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.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

The End­points 11: They've got mad mon­ey and huge am­bi­tions. It's time to go big or go home

These days, selecting a group of private biotechs for the Endpoints 11 spotlight begins with a sprint to get ahead of IPOs and the M&A teams at Big Pharma. I’ve had a couple of faceplants earlier this year, watching some of the biotechs on my short list choose a quick leap onto Nasdaq or into the arms of a buyer.

Vividion, you would have been a great pick for the Endpoints 11. I’m sorry I missed you.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Dave Lennon, former president of Novartis Gene Therapies

So what hap­pened with No­var­tis Gene Ther­a­pies? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

FDA au­tho­rizes Pfiz­er's vac­cine boost­er for se­niors, those at high risk for se­vere Covid-19

The Biden administration’s goal of kicking off its booster shot drive for the entire US population this week is not quite going as planned.

First, Pfizer applied for approval of a supplemental application for the booster shots, but since last Friday’s adcomm reviewing them, the plan has devolved into an EUA, which the FDA issued late Thursday evening.

The population that is now eligible for the booster, six months after receiving the first pair of Pfizer-BioNTech vaccines, also narrowed from what Pfizer applied for (everyone who’s eligible for the initial Pfizer shots) to just those who are 65 or older, or at high-risk of a Covid infection, including health care workers and others with occupational hazards.

Stéphane Bancel, AP Images

Fi­nal analy­sis of US-fund­ed Mod­er­na Covid vac­cine tri­al shows 98% ef­fi­ca­cy against se­vere dis­ease

A final look at the results of the placebo-controlled Moderna trial in the New England Journal of Medicine, published Thursday afternoon, shows how the vaccine continues to prevent Covid-19 and severe cases after more than five months following the second shot.

Of the more than 30,000 enrolled in the trial that ultimately led to the vaccine’s EUA, only two people in the vaccine group got a severe form of the disease, compared to 106 in the placebo group — leading to an efficacy of 98%.

Emma Walmsley, GlaxoSmithKline CEO (Credit: Fang Zhe/Xinhua/Alamy Live News)

The fire un­der Glax­o­SmithK­line's Em­ma Walm­s­ley grows as an­oth­er well-known ac­tivist in­vestor grabs its pitch­fork — re­port

Bluebell Capital Partners, a proxy brawler fresh off a campaign to oust global food giant Danone’s CEO and most of its board of directors, has bought a stake in UK drugmaker GlaxoSmithKline with its eyes trained directly on Emma Walmsley, the Financial Times reported Wednesday.

The London-based hedge fund joins another notorious activist firm in Paul Singer’s Elliott Management, which earlier this year called for a shakeup in leadership at GSK to handle what the company described as a wealth of riches across the drug giant’s portfolio hindered by limited vision from top staff.

FDA+ roundup: Bs­U­FA III ready for show­time, court tells FDA to re-work com­pound­ing plan, new guid­ance up­dates and more

The FDA has now spelled out what exactly will be included in the third iteration of Biosimilar User Fee Act (BsUFA) from 2023 through 2027, which similarly to the prescription drug deal, sets fees that industry has to pay for submitting applications, in exchange for firm timelines that the agency must meet.

This latest deal includes several sweeteners for the biosimilar industry, which has yet to make great strides in the US market, with shorter review timelines for safety labeling updates and updates to add or remove an indication that does not contain efficacy data.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Joshua Liang, Clover Biopharmaceuticals CEO

With world still in sore need of dos­es, Clover says its Covid-19 vac­cine is 67% ef­fec­tive in Phase III

With concerns about the Delta variant rising and much of the world still in desperate need of vaccine doses, a Chinese biotech announced Wednesday that a new shot has shown positive results in a large trial against Covid-19, including new variants.

Clover Biopharmaceuticals announced Wednesday that its vaccine candidate showed 79% efficacy against the Delta variant in a Phase II/III trial dubbed Spectra, and 67% effective against Covid-19 overall.