Aca­dia says Nu­plazid cleared main goal in de­pres­sion study, but da­ta ap­pear mixed

In a news-heavy week for de­pres­sion drugs, with of­fer­ings from Alk­er­mes $ALKS and Sage $SAGE un­der FDA scruti­ny, Aca­dia Phar­ma­ceu­ti­cals $ACAD on Wednes­day said “weight­ed av­er­age re­sults” sug­gest pi­ma­vanserin (Nu­plazid) met the main goal in a mid-stage study in­volv­ing pa­tients with ma­jor de­pres­sive dis­or­der (MDD) — but a con­tro­ver­sial two-stage tri­al de­sign in­di­cat­ed the drug failed to im­press in the sec­ond tranche of the tri­al, de­spite the p-val­ue that emerged from the pooled da­ta.

Al­though ini­tial en­thu­si­asm pushed the stock up in pre-mar­ket trad­ing, it was in the red once the mar­ket opened on Wednes­day morn­ing.

Tri­als test­ing drugs for psy­chi­atric dis­or­ders are sus­cep­ti­ble to a large place­bo ef­fect and typ­i­cal­ly fail. In an ef­fort to avoid this, Aca­dia’s CLAR­I­TY tri­al test­ed pi­ma­vanserin us­ing the same se­quen­tial par­al­lel com­par­i­son de­sign (SPCD) as Alk­er­mes’ de­pres­sion drug ALKS 5461, which was al­so the sub­ject of much con­fu­sion in a staff re­view post­ed by the reg­u­la­tor on Tues­day — the de­sign brought up a host of un­re­solved sta­tis­ti­cal ques­tions re­gard­ing the most ap­pro­pri­ate method of analy­sis in SPCD.

The SPCD de­sign in­volves two stages:

  • In the first stage, pa­tients ei­ther get the drug or a place­bo, but more pa­tients are ran­dom­ized to get the place­bo
  • In the sec­ond stage, non-re­spon­ders from the place­bo group are re-ran­dom­ized to get the drug or the place­bo

Re­sults from the two stages are then pooled to pro­vide a sin­gle over­all test of hy­poth­e­sis. The tri­al test­ed pi­ma­vanserin against a place­bo in 207 adult MDD pa­tients who had not ad­e­quate­ly re­spond­ed to ex­ist­ing first-line ther­a­py.

In the first stage, pa­tients on pi­ma­vanserin (n=52) demon­strat­ed a sig­nif­i­cant im­prove­ment in HAMD-17 (p=0.0003) ver­sus place­bo (n=155).

But sig­nif­i­cant­ly, in the sec­ond stage, pa­tients on pi­ma­vanserin (n=29) did not show a sig­nif­i­cant sep­a­ra­tion from place­bo (n=29), prompt­ing crit­ics to sug­gest the tri­al was a fail­ure dressed in sheep’s cloth­ing.

Aca­dia con­clud­ed that in the “weight­ed merged analy­sis” of the two stages, the drug just met the main goal (p=0.039) of in­duc­ing a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion in de­pres­sive symp­toms on the Hamil­ton de­pres­sion rat­ing scale (HAMD-17) com­pared to place­bo. Dis­con­tin­u­a­tions due to ad­verse events were 1.2% for pi­ma­vanserin and 3.2% for place­bo, and one pa­tient in the pi­ma­vanserin group and the place­bo arm re­port­ed se­ri­ous ad­verse events, but these SAEs were deemed not to be re­lat­ed to the drug and both sub­jects com­plet­ed the study, Aca­dia said.

Pi­ma­vanserin be­longs to a class of drugs called se­lec­tive sero­tonin in­verse ag­o­nists (SSIA), which tar­gets the 5-HT2A re­cep­tor that is be­lieved to play a crit­i­cal role in de­pres­sion, psy­chosis, and oth­er neu­ropsy­chi­atric dis­or­ders.

The con­tro­ver­sial drug, which is al­ready sold un­der the brand name Nu­plazid for Parkin­son’s dis­ease psy­chosis, gained no­to­ri­ety af­ter a se­ries of re­ports sug­gest­ed its mak­er had mis­rep­re­sent­ed the dan­gers of us­ing the drug and had em­ployed ques­tion­able tac­tics to mar­ket it, prompt­ing an FDA re­view that lat­er reaf­firmed the drug’s safe­ty pro­file.

