Once scored as a po­ten­tial block­buster, No­var­tis’ sere­lax­in fiz­zles in crit­i­cal car­dio out­comes test

Vas­ant Narasimhan

You can scratch sere­lax­in off No­var­tis’ list of po­ten­tial block­busters in the late-stage pipeline.

This morn­ing the phar­ma gi­ant said that its 4-year study of the heart drug flubbed the pri­ma­ry end­point, fail­ing to sig­nif­i­cant­ly cut the rate of car­dio­vas­cu­lar death or re­duce wors­en­ing heart fail­ure among pa­tients with acute heart fail­ure.

No­var­tis Chief Med­ical Of­fi­cer Vas Narasimhan said that the phar­ma gi­ant will con­tin­ue to look over the da­ta to de­ter­mine next steps. But the R&D jour­ney would ap­pear to be over.

De­spite win­ning one of the first break­through drug des­ig­na­tions at the FDA for this pro­gram, an FDA pan­el wasn’t per­suad­ed by the da­ta that No­var­tis of­fered. The agency for­mal­ly re­ject­ed the drug in the spring of 2014, look­ing for the out­comes da­ta from the 6,600 pa­tients re­cruit­ed for RE­LAX-AHF-2.

The EU fol­lowed up soon af­ter with a thumbs down as well.

No­var­tis ex­ecs had been con­vinced that sere­lax­in would be the next big thing in heart drugs, set on a course to block­buster sta­tus. The da­ta, how­ev­er, wouldn’t co­op­er­ate with their plans. And Leerink’s Sea­mus Fer­nan­dez was ready with last rites:

Giv­en the post-hoc na­ture of the pre­vi­ous analy­ses, rel­a­tive­ly small num­ber of clin­i­cal events, and lack of his­tor­i­cal suc­cess for oth­er agents in large acute HF tri­als, we had pre­vi­ous­ly been cau­tious on the chances for a fa­vor­able ben­e­fit on mor­tal­i­ty out­comes. Ac­cord­ing to pre­vi­ous dis­cus­sions with MEDA­Corp KOLs, suc­cess in this tri­al would have cre­at­ed a strong eth­i­cal man­date for use; how­ev­er we be­lieve the fail­ure es­sen­tial­ly ter­mi­nates all en­thu­si­asm for the drug.

The lat­est and per­haps last set­back on this drug leaves No­var­tis’ car­dio di­vi­sion de­pen­dent on En­tresto for its fu­ture. That drug has jumped off to a slow start, though, leav­ing an­a­lysts scratch­ing their heads over the drug’s po­ten­tial earn­ings.

En­tresto earned just $170 mil­lion last year, de­spite the com­pa­ny’s com­mit­ment to pay-for-per­for­mance con­tracts and a re­lent­less ef­fort to build the da­ta and pay­er deals need­ed to make the drug a suc­cess. Pay­ers, though, have their own ideas on how to han­dle a drug like this. They erect­ed bar­ri­ers with high co-pays and pri­or au­tho­riza­tion de­mands that made the drug hard to get. As Am­gen and the Re­gen­eron/Sanofi team found out the hard way with PC­SK9 drugs, try­ing to mar­ket a new drug aimed at heart dis­ease can be a dev­il­ish­ly dif­fi­cult task.

That kind of re­sis­tance will make it in­creas­ing­ly hard for large play­ers to tack­le the big and ex­pen­sive late-stage ef­forts that are need­ed to get these drugs across the fin­ish line. Sere­lax­in may ul­ti­mate­ly ex­er­cise ex­act­ly the op­po­site kind of in­flu­ence that No­var­tis was look­ing for.

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.