Fresh from a $72M raise, Jeff Aron­in's new lead rare dis­ease drug is flagged as a fail­ure

Just a few days af­ter one of Jeff Aronin’s biotechs put out the word that they had raised $71.8 mil­lion to push their rare dis­ease drug in­to piv­otal tri­als, the com­pa­ny qui­et­ly flagged the treat­ment’s fail­ure in Phase II.

But they are go­ing for Phase III any­way.

Jeff Aronin

The clin­i­cal­tri­ page on the Phase II study of Cas­tle Creek’s on­ly drug was up­dat­ed on Oc­to­ber 22 and now reads that the tri­al was ter­mi­nat­ed af­ter an in­de­pen­dent da­ta mon­i­tor­ing com­mit­tee “sug­gest­ed that the study will not meet sta­tis­ti­cal ob­jec­tives.” The page al­so in­cludes a time­line with a wrap due in the mid­dle of Oc­to­ber.

Cas­tle Creek’s co-founder, Michael Der­by, re­spond­ed to an email query of mine to say that the tri­al “showed sev­er­al pos­i­tive trends in key ef­fi­ca­cy mea­sures and a be­nign safe­ty pro­file that strong­ly sup­port con­tin­ued phase 3 de­vel­op­ment of this po­ten­tial treat­ment, which is our plan.”

He added:

The de­ci­sion to ter­mi­nate the phase 2 study was made fol­low­ing a planned in­ter­im analy­sis by an In­de­pen­dent Da­ta Mon­i­tor­ing Com­mit­tee that in­di­cat­ed that the tri­al, as struc­tured and pow­ered, was un­like­ly to de­liv­er the lev­el of sta­tis­ti­cal ro­bust­ness need­ed to con­firm ef­fi­ca­cy as de­fined by the pri­ma­ry end­point. In light of this da­ta, we plan to use our most re­cent in­vest­ment to pur­sue the late-stage de­vel­op­ment of this in­ves­ti­ga­tion­al drug. Giv­en the un­met med­ical need for pa­tients with EBS, we are al­so al­low­ing pa­tients from the ter­mi­nat­ed phase 2 tri­al to con­tin­ue ther­a­py in an on­go­ing open-la­bel ex­ten­sion tri­al.

To be clear, all of the in­vestors in Cas­tle Creek, in­clud­ing the in­vestors in our most re­cent fi­nanc­ing, were briefed on the in­ter­im re­sults and the de­ci­sion to ter­mi­nate the tri­al. They ful­ly sup­port our plan to con­tin­ue de­vel­op­ment and to de­sign an ad­e­quate­ly pow­ered phase 3 ef­fi­ca­cy and safe­ty tri­al.

Aronin — best known for kick­ing up a ruckus af­ter cob­bling to­geth­er da­ta on an old, cheap steroid sold over­seas for around $1,000 a year and steer­ing it through an FDA ap­proval for Duchenne mus­cu­lar dy­s­tro­phy with plans to sell it for $89,000 a year — runs Paragon Bio­sciences, which in turn owns 6 sub­sidiaries in­clud­ing Cas­tle Creek.

Michael Der­by

In Cas­tle Creek’s case, they took an old drug that is mar­ket­ed in a va­ri­ety of coun­tries around the world for os­teoarthri­tis — 50 mg di­ac­ere­in — and re­for­mu­lat­ed the IL-1 be­ta an­ti-in­flam­ma­to­ry drug in­to a top­i­cal treat­ment for an ul­tra-rare frag­ile skin dis­ease called epi­der­mol­y­sis bul­losa. 

Fi­deli­ty Man­age­ment & Re­search Com­pa­ny and Val­or Eq­ui­ty Part­ners put up the mon­ey to fund late-stage de­vel­op­ment.

Back in 2014 the EMA added re­stric­tions on the use of drugs con­tain­ing di­ac­ere­in, cit­ing ad­verse events that in­cludes prob­lems with the liv­er. The FDA, in turn, pro­vid­ed the com­pa­ny with a rare pe­di­atric dis­ease des­ig­na­tion for di­ac­ere­in 1% oint­ment, just as they did when Aronin was de­vel­op­ing his steroid Em­flaza. Those des­ig­na­tions are worth quite a bit, as an ap­proval would war­rant an award of a pri­or­i­ty re­view vouch­er worth more than $100 mil­lion.

And there are some dis­tinct sim­i­lar­i­ties be­tween his lat­est rare dis­ease pro­gram and his score on DMD, which a num­ber of harsh crit­ics in Con­gress con­clud­ed was re­ward­ed for a suc­cess­ful plan to game the drug ap­proval sys­tem.

