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.”

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data is messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data is exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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David Lockhart, ReCode Therapeutics CEO

Pfiz­er throws its weight be­hind LNP play­er eye­ing mR­NA treat­ments for CF, PCD

David Lockhart did not see the meteoric rise of messenger RNA and lipid nanoparticles coming.

Thanks to the worldwide fight against Covid-19, mRNA — the genetic code that can be engineered to turn the body into a mini protein factory — and LNPs, those tiny bubbles of fat carrying those instructions, have found their way into hundreds of millions of people. Within the biotech world, pioneers like Alnylam and Intellia have demonstrated just how versatile LNPs can be as a delivery vehicle for anything from siRNA to CRISPR/Cas9.

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No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty

 

I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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Pascal Soriot, AstraZeneca CEO (via Getty images)

UP­DAT­ED: FDA slaps As­traZeneca's MCL-1 can­cer drug with a hold af­ter safe­ty is­sue — 2 years af­ter Am­gen axed a trou­bled ri­val

There are new questions being posed about a class of cancer drugs in the wake of the second FDA-enforced clinical hold in the field.

Two years after the FDA hit Amgen with a clinical hold on its MCL-1 inhibitor AMG 397 following signs of cardiac toxicity, AstraZeneca says that regulators hit them with a hold on their rival therapy of the same class.

The pharma giant noted on clinicaltrials.gov that its Phase I/II study for the MCL-1 drug AZD5991 “has been put on hold to allow further evaluation of safety related information.”

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Sur­geons suc­cess­ful­ly at­tach pig kid­ney to a hu­man for the first time, us­ing tech from Unit­ed's Re­vivi­cor

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Surgeons spent three days attaching the kidney to the patient’s blood vessels, but when all was said and done, the kidney appeared to be functioning normally in early testing, Reuters and the New York Times were among those to report. The kidney came from a genetically altered pig developed through United’s Revivicor unit.

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Leen Kawas (L) has resigned as CEO of Athira and will be replaced by COO Mark Litton

Ex­clu­sive: Athi­ra CEO Leen Kawas re­signs af­ter in­ves­ti­ga­tion finds she ma­nip­u­lat­ed da­ta

Leen Kawas, CEO and founder of the Alzheimer’s upstart Athira Pharma, has resigned after an internal investigation found she altered images in her doctoral thesis and four other papers that were foundational to establishing the company.

Mark Litton, the company’s COO since June 2019 and a longtime biotech executive, has been named full-time CEO. Kawas, meanwhile, will no longer have ties to the company except for owning a few hundred thousand shares.

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Sen. Richard Durbin (D-IL, foreground) and Sen. Richard Blumenthal (D-CT) (Patrick Semansky/AP Images)

Sen­a­tors back FDA's plan to re­quire manda­to­ry pre­scriber ed­u­ca­tion for opi­oids

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Bris­tol My­ers pledges to sell its Ac­celeron shares as ac­tivist in­vestors cir­cle Mer­ck­'s $11.5B buy­out — re­port

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The pharma giant is planning to tender its Acceleron shares, Bloomberg reported, which add up to a sizable 11.5% stake. Based on the offer price, the sale would net Bristol Myers around $1.3 billion.

To complete its deal, Merck needs a majority of shareholders to agree to sell their shares.