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.”

Hal Barron, GSK

Break­ing the death spi­ral: Hal Bar­ron talks about trans­form­ing the mori­bund R&D cul­ture at GSK in a crit­i­cal year for the late-stage pipeline

Just ahead of GlaxoSmithKline’s Q2 update on Wednesday, science chief Hal Barron is making the rounds to talk up the pharma giant’s late-stage strategy as the top execs continue to woo back a deeply skeptical investor group while pushing through a whole new R&D culture.

And that’s not easy, Barron is quick to note. He told the Financial Times:

I think that culture, to some extent, is as hard, in fact even harder, than doing the science.

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Aca­dia is mak­ing the best of it, but their lat­est PhI­II Nu­plazid study is a bust

Acadia’s late-stage program to widen the commercial prospects for Nuplazid has hit a wall. The biotech reported that their Phase III ENHANCE trial flat failed. And while they $ACAD did their best to cherry pick positive data wherever they can be found, this is a clear setback for the biotech.

With close to 400 patients enrolled, researchers said the drug flunked the primary endpoint as an adjunctive therapy for patients with an inadequate response to antipsychotic therapy. The p-value was an ugly 0.0940 on the Positive and Negative Syndrome Scale, which the company called out as a positive trend.

Their shares slid 12% on the news, good for a $426 million hit on a $3.7 billion market cap at close.

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Some Big Phar­mas stepped up their game on da­ta trans­paren­cy — but which flunked the test?

The nonprofit Bioethics International has come out with their latest scorecard on data transparency among the big biopharmas in the industry — flagging a few standouts while spotlighting some laggards who are continuing to underperform.

Now in its third year, the nonprofit created a new set of standards with Yale School of Medicine and Stanford Law School to evaluate the track record on trial registration, results reporting, publication and data-sharing practice.

Busy Gilead crew throws strug­gling biotech a life­line, with some cash up­front and hun­dreds of mil­lions in biobucks for HIV deal

Durect $DRRX got a badly needed shot in the arm Monday morning as Gilead’s busy BD team lined up access to its extended-release platform tech for HIV and hepatitis B.

Gilead, a leader in the HIV sector, is paying a modest $25 million in cash for the right to jump on the platform at Durect, which has been using its technology to come up with an extended-release version of bupivacaine. The FDA rejected that in 2014, but Durect has been working on a comeback.

In­tec blitzed by PhI­II flop as lead pro­gram fails to beat Mer­ck­'s stan­dard com­bo for Parkin­son’s

Intec Pharma’s $NTEC lead drug slammed into a brick wall Monday morning. The small-cap Israeli biotech reported that its lead program — coming off a platform designed to produce a safer, more effective oral drug for Parkinson’s — failed the Phase III at the primary endpoint.

Researchers at Intec, which has already seen its share price collapse over the past few months, says that its Accordion Pill-Carbidopa/Levodopa failed to prove superior to Sinemet in reducing daily ‘off’ time. 

Cel­gene racks up third Ote­zla ap­proval, heat­ing up talks about who Bris­tol-My­ers will sell to

Whoever is taking Otezla off Bristol-Myers Squibb’s hands will have one more revenue stream to boast.

The drug — a rising star in Celgene’s pipeline that generated global sales of $1.6 billion last year — is now OK’d to treat oral ulcers associated with Behçet’s disease, a common symptom for a rare inflammatory disorder. This marks the third FDA approval for the PDE4 inhibitor since 2014, when it was greenlighted for plaque psoriasis and psoriatic arthritis.

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Francesco De Rubertis

Medicxi is rolling out its biggest fund ever to back Eu­rope's top 'sci­en­tists with strange ideas'

Francesco De Rubertis built Medicxi to be the kind of biotech venture player he would have liked to have known back when he was a full time scientist.

“When I was a scientist 20 years ago I would have loved Medicxi,’ the co-founder tells me. It’s the kind of place run by and for investigators, what the Medicxi partner calls “scientists with strange ideas — a platform for the drug hunter and scientific entrepreneur. That’s what I wanted when I was a scientist.”

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Af­ter a decade, Vi­iV CSO John Pot­tage says it's time to step down — and he's hand­ing the job to long­time col­league Kim Smith

ViiV Healthcare has always been something unique in the global drug industry.

Owned by GlaxoSmithKline and Pfizer — with GSK in the lead as majority owner — it was created 10 years ago in a time of deep turmoil for the field as something independent of the pharma giants, but with access to lots of infrastructural support on demand. While R&D at the mother ship inside GSK was souring, a razor-focused ViiV provided a rare bright spot, challenging Gilead on a lucrative front in delivering new combinations that require fewer therapies with a more easily tolerated regimen.

They kept a massive number of people alive who would otherwise have been facing a death sentence. And they made money.

And throughout, John Pottage has been the chief scientific and chief medical officer.

Until now.

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Vlad Coric (Biohaven)

In an­oth­er dis­ap­point­ment for in­vestors, FDA slaps down Bio­haven’s re­vised ver­sion of an old ALS drug

Biohaven is at risk of making a habit of disappointing its investors.

Late Friday the biotech $BHVN reported that the FDA had rejected its application for riluzole, an old drug that they had made over into a sublingual formulation that dissolves under the tongue. According to Biohaven, the FDA had a problem with the active ingredient used in a bioequivalence study back in 2017, which they got from the Canadian drugmaker Apotex.

Apotex, though, has been a disaster ground. The manufacturer voluntarily yanked the ANDAs on 31 drugs — in late 2017 — after the FDA came across serious manufacturing deficiencies at their plants in India. A few days ago, the FDA made it official.

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