A for­mer fail­ure in PhII, the go-go FDA says it’s ready to con­sid­er an ac­cel­er­at­ed short­cut for Ul­tragenyx's UX007

More than a year af­ter Ul­tragenyx $RARE an­nounced the fail­ure of a Phase II study for its seizure med­ica­tion UX007, the rare dis­ease spe­cial­ist says the FDA has now of­fered a thumbs-up for its will­ing­ness to con­sid­er an ac­cel­er­at­ed ap­proval for a dif­fer­ent in­di­ca­tion.

The biotech is pur­su­ing an OK for long-chain fat­ty acid ox­i­da­tion dis­or­ders af­ter piec­ing to­geth­er da­ta that spot­light­ed a drop in ma­jor clin­i­cal events for LC-FAOD.

As the com­pa­ny ex­plains, LC-FAOD rep­re­sents “a group of au­to­so­mal re­ces­sive ge­net­ic dis­or­ders char­ac­ter­ized by meta­bol­ic de­fi­cien­cies in which the body is un­able to con­vert long-chain fat­ty acids in­to en­er­gy.” With­out that, there’s a se­vere de­ple­tion of glu­cose that can cause hav­oc in a child. It’s cur­rent­ly treat­ed with an ul­tra-low carb ke­to­genic di­et, which is a com­mon ther­a­py for epilep­sy and seizures, where Ul­tragenyx orig­i­nal­ly looked for pos­i­tive da­ta.

An­a­lysts at JMP Se­cu­ri­ties not­ed a few days ago that in their con­ver­sa­tions with Ul­tragenyx ex­ecs, they made it clear that reg­u­la­tors had al­ready de­ter­mined the biotech’s mid-stage da­ta were “con­found­ed and not suf­fi­cient to pur­sue a fil­ing.”

Now, sud­den­ly, that’s all changed.

This ac­cel­er­ates our launch time­lines. Pre­vi­ous­ly, we con­ser­v­a­tive­ly mod­eled a U.S. launch in 2021 which we now be­lieve could come as ear­ly as 2020. Ul­tragenyx an­tic­i­pates a pre-NDA meet­ing in 2H18 af­ter which it will pro­vide ad­di­tion­al de­tails; in the mean­time, we es­ti­mate a sub­mis­sion in 1H2019.

Emil Kakkis, Ul­tragenyx

The ear­li­er mid-stage fail­ure was plain. UX007 is a drug de­signed to ad­dress glu­cose trans­porter type-1 de­fi­cien­cy syn­drome — or Glut1 DS — in chil­dren by get­ting glu­cose in­to the brains of the ge­net­i­cal­ly af­flict­ed group. With­out the right lev­el of glu­cose, pa­tients have a ten­den­cy to ex­pe­ri­ence re­peat­ed seizures. 

In the study, the drug didn’t work. Track­ing ob­serv­able as well as “ab­sence seizures,” a tem­po­rary loss of at­ten­tion of­ten marked by a dis­tant stare, re­searchers record­ed an unim­pres­sive 13.4% re­sponse rate in over­all seizure fre­quen­cy (p=0.41) among 25 pa­tients in the drug arm and 11 in the place­bo group. That was the pri­ma­ry end­point.

How­ev­er…

If you take out the more se­vere ob­serv­able seizure rate and con­cen­trate on a sec­ondary end­point for the so-called ab­sence seizures, the drug sparked a 47% drop in their small group. And that was sta­tis­ti­cal­ly sig­nif­i­cant.

In their state­ment to­day, the biotech says that they cob­bled to­geth­er a va­ri­ety of da­ta that was avail­able, high­light­ing a sig­nif­i­cant drop in “the mean an­nu­al­ized rate of ma­jor clin­i­cal events.”

The FDA un­der Scott Got­tlieb has re­peat­ed­ly sig­naled their will­ing­ness to ex­am­ine new ap­proach­es to short­en­ing the time­line on drug de­vel­op­ment. And Ul­tragenyx says it will be ready to roll if they get a green light.

Shares of Ul­tragenyx, which has en­joyed a cou­ple of key ap­provals, are up 3% in pre-mar­ket trad­ing.

“We ap­pre­ci­ate FDA’s re­view of mul­ti­ple da­ta sub­mis­sions and col­lab­o­ra­tion with us to de­vel­op a path for an ear­ly fil­ing, and it is our com­mit­ment to get this im­por­tant po­ten­tial treat­ment to pa­tients with this se­ri­ous dis­ease as quick­ly as pos­si­ble,” said Emil D. Kakkis, the CEO of Ul­tragenyx. “We will meet with the FDA to dis­cuss the de­tails of the NDA sub­mis­sion and, if ap­proved, ap­pro­pri­ate post-ap­proval com­mit­ments to fur­ther eval­u­ate long-term out­comes of UX007 in pa­tients with LC-FAOD.” 

Im­age: YouTube

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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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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