Aca­dia aims to test the drug for MDD in a Phase III tri­al in the first half of 2019, and — to the sur­prise of an­a­lysts in a post-an­nounce­ment con­fer­ence call — sug­gest­ed the CLAR­I­TY tri­al would serve as one of two piv­otal tri­als re­quired to sub­mit a sup­ple­men­tal mar­ket­ing ap­pli­ca­tion for an MDD ap­proval.

Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology
ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development
CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

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Hal Barron. GSK

GSK's Hal Bar­ron her­alds their sec­ond pos­i­tive piv­otal for cru­cial an­ti-BC­MA ther­a­py, point­ing to a push for quick OKs in a crowd­ed field

Hal Barron has his second positive round of Phase III data in hand for his anti-BCMA antibody drug conjugate belantamab mafodotin (GSK2857916). And GSK’s research chief says the data paves the way for their drive in search of an FDA approval for treating multiple myeloma.

It’s hard to overestimate the importance of this drug for GSK, a cornerstone of Barron’s campaign to make a dramatic impact on the oncology market and provide some long-lost excitement for the pharma giant’s pipeline. They’re putting this BCMA program at the front of that charge — looking to lead a host of rivals all aimed at the same target.

We don’t know what the data are yet, but DREAMM-2 falls on the heels of a promising set of data delivered 5 months ago for DREAMM-1. There investigators noted that complete responses among treatment-resistant patients rose to 15% in the extra year’s worth of data to look over, with a median progression-free survival rate of 12 months, up from 7.9 months reported earlier. The median duration of response was 14.3 months.

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Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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Why would Am­gen want to buy Alex­ion? An­a­lysts call hot­ly ru­mored takeover un­like­ly, but seize the mo­ment

A rumor that Amgen is closing in on buyout deal for Alexion has sparked a guessing game on just what kind of M&A strategy Amgen is pursuing and how much Alexion is worth.

Mizuho analyst Salim Syed first lent credence to the report out of the Spanish news outlet Intereconomía, which said Amgen is bidding as much as $200 per share. While the source may be questionable, “the concept of this happening doesn’t sound too crazy to me,” he wrote.

FDA asks why No­var­tis took two months to launch for­mal in­ter­nal probe, af­ter AveX­is flagged da­ta ma­nip­u­la­tion

And the plot thickens. Novartis $NVS officials are reportedly now scrambling to explain to the FDA why it took them two months to open an internal investigation into data discrepancies for their $2.1 million gene-therapy for spinal muscular dystrophy — the world’s most expensive drug.

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Build­ing on suc­cess­ful PD-1 pact, Eli Lil­ly li­cens­es di­a­betes drug to Chi­nese part­ners at In­novent

Eli Lilly is expanding its partnership with China’s Innovent in a deal involving a diabetes drug sitting in its Phase I reserves.

The two companies had jointly developed one of China’s first homegrown PD-1 agents, scoring an approval for Tyvyt (sintilimab) late last year for relapsed/refractory classical Hodgkin’s lymphoma. This time around, Lilly is out-licensing a piece of its diabetes pipeline, a leading franchise that has historically produced the top-selling Trulicity and Humalog.

Am­gen, Al­ler­gan biosim­i­lar of Roche's block­buster Rit­ux­an clears an­oth­er US piv­otal study 

Novartis $NVS may have given up, but Amgen $AMGN and Allergan $AGN are plowing ahead with their knockoff of Roche’s blockbuster biologic Rituxan in the United States.

Their copycat, ABP 798, was found to have a clinically equivalent impact as Rituxan — meeting the main goal of the study involving CD20-positive B-cell non-Hodgkin’s lymphoma patients. This is the second trial supporting the profile of the biosimilar. In January, it came through with positive PK results in patients with rheumatoid arthritis.

Trump ad­min­is­tra­tion re­vives bid to get drug list prices on TV ads

The Trump administration is not giving up just yet. On Wednesday, the HHS filed an appeal against a judge’s decision in July to overturn a ruling obligating drug manufacturers to disclose the list price of their therapies in television adverts — hours before it was stipulated to go into effect.

In May, the HHS published a final ruling requiring drugmakers to divulge the wholesale acquisition cost— of a 30-day supply of the drug — in tv ads in a bid to enhance price transparency in the United States. The pharmaceutical industry has vehemently opposed the rule, asserting that list prices are not what a typical patient in the United States pays for treatment — that number is typically determined by the type of (or lack thereof) insurance coverage, deductibles and out-of-pocket costs. Although there is truth to that claim, the move was considered symbolic in the Trump administration’s healthcare agenda to hold drugmakers accountable in a climate where skyrocketing drug prices have incensed Americans on both sides of the aisle.