Prothena care­ful­ly ex­plains why it's killing a pso­ri­a­sis drug af­ter PhIb

Sarah Noon­berg

Prothena is cut­ting its loss­es on one of its key drug de­vel­op­ment pro­grams af­ter con­clud­ing their ther­a­py failed to pass muster in a Phase Ib study of pso­ri­a­sis.

PRX003 hit its mark — CD146 — on Th17 cells, as they ex­pect­ed. But re­searchers didn’t see the kind of phar­ma­co­dy­nam­ic ef­fect they were look­ing for. So there will be no Phase II to come in ei­ther pso­ri­a­sis or atopic der­mati­tis, two ail­ments which have seen con­sid­er­able progress re­cent­ly from new­ly ap­proved ther­a­pies.

To their cred­it, ex­ecs at Dublin-based Prothena $PR­TA were un­sen­ti­men­tal in their eval­u­a­tion of the re­sults. And for a small study with 33 pa­tients di­vid­ed be­tween a va­ri­ety of dos­es and a place­bo arm, Prothena gath­ered con­sid­er­able knowl­edge from the study.

The biotech’s stock dipped 6% on the news in af­ter-mar­ket trad­ing.

This seg­ment is worth read­ing:

Across all PRX003 dose lev­els in the Phase 1b MAD study, no clin­i­cal­ly rel­e­vant or sta­tis­ti­cal­ly sig­nif­i­cant ben­e­fit on PASI 75 re­sponse was ob­served. At week 12, 29 per­cent of PRX003-treat­ed pa­tients (2 out of 7) in the 1 mg/kg dose co­hort achieved a PASI 75 re­sponse  (p=0.2 rel­a­tive to place­bo), and no pa­tients in the 3 mg/kg, 10 mg/kg or 30 mg/kg dose co­horts achieved a PASI 75 re­sponse. Eval­u­a­tion of Th17 cell mi­gra­tion re­vealed in­suf­fi­cient de­creas­es in Th17 cell in­fil­tra­tion in­to tis­sue. Ad­di­tion­al­ly, as mea­sured from skin biop­sies there were no clin­i­cal­ly mean­ing­ful or dose-de­pen­dent changes in RNA tran­script lev­els of genes as­so­ci­at­ed with Th17-me­di­at­ed in­flam­ma­tion, in­clud­ing IL-17A, IL-17F, IL-6, TN­Fα, and IFNγ. De­spite mod­est ev­i­dence of a clin­i­cal ef­fect on PASI 75 re­sponse at the low­est dose lev­el, there was no re­la­tion­ship be­tween dose lev­els, RNA tran­script lev­els or oth­er mark­ers of in­flam­ma­to­ry ac­tiv­i­ty that pro­vid­ed ev­i­dence of a mean­ing­ful ther­a­peu­tic ef­fect. Col­lec­tive­ly, these da­ta demon­strat­ed that near-com­plete down­reg­u­la­tion of CD146 is in­suf­fi­cient to in­hib­it Th17 cell in­fil­tra­tion and as­so­ci­at­ed in­flam­ma­tion to the de­gree nec­es­sary to achieve mean­ing­ful clin­i­cal ben­e­fit in pa­tients with pso­ri­a­sis.

CEO Gene Kin­ney says the fo­cus now is on NEOD001 (Phase IIb and Phase III), PRX002 (Phase I) and PRX004 (ex­pect­ed to en­ter Phase I by mid-2018).

CEO Gene Kin­ney

“While we ob­served oc­cu­pan­cy and down­reg­u­la­tion of CD146 fol­low­ing ad­min­is­tra­tion of PRX003 con­sis­tent with our pre­vi­ous Phase 1a SAD study, the clin­i­cal re­sults in this study did not meet our pre-spec­i­fied cri­te­ria for ev­i­dence of a well-de­fined re­la­tion­ship be­tween bi­o­log­i­cal ac­tiv­i­ty and mean­ing­ful clin­i­cal ef­fects re­quired to ad­vance PRX003 in­to mid-stage clin­i­cal de­vel­op­ment for pso­ri­a­sis or pso­ri­at­ic arthri­tis as pre­vi­ous­ly planned,” said Sarah Noon­berg, chief med­ical of­fi­cer of Prothena. “More­over, these re­sults in­di­cate the need for a deep­er un­der­stand­ing of CD146 mod­u­la­tion in the treat­ment of com­plex dis­ease states. We want to thank the pa­tients, clin­i­cians and site co­or­di­na­tors who have helped us ex­e­cute this thor­ough study.”

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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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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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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UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

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Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll

As­traZeneca’s Imfinzi/treme com­bo strikes out — again — in lung can­cer. Is it time for last rites?

AstraZeneca bet big on the future of their PD-L1 Imfinzi combined with the experimental CTLA-4 drug tremelimumab. But once again it’s gone down to defeat in a major Phase III study — while adding damage to the theory involving targeting cancer with a high tumor mutational burden.

Early Wednesday the pharma giant announced that their NEPTUNE study had failed, with the combination unable to beat standard chemo at overall survival in high TMB cases of advanced non-small cell lung cancer. We won’t get hard data until later in the year, but the drumbeat of failures will call into question what — if any — future this combination can have left.

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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.