Ver­tex shut­ters a PhI­II cys­tic fi­bro­sis com­bo study, shares slip

Shares of Ver­tex slid Mon­day af­ter­noon af­ter the com­pa­ny said it will scrap one of its late-stage stud­ies for a com­bi­na­tion ther­a­py for cys­tic fi­bro­sis af­ter it failed to pass muster in a fu­til­i­ty analy­sis.

Ver­tex $VRTX is halt­ing its study of VX-661 and Ka­ly­de­co (iva­caftor) in peo­ple with one copy of the F508del mu­ta­tion and one copy of a mu­ta­tion that re­sults in min­i­mal CFTR pro­tein func­tion (F508del het/min). The study stum­bled in its first phase, with­out an im­prove­ment in lung func­tion.

Shares of Ver­tex slipped 3.4% on the news.

That het/min tar­get rep­re­sent­ed the largest mar­ket op­por­tu­ni­ty for Ver­tex with VX-661, ac­cord­ing to a note from Leerink’s Ge­of­frey Porges this morn­ing. But Porges al­so called it the least like­ly of the four tri­als to suc­ceed. Even so, the re­main­ing late-stage stud­ies in the VX-661 stud­ies of­fer a sub­stan­tial mar­ket op­por­tu­ni­ty. Notes Porges:

Our analy­sis and con­ver­sa­tions with MEDA­Corp spe­cial­ists sug­gest that Vx-661/Ka­ly­de­co could gen­er­ate an im­prove­ment in ppFEV1 in the range of 4-5% in the ho­mozy­gous delF508 pa­tients, com­pared to Orkam­bi’s 2-3%, with greater ef­fects on hos­pi­tal­iza­tions and ex­ac­er­ba­tions as well; Vx-661 should be eas­i­er to take (less drug-drug in­ter­ac­tions, less tol­er­a­bil­i­ty and meta­bol­ic ef­fects) and have more ef­fect than Orkam­bi; this suc­cess should trans­late in­to in­cre­men­tal rev­enue po­ten­tial that we es­ti­mate to be in the range of ~$485mm, as­sum­ing com­pa­ra­ble pric­ing to Orkam­bi in all mar­kets.

Ver­tex Chief Med­ical Of­fi­cer Jef­frey Chodake­witz

“While we rec­og­nize that peo­ple with CF with min­i­mal func­tion mu­ta­tions have a form of the dis­ease that is par­tic­u­lar­ly dif­fi­cult to treat, we be­lieved it was im­por­tant to eval­u­ate whether a dual com­bi­na­tion of VX-661 and iva­caftor could pro­vide some ben­e­fit to these pa­tients giv­en they do not to­day have a med­i­cine to treat the cause of their dis­ease,” said Ver­tex Chief Med­ical Of­fi­cer Jef­frey Chodake­witz. “These re­sults sug­gest that a triple com­bi­na­tion reg­i­men may pro­vide this group of peo­ple with CF the best chance at ob­tain­ing a mean­ing­ful ben­e­fit and we look for­ward to be­gin­ning the first study of a next-gen­er­a­tion cor­rec­tor to­geth­er with VX-661 and iva­caftor in this group of pa­tients lat­er this year, pend­ing da­ta from our on­go­ing Phase 1 stud­ies in healthy vol­un­teers.”

VX-661 is Ver­tex’s sec­ond-gen cor­rec­tor, a suc­ces­sor to the first-gen cor­rec­tor lumacaftor, in­clud­ed in the drug com­bi­na­tion for Orkam­bi. Two third-gen cor­rec­tors, VX-152 and VX-440, have been in ear­ly-stage stud­ies as Ver­tex plumbs new ap­proach­es that can treat CF bet­ter than Orkam­bi, which has suf­fered a high dropout rate. The treat­ment tar­gets the un­der­ly­ing ge­net­ic cause of the dis­ease.

The VX-661 pro­gram in­cludes four Phase III stud­ies in mul­ti­ple dif­fer­ent groups of peo­ple with CF who have at least one copy of the F508del mu­ta­tion.

Ver­tex has a $25.4 bil­lion mar­ket cap.

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.