Aca­dia un­veils the pos­i­tive PhI­II it's tak­ing to FDA for ex­pand­ing Nu­plazid's use in psy­chosis

Aca­dia Phar­ma­ceu­ti­cals has bro­ken out the num­bers prop­ping up Nu­plazid’s sur­prise ear­ly win in a Phase III de­men­tia study and, ac­cord­ing to one an­a­lyst, it’s “as good as we could have hoped for.”

The biotech stunned in­vestors three months ago when they an­nounced they’re halt­ing the HAR­MO­NY tri­al, hav­ing ob­tained enough pos­i­tive da­ta at an in­ter­im read­out to make a pitch to the FDA. It came as a sur­prise and stirred up a ral­ly around Aca­dia’s stock $ACAD, which has suf­fered from pre­vi­ous failed at­tempts at ex­pand­ing the con­tro­ver­sial Parkin­son’s dis­ease psy­chosis drug be­yond the ap­proved pa­tient pop­u­la­tion.

Serge Stankovic

Pre­sent­ing at the Clin­i­cal Tri­als on Alzheimer’s Dis­ease meet­ing — al­though they al­so en­rolled pa­tients with oth­er types of de­men­tia — Aca­dia in­ves­ti­ga­tors said Nu­plazid (pi­ma­vanserin) re­duced the risk of pa­tients’ psy­chosis com­ing back by 2.8 fold. The haz­ard ra­tio was 0.353 for the pri­ma­ry end­point, with a one-sided p-val­ue of 0.0023.

“The mag­ni­tude of ef­fect was strong for the HR and p-val­ue, as the pri­ma­ry end­point p-val­ue (p=0.0023) hit well be­low the bar for stop­ping the tri­al ear­ly (p=0.0033),” Marc Good­man of SVB Leerink wrote in a note.

On the sec­ondary end­point, Nu­plazid was found to have re­duced the risk of dis­con­tin­u­a­tion for any rea­son by 2.2 fold (HR=0.452, one-sided p=0.0024).

The re­sults add up to an im­por­tant ad­vance for the 8 mil­lion pa­tients with de­men­tia in the US, up to 30% of whom can de­vel­op psy­chosis, ac­cord­ing to tri­al leader Jef­frey Cum­mings.

“Re­duc­ing the risk of re­lapse of psy­chot­ic symp­toms by this mag­ni­tude is an im­por­tant and mean­ing­ful out­come as these are se­ri­ous events which could lead to poor pa­tient out­comes and a sig­nif­i­cant in­crease in care­giv­er bur­den and dis­tress,” said Cum­mings, who’s al­so the di­rec­tor emer­i­tus of the Cleve­land Clin­ic Lou Ru­vo Cen­ter for Brain Health in Las Ve­gas, in a state­ment.

While the study, which en­rolled 392 pa­tients in to­tal, was not pow­ered to reach con­clu­sions about in­di­vid­ual sub­groups, Good­man saw the da­ta as good enough to cov­er a broad la­bel. No­tably, Aca­dia ex­ecs had orig­i­nal­ly in­tend­ed to fo­cus on Alzheimer’s dis­ease psy­chosis but broad­ened the reach to de­men­tia with Lewy bod­ies, Parkin­son’s dis­ease de­men­tia, vas­cu­lar de­men­tia and fron­totem­po­ral de­men­tia when they fi­nal­ly kicked off the study in 2017. And it’s pay­ing off.

A meet­ing re­gard­ing an sN­DA with FDA reg­u­la­tors — who had grant­ed them break­through ther­a­py des­ig­na­tion for de­men­tia-re­lat­ed psy­chosis — is in the works for the first half of 2020, said Aca­dia pres­i­dent Serge Stankovic.

There are cur­rent­ly no ap­proved treat­ments for de­men­tia-re­lat­ed psy­chosis, Good­man not­ed, and the an­tipsy­chotics typ­i­cal­ly pre­scribed off-la­bel can have poor tol­er­a­bil­i­ty, neg­a­tive­ly im­pact cog­ni­tion, and cause move­ment dis­or­ders.

Ob­ser­va­tions through­out nine months of treat­ment — for pa­tients who were on the drug both dur­ing the ini­tial three-month open-la­bel por­tion and the sub­se­quent dou­ble-blind, place­bo-con­trolled seg­ment — sug­gest­ed that Nu­plazid didn’t have those com­mon side ef­fects.

Aca­dia re­port­ed that 61.8% of the pa­tients who went through open-la­bel treat­ment pre-ran­dom­iza­tion grad­u­at­ed to the sec­ond phase.

From Good­man:

The safe­ty pro­file was in line with the cur­rent Nu­plazid la­bel in PDP, and the Nu­plazid arm was sim­i­lar to the place­bo arm on AEs (41.0% Nu­plazid, 36.6% place­bo) and dis­con­tin­u­a­tions due to AEs (2.9% Nu­plazid, 3.6% place­bo). Man­age­ment high­light­ed that <10% of pa­tients were treat­ed with the low­er 20mg dose, demon­strat­ing a fa­vor­able tol­er­a­bil­i­ty of the 34mg dose.

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The drugmaker formally pleaded guilty to three criminal charges, the AP reported, including getting in the way of the DEA’s efforts to combat the crisis, failing to prevent the painkillers from ending up on the black market and encouraging doctors to write more painkiller prescriptions through two methods: paying them in a speakers program and directing a medical records company to send them certain patient information. Purdue’s plea deal calls for $8.3 billion in criminal fines and penalties, but the company is only liable for a fraction of that total — $225 million.

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The Danish biotech reported Tuesday that it decided to kill their program for enapotamab vedotin after the data gathered from expansion cohorts failed to measure up. According to the company:

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Vas Narasimhan, Novartis CEO (Jason Alden/Bloomberg via Getty Images)

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Bahija Jallal (file photo)

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John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

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