Point­ing to a cure, Bio­Marin re­ports im­pres­sive tri­al re­sults for he­mo­phil­ia A gene ther­a­py

Bio­Marin says it nailed down hard ev­i­dence that its gene ther­a­py for he­mo­phil­ia A demon­strat­ed a high chance of restor­ing pa­tients’ nat­ur­al clot­ting abil­i­ties, re­duc­ing or elim­i­nat­ing bleed­ing episodes and point­ing them down the road to a nor­mal life. And com­pa­ny $BM­RN in­ves­ti­ga­tors say they are now hus­tling BMN 270 in­to a Phase IIb study that could be used to gain an ac­cel­er­at­ed ap­proval for a po­ten­tial block­buster.

Nine pa­tients re­ceived a sin­gle treat­ment with the gene ther­a­py, 7 at the high­est dose. The treat­ment us­es a be­nign vi­ral vec­tor to de­liv­er a miss­ing gene need­ed to pro­duce fac­tor VI­II, which is re­quired to spur clot­ting. The da­ta were pre­sent­ed at the an­nu­al meet­ing of the World Fed­er­a­tion of He­mo­phil­ia. Bio­Marin not­ed that:

(S)ix of sev­en pa­tients had Fac­tor VI­II lev­els above 50%, as a per­cent­age cal­cu­lat­ed based on the num­bers of In­ter­na­tion­al Units per deciliter of plas­ma (IU/dL), and the sev­enth was above 10%. In ad­di­tion, four pa­tients who have been fol­lowed the longest had a mean Fac­tor VI­II lev­el of 146% at their 20 week vis­it. Two pa­tients with Fac­tor VI­II lev­els above 200% had no un­ex­pect­ed events or need for med­ical in­ter­ven­tion. For the sev­en pa­tients at the high dose, the me­di­an an­nu­al­ized bleed­ing rate mea­sured from day of gene trans­fer to da­ta cut of ob­ser­va­tion pe­ri­od fell to 5 from 20.

In ad­di­tion, the in­ves­ti­ga­tors re­port­ed no se­ri­ous safe­ty is­sues in the study, with pa­tients ta­per­ing off steroid use with­out the kind of liv­er tox is­sues that could scut­tle the work.

Hen­ry Fuchs, CMO at Bio­Marin

The re­sults from the study were “way be­yond our dreams and ex­pec­ta­tions,” says Hank Fuchs, the chief med­ical of­fi­cer at Bio­Marin, cit­ing the in­ves­ti­ga­tors and on­look­ers who have been track­ing this study.

This is the on­ly he­mo­phil­ia A pro­gram in the clin­ic that Fuchs knows of, and he tells me that the once-off ther­a­py “has the po­ten­tial to change peo­ple’s lives.”

“We have con­sid­er­able in­ter­est in mov­ing quick­ly,” adds the R&D chief, adding that the com­pa­ny wants to pre­serve its lead. But he’s not quite ready to say when the com­pa­ny will have the da­ta from the next study need­ed to pur­sue a fast ap­proval.

Shares of Bio­Marin, which has tapped this ther­a­py as one of its top prospec­tive pro­grams in the pipeline, spiked 6% on the news Wednes­day af­ter­noon.

That amounts to a big win for Bio­Marin, which has been buf­fet­ed by re­cent set­backs, in­clud­ing the FDA’s re­jec­tion of its Duchenne mus­cu­lar dy­s­tro­phy drug dris­apersen. Bio­Marin scrapped that pro­gram and three oth­ers af­ter the EMA al­so scorned its ap­pli­ca­tion.

There are a num­ber of gene ther­a­py pro­grams in the works for he­mo­phil­ia, in­clud­ing one at Bio­gen $BI­IB. Spark Ther­a­peu­tics $ONCE, which has the most ad­vanced gene ther­a­py pro­gram in the U.S., has a pre­clin­i­cal pro­gram for he­mo­phil­ia A and a clin­i­cal ef­fort un­der­way for he­mo­phil­ia B; same for uniQure $QURE. And Sang­amo $SG­MO just pre­sent­ed pre­clin­i­cal ev­i­dence to back its pro­gram.

“These da­ta pro­vide strong proof of con­cept ev­i­dence that restora­tion of clot­ting func­tion may be achieved by gene ther­a­py,” said John Pasi, a pro­fes­sor of haemosta­sis and throm­bo­sis at Barts and the Lon­don School of Med­i­cine and Den­tistry and pri­ma­ry in­ves­ti­ga­tor for the BMN 270 Phase 1/2 clin­i­cal tri­al.  “For the first time, pa­tients have rea­son to hope to avoid bleed­ing and the op­por­tu­ni­ty to live a nor­mal life.”

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.