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.”

A new era of treat­ment: How bio­mark­ers are chang­ing the way we think about can­cer

AJ Patel was recovering from a complicated brain surgery when his oncologist burst into the hospital room yelling, “I’ve got some really great news for you!”

For two years, Patel had been going from doctor to doctor trying to diagnose his wheezing, only to be dealt the devastating news that he had stage IV lung cancer and only six months to live. And then they found the brain tumors.

“What are you talking about?” Patel asked. He had never seen an oncologist so happy.

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Michael Corbo, Pfizer CDO of inflammation & immunology

UP­DAT­ED: Plan­ning ahead for crowd­ed ul­cer­a­tive col­i­tis mar­ket, Pfiz­er spells out PhI­II da­ta on $6.7B Are­na drug

Pfizer has laid out the detailed results behind its boast that etrasimod — the S1P receptor modulator at the center of its $6.7 billion buyout of Arena Pharma — is the winner of the class, potentially leapfrogging an earlier entrant from Bristol Myers Squibb.

Pivotal data from the ELEVATE program in ulcerative colitis — which consists of two Phase III trials, one lasting 52 weeks and the other just 12 weeks — illustrate an “encouraging balance of efficacy and safety,” according to Michael Corbo, chief development officer of inflammation & immunology at Pfizer. The company is presenting the results as a late breaker at Digestive Disease Week.

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An NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

'Xeno­trans­plan­ta­tion is com­ing': New NE­JM pa­per gives de­tailed look in­to 2 pig-to-hu­man kid­ney trans­plant cas­es

The thymokidney is a curious organ, if you could call it that. It’s a sort of Frankensteinian creation — a system of pig thymus embedded underneath the outer layer of a pig’s kidney, made for human transplantation.

In the first case of pig-to-human xenotransplantation of a kidney into a brain-dead patient, the thymokidney quietly featured front and center.

In that experiment, which took place in September of last year, NYU researchers led by Robert Montgomery sutured a pig thymokidney onto the leg of a brain-dead 66-year-old woman. That case was widely reported on by a horde of major media outlets, including the New York Times, the BBC, and an in-depth feature by USA Today.

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Vlad Coric, Biohaven CEO

UP­DAT­ED: Fresh off $11.6B sale to Pfiz­er, New Bio­haven hits Phase III set­back just weeks af­ter Vlad Coric chalked up promise

When Pfizer bought up Biohaven’s migraine portfolio in the largest M&A deal of the year earlier this month, Biohaven CEO Vlad Coric promised the rest of the pipeline, which will live on under the umbrella of New Biohaven, still has a lot to offer. But that vision took a dent Monday as the drugmaker revealed it’s once again flopped on troriluzole.

The glutamate regulator failed to meet the primary endpoint on a Phase III study in patients with spinocerebellar ataxia, an inherited disorder that impairs a person’s ability to walk, speak and swallow. SCA can also lead to premature death.

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Mihael Polymeropoulos, Vanda Pharmaceuticals CEO

Phar­ma com­pa­ny con­tin­ues its FDA law­suit spree, this time af­ter agency de­nies fast-track des­ig­na­tion

Vanda Pharmaceuticals is making a name for itself, at least in terms of suing the FDA.

The DC-headquartered firm on Monday filed its latest suit against the agency, with the company raising concerns over the FDA’s failure to grant a fast track designation for Vanda’s potential chronic digestive disorder drug tradipitant, which is a neurokinin 1 receptor antagonist.

Specifically, Vanda said FDA’s “essential point” in its one-page denial letter on the designation pointed to “the lack of necessary safety data,” which was “inconsistent with the criteria for … Fast Track designation.”

Mod­er­na seeks to dis­miss Al­ny­lam suit over Covid-19 vac­cine com­po­nent, claim­ing wrong venue

RNAi therapeutics juggernaut Alnylam Pharmaceuticals made a splash in March when it sued and sought money from both Pfizer and Moderna regarding their use of Alnylam’s biodegradable lipids, which Alnylam claims have been integral to the way both companies’ mRNA-based Covid-19 vaccines work.

But now, Moderna lawyers are firing back, telling the same Delaware district court that Alnylam’s claims can only proceed against the US government in the Court of Federal Claims because of the way the company’s contract is set up with the US government. The US has spent almost $10 billion on Moderna’s Covid-19 vaccine so far.

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(Credit: Shutterstock)

Cracks in the fa­cade: Is phar­ma's pan­dem­ic ‘feel good fac­tor’ wan­ing?

The discordant effects of the Covid-19 pandemic on pharma reputation continues. While the overall industry still retains a respectable halo from its Covid-19 quick response and leadership, a new patient group study reveals a different story emerging in the details.

On one hand, US patient advocacy groups rated the industry higher-than-ever overall. More than two-thirds (67%) of groups gave the industry a thumbs up for 2021, a whopping 10 percentage point increase over the year before, according to the PatientView annual study, now in its 9th year.

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Saqib Islam, SpringWorks CEO

Pfiz­er spin­out Spring­Works will ship its first drug to the FDA be­fore year’s end with PhI­II win

SpringWorks Therapeutics thinks it has cemented the backbone for its first “pipeline-in-a-product” oncology treatment and will send it to the FDA before the clock strikes 2023 with a Phase III win on Tuesday.

The oral gamma secretase inhibitor, dubbed nirogacestat, beat placebo on the primary goal of progression-free survival in adults with progressing desmoid tumors.

The soft-tissue tumors can lead to long-lasting pain, disfigurement and amputation, and there are currently no approved meds for the rare oncology indication. The tumors typically impact patients aged 20 to 44 years old and disproportionately affect women at rates 2 to 3 times higher, with up to a total of 1,650 new cases diagnosed in the US annually, according to SpringWorks.

Robert Califf (Michael Brochstein/Sipa USA via AP Images)

House Re­pub­li­cans at­tack Chi­na-on­ly da­ta in FDA sub­mis­sions, seek new in­ves­ti­ga­tion in­to re­search in­spec­tions

Three Republican representatives are calling on the FDA to take a closer look at the applications including only clinical data from China.

The letter to FDA commissioner Rob Califf late last week comes as the agency recently rejected Eli Lilly’s anti-PD-1 antibody, which attempted to bring China-only data but ran into a bruising adcomm that may crush the hopes of any other companies looking to bring cheaper follow-ons based only on Chinese data.

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