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.

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

Re­gen­eron's Evkeeza shows promise in curb­ing high triglyc­erides, but will ge­net­ic dis­par­i­ties lim­it use?

When Regeneron scored an early approval for lipid lowering antibody Evkeeza back in February, the drugmaker cracked open a new pathway to lower abnormally high cholesterol levels. Now, Regeneron is chasing high triglycerides as well with some promising mid-stage data — but will genetic restrictions limit the drug’s use?

Regeneron’s Evkeeza (evinacumab) cut median triglyceride levels by more than 800 mg/dL (57%) in patients with a rare disorder causing abnormally high triglyceride levels compared with an overall increase of 50 mg/dL (1.8%) in participants on placebo, according to Phase II data presented Sunday at the virtual American College of Cardiology meeting.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; and more

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I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

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As­traZeneca's Farx­i­ga missed big on Covid-19 study, but it's tak­ing SGLT2 safe­ty da­ta as a sil­ver lin­ing

AstraZeneca hasn’t seen many setbacks in recent months for SGLT2 inhibitor Farxiga, which broke ground in heart failure and kidney disease regardless of diabetes diagnosis. But the British drugmaker had to admit defeat in taking Farxiga into Covid-19, but follow-up results add a bit of a silver lining to that trial’s safety data.

Of hospitalized Covid-19 patients dosed with AstraZeneca’s Farxiga, 11.2% experienced an organ failure or died after 30 days of therapy compared with 13.8% of those given placebo, according to follow-up data from the DARE-19 study revealed Sunday at the virtual American College of Cardiology meeting.

Pfiz­er, Bris­tol My­er­s' Eliquis flops in post-heart surgery pa­tients, spurring an 'un­ex­plained sig­nal' in cer­tain deaths

Pfizer and Bristol Myers Squibb’s non-warfarin blood thinner Eliquis has raced out to become the most prescribed drug of its class on the market — even overtaking warfarin’s long-time lead. But in tricky-to-treat patients after a valve replacement, an investigator-sponsored study couldn’t turn up benefit and raised a troubling safety signal.

Eliquis failed to show benefit over standard of care in preventing serious clinical outcomes after a transaortic valve replacement (TAVR) and was linked to an “unexplained signal” in a subset of populations with a higher rate of non-CV deaths who did not need blood thinners apart from the surgery, according to data presented Saturday at the virtual American College of Cardiology meeting.

Gene ther­a­py from Bio­gen's $800M buy­out flops in mid-stage study, deal­ing blow to new am­bi­tions

The #2 candidate from Biogen’s $800 million ocular gene therapy buyout has failed in a mid-stage trial, dealing an early blow to the big biotech’s plans to revitalize its pipeline with new technologies.

Biogen announced that the candidate, an experimental treatment for a rare and progressive form of blindness called X-linked retinitis pigmentosa (XLRP), failed to sufficiently improve vision in patients’ treated eye — patients only received an injection in one eye — after a year, on a standard scale, compared to their untreated eye. The company said they saw “positive trends” on several secondary endpoints, including visual acuity, but declined to say whether the trial actually hit any of those endpoints.

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Michael Dell (Richard Drew, AP Images)

'Dude, you're get­ting a Del­l' — as a new deep-pock­et biotech in­vestor

What happens when you marry longtime insiders in the global biotech VC game with the family fund of tech billionaire Michael Dell, a synthetic biology legend out of MIT and Harvard and the former director of the NCI?

Today, the answer is a newly financed, $200 million biotech SPAC now cruising the industry for a top player interested in finding a short cut to Nasdaq.

Orion Biotech Opportunities priced their blank check company today, raising $200 million with Dell’s multibillion-dollar MSD group’s commitment on investing another $20 million in a forward-purchase agreement.

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Bris­tol My­ers backs up its case for heart drug mava­camten as FDA weighs app in car­diomy­opa­thy

When Bristol Myers Squibb signed off on its $13 billion acquisition of MyoKardia back in October, it was making a big bet that lead drug mavacamten could prove a game changer in cardiac myopathy. Now, with the drug up for FDA review, Bristol Myers is backing up its case with new quality of life data.

Patients dosed with myosin inhibitor mavacamten posted a clinically significant increase in scores on the Kansas City Cardiomyopathy Questionnaire, a catch-all summary of symptoms and quality of life markers, over placebo at 30 weeks, according to data from the Phase III EXPLORER-HCM study presented Saturday at the virtual American College of Cardiology meeting.

Vas Narasimhan (Photographer: Simon Dawson/Bloomberg via Getty Images)

No­var­tis whiffs on En­tresto study af­ter heart at­tacks — but that does­n't mean it's go­ing down qui­et­ly

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.