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 clin­i­cal­tri­als.gov 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.”

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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Vicente Anido (University of West Virginia via YouTube)

Aerie fires CEO af­ter lead pro­gram flop, com­ments about pri­ma­ry end­points be­ing 'not re­quired'

Aerie Pharmaceuticals CEO Vicente Anido has left the company less than a week after trying to chart a Phase III study in the wake of a serious Phase IIb flop.

Anido’s last day at Aerie was Friday, the biotech announced in a news release Tuesday morning, and Benjamin McGraw is taking his place in an interim role. The now former CEO was terminated without cause, according to an SEC filing.

The board has started looking for a full-time chief to take his place.

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When ef­fi­ca­cy is bor­der­line: FDA needs to get more con­sis­tent on close-call drug ap­provals, agency-fund­ed re­search finds

In the exceedingly rare instances in which clinical efficacy is the only barrier to a new drug’s approval, new FDA-funded research from FDA and Stanford found that the agency does not have a consistent standard for defining “substantial evidence” when flexible criteria are used for an approval.

The research comes as the FDA is at a crossroads with its expedited-review pathways. The accelerated approval pathway is under fire as the agency recently signed off on a controversial new Alzheimer’s drug, with little precedent to explain its decision. Meanwhile, top officials like Rick Pazdur have called for a major push to simplify and clarify all of the various expedited pathways, which have grown to be must-haves for sponsors of nearly every newly approved drug.

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Ted White, Verrica CEO

Ver­ri­ca hits an­oth­er bump in the road with CMO re­lat­ed let­ter from FDA

The FDA has rejected Verrica’s new drug application for VP-102 again, with the company pinning the CRL on problems at a CMO that it was partnered with, the company announced Monday.

The FDA didn’t raise issues that directly relate to the manufacturing of VP-102, the company said, but raised “general quality issues” at the CMO’s facility. There were also no clinical concerns, it said, or need to collect more data.

Take­da snaps up the Japan­ese rights to an old Shire cast-off; Boehringer In­gel­heim ac­quires Abexxa Bi­o­log­ics

A week before the FDA is set to decide on Mirum Pharmaceuticals’ lead liver disease drug — an old Shire cast-off called maralixibat — Takeda is swooping in to secure the rights in Japan.

Maralixibat’s roots trace back to Lumena, which was snapped up by Shire for $260 million-plus back in 2014. While the candidate had failed mid-stage studies at Shire, Mirum believes better trial design and patient selection will deliver the wins it needs. The drug is currently in development for Alagille syndrome (a condition called ALGS in which bile builds up in the liver), progressive familial intrahepatic cholestasis (PFIC, which causes progressive liver disease) and biliary atresia (a blockage in the ducts that carry bile from the liver to the gallbladder).

Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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