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.”

UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

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This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

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For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
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What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

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The FDA has de­val­ued the gold stan­dard on R&D. And that threat­ens every­one in drug de­vel­op­ment

Bioregnum Opinion Column by John Carroll

A few weeks ago, when Stephen Hahn was being lightly queried by Senators in his confirmation hearing as the new commissioner of the FDA, he made the usual vow to maintain the gold standard in drug development.

Neatly summarized, that standard requires the agency to sign off on clinical data — usually from two, well-controlled human studies — that prove a drug’s benefit outweighs any risks.

Over the last few years, biopharma has enjoyed an unprecedented loosening over just what it takes to clear that bar. Regulators are more willing to drop the second trial requirement ahead of an accelerated approval — particularly if they have an unmet medical need where patients are clamoring for a therapy.

That confirmatory trial the FDA demands can wait a few years. And most everyone in biopharma would tell you that’s the right thing for patients. They know its a tonic for everyone in the industry faced with pushing a drug through clinical development. And it’s helped inspire a global biotech boom.

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UP­DAT­ED: New play­ers are jump­ing in­to the scram­ble to de­vel­op a vac­cine as pan­dem­ic pan­ic spreads fast

When the CNN news crew in Wuhan caught wind of the Chinese government’s plan to quarantine the city of 11 million people, they made a run for one of the last trains out — their Atlanta colleagues urging them on. On the way to the train station, they were forced to skirt the local seafood market, where the coronavirus at the heart of a brewing outbreak may have taken root.

And they breathlessly reported every moment of the early morning dash.

In shuttering the city, triggering an exodus of masked residents who caught wind of the quarantine ahead of time, China signaled that they were prepared to take extreme actions to stop the spread of a virus that has claimed 17 lives, sickened many more and panicked people around the globe.

CNN helped illustrate how hard all that can be.

The early reaction in the biotech industry has been classic, with small-cap companies scrambling to headline efforts to step in fast. But there are also new players in the field with new tech that has been introduced since the last of a series of pandemic panics that could change the usual storylines. And they’re volunteering for a crash course in speeding up vaccine development — a field where overnight solutions have been impossible to prove.

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Mer­ck KGaA spin­out gets first fund­ing to bring dual-act­ing can­cer mol­e­cules in­to the clin­ic

Two and a half years after launch, Merck KGaA spinout iOnctura is getting its first major round of funding.

The oncology startup raised €15 million ($16.6 million) to put its lead drug into the clinic and get its second drug past IND-enabling tests. INKEF Capital and VI Partners co-led the round and were joined by the biotech’s longtime backer M Ventures, an arm of Merck KGaA, and Schroder Adveq.

UP­DAT­ED: Eli Lil­ly’s $1.6B can­cer drug failed to spark even the slight­est pos­i­tive gain for pa­tients in its 1st PhI­II

Eli Lilly had high hopes for its pegylated IL-10 drug pegilodecakin when it bought Armo last year for $1.6 billion in cash. But after reporting a few months ago that it had failed a Phase III in pancreatic cancer, without the data, its likely value has plunged. And now we’re getting some exact data that underscore just how little positive effect it had.

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Am­gen aug­ments Asia foothold by tak­ing over Astel­las joint ven­ture in Japan

California-based Amgen, which does the bulk of its business in the United States, made its ambition to reinvigorate its growth prospects by expanding its presence in Asia clear at the sidelines of the JP Morgan healthcare conference in San Francisco earlier this month.

The Thousand Oaks-based company on Thursday executed its plan to dissolve the joint venture with Astellas — created in 2013 — to operate the unit independently in Japan. With its rapidly aging population, the region represents an appealing market for Amgen’s osteoporosis treatments Prolia and Evenity as well as a cholesterol-lowering injection Repatha.

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PureTech bags $200M from sale of Karuna shares — still siz­zling from promis­ing schiz­o­phre­nia da­ta

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