Aronin has many of his old crew at Marathon — dis­band­ed in the wake of the con­tro­ver­sy over de­flaza­cort — work­ing at Paragon. The biotech proved to be an in­spi­ra­tion for Mar­tin Shkre­li, the phar­ma bro who was cas­ti­gat­ed when he en­gi­neered a 5,000%-plus overnight price hike at Tur­ing for an old drug of his own.

“These guys in­vent­ed price in­creas­es,” Shkre­li com­ment­ed once, be­fore he was sen­tenced to 7 years in a fed­er­al prison for de­fraud­ing in­vestors at his hedge funds. “I lit­er­al­ly learned it from them.”

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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UP­DAT­ED: Pay­back? An­a­lysts say Sarep­ta was blind­sided by an FDA re­jec­tion dri­ven by reg­u­la­to­ry re­venge

In one of the least anticipated moves of the year, the FDA has rejected Sarepta’s application for an accelerated approval of its Duchenne MD drug golodirsen after fretting over safety issues.

In a statement that arrived after the bell on Monday, Sarepta explained the CRL, saying:

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FDA de­ci­sion on Ver­tex's CF triple will come just ahead of planned CEO shake­up

Vertex has clinched a priority review for the all-important cystic fibrosis triple that will blaze the trail for treating a large group of patients unhelped by its current drugs.

FDA regulators have set a PDUFA date of March 19, 2020, just a year after the Boston biotech posted positive Phase III results showing that people with two F508del mutations experienced statistically significant improvements in lung function after a 4-week regimen of VX-445, tezacaftor and ivacaftor. After reviewing 24-week data among patients with one F508del mutation and one minimal function mutation — and thoroughly comparing the VX-445 triple with another combo featuring VX-659 on scores like safety, drug-drug interactions, and photosensitivity — Vertex ultimately went with VX-445.

An MIT spin­out kills one of its ‘liv­ing ther­a­peu­tics’ af­ter flunk­ing an ear­ly-stage study — shares rout­ed

Just a few weeks after bagging $80 million in a deal to collaborate with Gingko Bioworks on its special blend of engineered bacteria used for “living therapeutics,” little Synlogic in Boston $SYBX is tossing one of its two clinical programs after watching an early-stage study go down in defeat.

Their Phase Ib/IIa study for SYNB1020 to counter the accumulation of ammonia in the body, a condition called hyperammonemia or urea cycle disorder, floundered at the interim readout, forcing the biotech to kill it and reserve its cash for pipeline therapies with greater potential.

Elan­co to buy Bay­er's an­i­mal health busi­ness for $7.6B, as deal­mak­ing gath­ers steam in the sec­tor

Last week, Elanco explicitly dodged answering questions about its rumored interest in Bayer’s animal health business in its post-earnings call. On Tuesday, the Eli Lilly spinoff disclosed it was purchasing the German drug maker’s veterinary unit in a cash-and-stock deal worth $7.6 billion. 

Elanco $ELAN has been busy on the deal-making front. In April, it laid out plans to swallow its partner, Kansas-based pet therapeutics company Aratana $PETX. A July report by Reuters suggested a potential Bayer deal was being explored, and Bloomberg last week said the deal was imminent, citing sources. 

As­traZeneca's di­a­betes drug Farx­i­ga helps pa­tients with heart dis­ease and with­out di­a­betes in land­mark tri­al

Months ago, data on J&J’s $JNJ Invokana indicated the diabetes drug conferred cardiovascular (CV) benefit in patients who do and do not have preexisting CV disease. On Tuesday, AstraZeneca’s $AZN rival treatment, Farxiga, was shown to cut the risk of CV death or the worsening of heart failure in patients with heart disease, in a landmark trial.

The treatments, in addition to Jardiance from Eli Lilly $LLY, belong to a class of diabetes drugs called sodium-glucose co-transporter 2 (SGLT2) inhibitors, which work by curbing the absorption of glucose via the kidneys so that surplus glucose is excreted through urination.

Levi Garraway. Broad Institute via Youtube

Roche raids Eli Lil­ly for its next chief med­ical of­fi­cer as San­dra Horn­ing plans to step down

We found out Monday morning where Levi Garraway was headed after he left Eli Lilly as head of oncology R&D a few days ago. Roche named Garraway as their new chief medical officer, replacing Sandra Horning, who they say is retiring from the company.

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Af­ter a posse of Wall Street an­a­lysts pre­dict a like­ly new win for Sarep­ta, we're down to the wire on a crit­i­cal FDA de­ci­sion

As Bloomberg notes, most of the Wall Street analysts that cover Sarepta $SRPT are an upbeat bunch, ready to cheer on the team when it comes to their Duchenne MD drugs, or offer explanations when an odd setback occurs — as happened recently with a safety signal that was ‘erroneously’ reported last week.

Ritu Baral Cowen
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