xofluza’s indication to include patients at high risk of developing flu-related complications.

Xofluza (baloxavir marboxil) was approved last October in the US, the first landmark flu drug approval in 20 years and a much-needed green light for a company that had watched its leading flu drug Tamiflu get eaten alive by generics. Like its predecessor, the pill offered a reduction in flu symptoms but not a cure.

EMA backs sev­en ther­a­pies, in­clud­ing Mer­ck­'s Ebo­la vac­cine

The first-ever Ebola vaccine is on the precipice of approval after the European Medicine’s Agency (EMA) backed the Merck product in this week’s roster of recommendations.

The drugmaker $MRK began developing the vaccine, christened Ervebo, during the West African outbreak that occurred between 2014 and 2016, killing more than 11,000.

The current outbreak in the Democratic Republic of Congo (DRC) has shown case fatality rates of approximately 67%, the agency estimated. Earlier this year, the WHO declared the outbreak — which so far has infected more than 3,000 people — a public health emergency of international concern.

Ronald Herb­st fol­lows Med­Im­mune ex­o­dus to Pyx­is CSO post; Jeff God­dard to suc­ceed CEO of AIT Bio­science

→ The outflow of top execs from MedImmune continues to fill the leadership ranks of smaller biotechs. The latest to take off is Ronald Herbst, the head of oncology research, who’s assuming the CSO post at Pyxis Oncology.  

Herbst was part of the old MedImmune organization AstraZeneca CEO Pascal Soriot restructured earlier this year, reorganizing the company and eliminating the storied subsidiary as a separate organization.

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UP­DAT­ED: J&J's Xarel­to, Amar­in's Vas­cepa are cost-ef­fec­tive, not bud­get friend­ly — ICER

ICER, an increasingly influential cost-effectiveness watchdog in the United States, has concluded in its review of treatments for cardiovascular disease that while the cost of J&J’s Xarelto and Amarin’s Vascepa meet its benchmark for value pricing — the two treatments will not likely treat as many patients as hoped without surpassing the annual budget threshold calculated by ICER for each therapy.

Mi­rati preps its first look at their KRAS G12C con­tender, and they have to clear a high bar for suc­cess

If you’re a big KRAS G12C fan, mark your calendars for October 28 at 4:20 pm EDT.

That’s when Mirati $MRTX will unveil its first peek at the early clinical data available on MRTX849 in presentations at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.

Mirati has been experiencing the full effect of a rival’s initial success at targeting the G12C pocket found on KRAS, offering the biotech some support on the concept they’re after — and biotech fans a race to the top. Amgen made a big splash with its first positive snapshot on lung cancer, but deflated sky-high expectations as it proved harder to find similar benefits in other types of cancers.

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