PhI­II bust forces Ul­tragenyx to scrap drug for rare mus­cle dis­ease

Emil Kakkis, Ul­tragenyx

An­a­lysts had been spec­u­lat­ing that a suc­cess in Ul­tragenyx’s Phase III study of Ace-ER for rare cas­es of GNE my­opa­thy could trig­ger some near-term reg­u­la­to­ry fil­ings. Now, they’re be­ing forced to write it off com­plete­ly as in­ves­ti­ga­tors re­port that the drug failed the pri­ma­ry and sec­ondary end­points, spurring the biotech to write it off com­plete­ly.

The pri­ma­ry goal for the Phase III study of Aceneu­ram­ic Acid Pro­longed Re­lease, which en­rolled more than 80 pa­tients, was a com­pos­ite test for up­per ex­trem­i­ty mus­cles. The sec­on­daries al­so fo­cused on mus­cle strength as well. But af­ter re­port­ing what it terms en­cour­ag­ing mid-stage da­ta, the ther­a­py flunked the piv­otal test.

Shares of Ul­tragenyx slid 10% on the news.

GNEM is a se­vere mus­cle dis­ease caused by an en­zyme de­fi­cien­cy.

No­va­to, CA-based Ul­tragenyx $RARE had tried, and failed to win over Eu­ro­pean reg­u­la­tors for a con­di­tion­al ap­proval af­ter its ex­pert ad­vi­sors con­clud­ed last year that they want­ed to see the Phase III da­ta be­fore they ap­proved the mar­ket­ing. For some an­a­lysts like Leerink’s Joseph Schwartz, the Phase II da­ta left a lot to be de­sired. He not­ed:

In­vestors may re­call that the ear­li­er 48-week Ph.2 study was de­signed to serve as a hy­poth­e­sis-gen­er­at­ing ex­plo­ration study. This Ph.2 study had oth­er is­sues in­clud­ing a small sam­ple size, a lack of pri­ma­ry end­point, and a pre-spec­i­fied un­blind­ing that all con­tributed to the in­vestors’ low­ered sen­ti­ment. Al­though mgmt. ex­pressed op­ti­mism that a Ph.3 study would ad­dress the pre­ced­ing tri­al’s weak­ness­es and demon­strate more ro­bust ef­fi­ca­cy da­ta, we be­lieve that progress on this as­set and the prospects of GNEM was not a pri­or­i­ty amongst in­vestors.

Ul­tragenyx has a num­ber of projects in the clin­ic, and will turn to the oth­er work as it com­pletes last rites for Ace-ER. There’s a BLA be­ing planned for buro­sum­ab, a drug de­vel­oped with Japan’s Ky­owa Hakko Kirin that post­ed pos­i­tive Phase III re­sults in April for X-linked hy­pophos­phatemia (XLH) and Tu­mor-in­duced os­teo­ma­la­cia (TIO). But the biotech has al­so had oth­er re­cent set­backs, in­clud­ing a failed Phase II for UX007 , which was test­ed as a treat­ment for glu­cose trans­porter type-1 de­fi­cien­cy syn­drome—or Glut1 DS—among a small group of pa­tients. The drug on­ly cut the rate of seizures in the drug arm by 13.4% com­pared to the place­bo arm, falling short of sta­tis­ti­cal sig­nif­i­cance.

“We are dis­ap­point­ed by these re­sults, as we had hoped that Ace-ER would of­fer a new op­tion for GNEM pa­tients. We would like to thank the pa­tients, care­givers, and in­ves­ti­ga­tors in­volved in the Ace-ER de­vel­op­ment pro­gram,” said Emil Kakkis, CEO at Ul­tragenyx. “This out­come does not af­fect our over­all strat­e­gy, as the com­pa­ny moves for­ward with mul­ti­ple pre­clin­i­cal and clin­i­cal pro­grams and reg­u­la­to­ry fil­ings.”

Paul Hudson, Getty Images

UP­DAT­ED: Sanofi CEO Hud­son lays out new R&D fo­cus — chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 67,400+ biopharma pros reading Endpoints daily — and it's free.

De­vel­op­ment of the Next Gen­er­a­tion NKG2D CAR T-cell Man­u­fac­tur­ing Process

Celyad’s view on developing and delivering a CAR T-cell therapy with multi-tumor specificity combined with cell manufacturing success
Overview
Transitioning potential therapeutic assets from academia into the commercial environment is an exercise that is largely underappreciated by stakeholders, except for drug developers themselves. The promise of preclinical or early clinical results drives enthusiasm, but the pragmatic delivery of a therapy outside of small, local testing is most often a major challenge for drug developers especially, including among other things, the manufacturing challenges that surround the production of just-in-time and personalized autologous cell therapy products.

