Ax­o­van­t's lead Alzheimer's drug flops in PhI­II, end­ing an un­like­ly quest

Vivek Ra­maswamy burst on­to the biotech scene a few years ago with a brash plan to grab a failed drug from Glax­o­SmithK­line and hus­tle it straight in­to a piv­otal Phase III study for Alzheimer’s — a dis­ease that has de­feat­ed every piv­otal shot tak­en at it over the past 15 years.

But in­tepir­dine, like every oth­er Phase III Alzheimer’s study, failed. And this fail­ure for Ra­maswamy’s Ax­o­vant will like­ly kill 5HT6 as a tar­get in Alzheimer’s af­ter sev­er­al oth­er stud­ies with the same tar­get al­so flopped over the past year.

The news quick­ly crushed Ax­o­vant’s share price, send­ing it down more than 70% and wip­ing out $1.8 bil­lion in mar­ket cap in sec­onds as in­vestors re­act­ed to one of the biggest cat­a­lysts of the month.

Re­searchers said that the drug failed both co-pri­ma­ry end­points, un­able to sig­nif­i­cant­ly im­prove cog­ni­tion or func­tion for pa­tients rel­a­tive to place­bo. The key num­bers: ADAS-Cog (0.36 points, p=0.22) and AD­CS-ADL (0.09, p=0.83).

The com­pa­ny is stick­ing with top-line da­ta for now, plan­ning to out­line more of the specifics at an up­com­ing con­fer­ence. But in a call with an­a­lysts Tues­day, Ax­o­vant CEO David Hung made it clear that the drug com­bined with donepezil failed bad­ly.

“There was no dif­fer­ence be­tween the in­tepir­dine and the place­bo arms,” said Hung, and the Alzheimer’s pro­gram is fin­ished — though the com­pa­ny plans to pur­sue its work on de­men­tia with Lewy bod­ies.

The fail­ure here will come as no sur­prise to long­time in­ves­ti­ga­tors in the field. Pfiz­er and Lund­beck had both tried and failed to amp up cog­ni­tion with a 5HT6 pro­gram, de­signed to spur re­lease of a neu­ro­trans­mit­ter, though Ax­o­vant in­sist­ed that it could beat the odds.

If it had, an­a­lysts agreed that a new drug now could be worth bil­lions in an­nu­al rev­enue. In­stead, the drug hasn’t proven it’s worth the $5 mil­lion Ra­maswamy paid for it.

“While we are deeply dis­ap­point­ed by these tri­al re­sults, we al­so are sad­dened for the mil­lions of pa­tients and fam­i­lies im­pact­ed by Alzheimer’s dis­ease. How­ev­er, we be­lieve that the fight against Alzheimer’s and oth­er im­por­tant ar­eas of un­met need in neu­rol­o­gy is too im­por­tant to be de­railed by this set­back,” said Hung in a state­ment.

While the drug cost on­ly a few mil­lion up front to li­cense, the 32-year-old Ra­maswamy quick­ly steered Ax­o­vant $AX­ON in­to a record-set­ting biotech IPO on this drug, on his way to gath­er­ing close to $2 bil­lion to back a mul­ti-faceted en­ter­prise that has grown rapid­ly. He was able to re­cruit CEO Hung to take the helm not long af­ter Hung com­plet­ed the deal of a life­time in sell­ing Medi­va­tion to Pfiz­er for $14 bil­lion.

For Hung, it was a chance to take an­oth­er shot at Alzheimer’s, a dis­ease that had de­feat­ed one of his can­di­dates at Medi­va­tion.

Ra­maswamy had in­sist­ed that this drug would prove dif­fer­ent, point­ing to tri­al da­ta that showed a path for­ward. In­tepir­dine was his first test of a busi­ness mod­el that de­pends on gain­ing ac­cess to drugs on the shelves at the world’s biggest phar­ma com­pa­nies. But that mod­el faces fresh ques­tions this morn­ing as Ax­o­vant and the par­ent com­pa­ny — Roivant — deal with a bit­ter set­back.

Roivant put out a state­ment this morn­ing point­ing to all the oth­er drugs now in its mul­ti­ple pipelines. Ax­o­vant, the com­pa­ny not­ed, will con­tin­ue to in­ves­ti­gate new drugs for the mem­o­ry wast­ing ail­ment, just as it will con­tin­ue to go af­ter oth­er drugs. And with­out at­tri­bu­tion, the com­pa­ny says it will per­se­vere.

Some of those ef­forts will suc­ceed. Oth­ers will fail. We owe it to pa­tients to take those risks, and we re­main un­de­terred in pur­su­ing our mis­sion.


Im­age: Vivek Ra­maswamy Get­ty, David Hung File Pho­to

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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Hal Barron. GSK

GSK's Hal Bar­ron her­alds their sec­ond pos­i­tive PhI­II 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.

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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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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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

Am­gen, Al­ler­gan biosim­i­lar of Roche's block­buster Rit­ux­an clears an­oth­er US piv­otal study 

Novartis $NVS may have given up, but Amgen $AMGN and Allergan $AGN are plowing ahead with their knockoff of Roche’s blockbuster biologic Rituxan in the United States.

Their copycat, ABP 798, was found to have a clinically equivalent impact as Rituxan — meeting the main goal of the study involving CD20-positive B-cell non-Hodgkin’s lymphoma patients. This is the second trial supporting the profile of the biosimilar. In January, it came through with positive PK results in patients with rheumatoid arthritis.

BeiGene and Mus­tang nail down spe­cial FDA sta­tus for top drugs; Roche bags added cov­er­age for Hem­li­bra

→ BeiGene $BGNE is getting a boost in its drive to field a rival to Imbruvica. The FDA has offered an accelerated review to zanubrutinib, a BTK inhibitor that has posted positive results for mantle cell lymphoma. The PDUFA date lands on February 27, 2020. The drug scored breakthrough status at the beginning of the year.

→ BeiGene isn’t the only biopharma company to gain special regulatory status today. Mustang Bio $MBIO and St. Jude Children’s Research Hospital announced that MB-107, a lentiviral gene therapy for the treatment of X-linked severe combined immunodeficiency, also known as bubble boy disease, has been granted Regenerative Medicine Advanced Therapy status.