In a damn­ing in­dict­ment, FDA re­view scorns PTC’s Duchenne drug for re­peat­ed fail­ures

PTC Ther­a­peu­tics $PTCT ex­ec team proved this week that they are glut­tons for pun­ish­ment.

PTC Ther­a­peu­tics CEO Stu­art Peltz

Af­ter en­dur­ing two hu­mil­i­at­ing slap-downs at the FDA for their would-be Duchenne drug ataluren, the biotech — led by CEO Stu­art Peltz — has forced the agency’s hand, re­quir­ing a pan­el re­view on Thurs­day. And in the agency’s re­view of the drug, re­leased Tues­day morn­ing, the FDA went to con­sid­er­able lengths to ex­plain why they think this drug — pro­vid­ed an ac­cel­er­at­ed ap­proval in Eu­rope, where it’s sold to pa­tients as Translar­na — has re­peat­ed­ly proved to be un­wor­thy of an ap­proval.

PTC shares slid 23% af­ter the re­view land­ed, prov­ing that there are still clear lines on ef­fi­ca­cy that the FDA will not cross.

The sum­ma­ry says it all. Reg­u­la­tors at the FDA re­it­er­at­ed a se­ries of damn­ing con­clu­sions, with no pos­i­tive da­ta to con­sid­er. PTC’s post hoc analy­ses of failed stud­ies, they con­clud­ed, are un­con­vinc­ing in light of the fact that the re­sults were “clear­ly neg­a­tive”, while high­light­ing the “mis­lead­ing na­ture of ex­plorato­ry analy­ses of neg­a­tive tri­als.” And there’s no rea­son to be­lieve that any fu­ture tri­als of this drug will prove it can be ef­fec­tive.

In full, the FDA stat­ed:

Ul­ti­mate­ly, no pos­i­tive re­sults from any prospec­tive­ly planned analy­ses that are per­sua­sive have been pro­vid­ed with this ap­pli­ca­tion. The ap­pli­cant has pre­sent­ed on­ly the re­sults from nu­mer­ous post hoc and ex­plorato­ry analy­ses that are in­tend­ed to mit­i­gate two neg­a­tive clin­i­cal tri­als. In 2011, the ap­pli­cant claimed that the ef­fec­tive­ness of ataluren had been es­tab­lished based on the post hoc analy­ses of the ADP pop­u­la­tion in Study 007. How­ev­er, when this con­clu­sion was prospec­tive­ly eval­u­at­ed in Study 020, the re­sults were clear­ly neg­a­tive. This find­ing di­rect­ly high­lights the fre­quent­ly mis­lead­ing na­ture of ex­plorato­ry analy­ses of neg­a­tive tri­als. It is ar­guable that some trends ob­served in the ap­pli­cant’s da­ta may war­rant fur­ther prospec­tive in­ves­ti­ga­tion, which the Agency has con­sis­tent­ly en­cour­aged the ap­pli­cant to con­sid­er. Even so, for the rea­sons dis­cussed above, it seems quite pos­si­ble that any fu­ture study de­signed based on ex­plorato­ry analy­ses of Study 020 will al­so turn out to be neg­a­tive, just as Study 020, which was based on ex­plorato­ry post hoc analy­ses from Study 007, was neg­a­tive. The anal­o­gous re­sults from the ap­pli­cant’s de­vel­op­ment of ataluren for the treat­ment of nm­CF of­fer a sim­i­lar cau­tion­ary tale. Over­all, the da­ta in­tend­ed by the ap­pli­cant to es­tab­lish the ef­fec­tive­ness of ataluren for the treat­ment of nmD­MD are not per­sua­sive.

That qual­i­fies as one of the most con­clu­sive re­jec­tions I’ve seen of any drug ap­pli­ca­tion at the FDA. Pos­si­bly PTC was em­bold­ened by the agency’s ac­cel­er­at­ed OK of Sarep­ta’s drug, even though the com­pa­ny nev­er pro­vid­ed da­ta that the drug could work. In this case, though, the agency feels they have plen­ty of da­ta to con­clude that ataluren doesn’t work. And there’s no ev­i­dence to sug­gest that Janet Wood­cock will be rid­ing to PTC’s de­fense. Even a big show­ing of sup­port from Duchenne par­ents Thurs­day may prove un­like­ly to tip the scales in PTC’s fa­vor.

PTC, though, con­tin­ues to push ahead in DMD, re­gard­less of the crit­i­cism that has been lev­eled against it. That was proved again af­ter the com­pa­ny bought out  a cheap, old Eu­ro­pean steroid — de­flaza­cort — from Marathon Phar­ma­ceu­ti­cals af­ter Marathon ex­ecs de­cid­ed to bag it and flee from the in­tense re­ac­tion to their plans to price it at $89,000 list af­ter gain­ing the agency’s OK. PTC is now sell­ing de­flaza­cort at an even high­er rate for some of the old­er, larg­er boys suf­fer­ing from DMD af­ter par­ents had been able to source it abroad for about $1,000 a year.

Eu­ro­pean reg­u­la­tors have re­peat­ed­ly giv­en PTC a pass with their drug. And there’s no in­di­ca­tion that even a damn­ing re­sponse like this will change their po­si­tion.

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 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.