Bris­tol-My­ers shows off a low-pro­file AML con­tender it gained from Cel­gene buy­out — and they’re tak­ing it straight to the FDA

Bristol-Myers Squibb reaped an enormous pipeline with its much-criticized $64 billion megadeal to buy Celgene. And it got a few hidden gems in the deal.

One of those gems was brought out for display on Tuesday, with a late-breaker at ASH on CC-486, which is now being prepped for regulatory filings at the FDA and elsewhere.

Celgene top-lined the positive results in a maintenance setting for acute myeloid leukemia a few months ago, but at ASH investigators pulled back the curtains on the all-important data they believe will give them an advantage in the commercial wars to come.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 67,400+ biopharma pros reading Endpoints daily — and it's free.

De­sert­ed by Astel­las and Mer­ck, lit­tle Cor­re­vio still can't win over FDA pan­el con­cerned with its AFib drug's safe­ty

When the FDA spurned Astellas’ pitch for atrial fibrillation drug vernakalant in 2008, regulators made it abundantly clear that it wasn’t the efficacy they had a problem with — two Phase III trials had shown the drug successfully restored 52% of patients’ heartbeat from irregular to normal — but the cardio safety issues for a drug that was to compete with well established, low-risk options. One licensing deal, one clinical hold and several studies later, the chances of approval aren’t looking any better.

New trade deal knocks out long-sought patent pro­tec­tions for drug­mak­ers

House Democrats negotiating with the Trump Administration on a new North American trade deal settled early on four issues: enforcement, labor and environmental standards and drug pricing.

On drug pricing, Politico reports, Trump crumbled within weeks of heightened negotiations.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 67,400+ biopharma pros reading Endpoints daily — and it's free.

With loom­ing su­per­bug cri­sis, Iterum miss­es in a key an­tibi­ot­ic tri­al — and its shares tum­ble

A raft of antibiotic makers have crashed and burned recently despite getting their drugs across the finish line. Iterum Therapeutics hopes that its lead drug sulopenem, which has an outpatient focus in addition to hospitals and a plan to target areas with the highest levels of drug-resistant infections, will avert some of those reimbursement challenges. However, the company has now stumbled in a late-stage study, diminishing its shot at FDA approval it first requires.

UP­DAT­ED: Lit­tle Leo Phar­ma en­ters the prize-fight ring with pos­i­tive PhI­II atopic der­mati­tis da­ta. Now they just have to beat Dupix­ent

A day after new Sanofi CEO Paul Hudson staked his reputation and the future of the pharma giant on making Dupixent a megasuccess story, little Leo Pharma is throwing down the gauntlet on atopic dermatitis.

Three years ago Leo paid AstraZeneca $115 million to buy up rights to use tralokinumab against atopic dermatitis — with $1 billion more on the table in milestones — the Danish company says their drug has swept up positive results for all primary and secondary endpoints in three Phase III trials. Now they plan to start the final push for regulatory approvals so they can challenge the heavyweight champions in this slugfest.

Paul Hudson, Sanofi

Paul Hud­son promis­es a bright new fu­ture at Sanofi, kick­ing loose me-too drugs and fo­cus­ing on land­mark ad­vances. But can he de­liv­er?

Paul Hudson was on a mission Tuesday morning as he stood up to address Sanofi’s new R&D and business strategy.

Still fresh into the job, the new CEO set out to convince his audience — including the legions of nervous staffers inevitably devoting much of their day to listening in — that the pharma giant is shedding the layers of bureaucracy that had held them back from making progress in the past, dropping the duds in the pipeline and reprioritizing a more narrow set of experimental drugs that were promised as first-in-class or best-in-class.  The company, he added, is now positioned to “go after other opportunities” that could offer a transformational approach to treating its core diseases.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 67,400+ biopharma pros reading Endpoints daily — and it's free.

Otello Stampacchia. Omega Funds

Af­ter sev­er­al high pro­file start­up launch­es, om­niv­o­rous Omega Funds clos­es $438M fund to pur­sue more deals

Omega Funds likes to work backwards. It invests with the end game — denoted by the Greek letter in its name — in mind, and it keeps tabs on the number of marketed medical products that culminate from its ventures: 37 in 16 years.

So when founder and managing director Otello Stampacchia declares it’s the most exciting time to be investing in life sciences in a generation, it’s perhaps only natural that Omega has closed its largest fund to date. With $438 million in total commitments for Fund VI, the firm will continue injecting capital into a broad swath of companies across the US and Europe.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 67,400+ biopharma pros reading Endpoints daily — and it's free.