Glass half emp­ty: Achao­gen re­ceives split vote from FDA ex­perts on lead an­tibi­ot­ic, shares plunge

An FDA ad­vi­so­ry com­mit­tee has hand­ed down a split vote — yes for one in­di­ca­tion and no for an­oth­er — on Achao­gen’s lead an­tibi­ot­ic, ruf­fling the high ex­pec­ta­tions it set up go­ing in.

In­vestors weren’t hap­py, send­ing Achao­gen stocks down close to 29% in af­ter-hours trad­ing.

The split de­ci­sion car­ries in­ter­est­ing im­pli­ca­tions for oth­er an­tibi­ot­ic mak­ers. In a first, Achao­gen $AKAO sub­mit­ted an NDA with a re­quest to use the Lim­it­ed Pop­u­la­tion An­tibac­te­r­i­al Drug (LPAD) path­way in re­view­ing the drug, pla­zomicin, for the treat­ment of blood­stream in­fec­tions (BSI) due to Car­bapen­em-re­sis­tant En­ter­obac­te­ri­aceae. That hap­pens to be the in­di­ca­tion that the ad­comm vot­ed down; all 15 of them vot­ed yes when it came to treat­ing pa­tients with com­pli­cat­ed uri­nary tract in­fec­tions (cU­TI).

Pack­aged in­to the 2016 21th Cen­tu­ry Cures Act, the LPAD reg­u­la­to­ry path­way al­lows for ac­cep­tance of greater un­cer­tain­ty or high­er risk in pa­tients with se­ri­ous dis­eases (and an un­met need) pro­vid­ed that sub­stance ev­i­dence of ef­fec­tive­ness is pre­sent­ed.

A large part of what seems to have doomed Achao­gen’s plans for the BSI in­di­ca­tion was a small­er-than-ex­pect­ed sam­ple size that com­pli­cat­ed sta­tis­ti­cal analy­sis. Ear­ly in the meet­ing, an FDA clin­i­cal re­view­er point­ed out that the biotech had to amend pro­to­cols for a Phase III study (ACHN-490-007) be­cause they could on­ly en­roll 37 pa­tients out of the 286 planned. That re­sult­ed in sta­tis­ti­cal lim­i­ta­tions in con­clud­ing that pla­zomicin had su­pe­ri­or ef­fi­ca­cy com­pared to col­istin in the com­para­tor arm, even though nu­mer­i­cal trends point­ed to that con­clu­sion.

The re­view­er went on to sug­gest look­ing at the da­ta through the lens of non­in­fe­ri­or­i­ty, which the da­ta would al­low for, but cau­tioned that such as­sess­ments are com­pli­cat­ed by de­sign fea­tures the FDA agreed to back when Achao­gen was plan­ning a su­pe­ri­or­i­ty tri­al. Among those fea­tures: pri­or or con­comi­tant an­tibac­te­r­i­al ther­a­py, as well as lax­er cri­te­ria for pa­tients re­gard­ing bac­te­ria cul­ture in their bod­ies. That ad­di­tion­al un­cer­tain­ty re­gard­ing base­line sta­tus for pa­tients didn’t help, ei­ther.

Af­ter dis­cussing the sta­tis­ti­cal plan and clar­i­fy­ing how best to bal­ance the LPAD con­sid­er­a­tion with ben­e­fit-risk as­sess­ments, 11 com­mit­tee mem­bers vot­ed against pla­zomicin in BSI, most­ly con­cerned that the study was un­der­pow­ered to sup­port con­clu­sions of ef­fi­ca­cy. The oth­er four dis­agreed, cit­ing the lim­it­ed use and un­met need.

For cU­TI, on the oth­er hand, com­mit­tee mem­bers had no prob­lem unan­i­mous­ly en­dors­ing pla­zomicin based on a study that showed its was non­in­fe­ri­or to meropen­em, even con­sid­er­ing a larg­er mar­gin of 15% (ver­sus a con­ven­tion­al 10%) the FDA sanc­tioned.

Achao­gen CEO Blake Wise had this to say in a short state­ment:

We are en­cour­aged by the Com­mit­tee’s unan­i­mous vote in fa­vor of pla­zomicin for com­pli­cat­ed uri­nary tract in­fec­tions (cU­TI). The dis­cus­sion un­der­scored the re­al-world chal­lenges that health­care providers face every day giv­en lim­it­ed or in­ad­e­quate treat­ment op­tions for cer­tain pathogens. Re­gard­ing blood­stream in­fec­tions, the Lim­it­ed-Pop­u­la­tion An­tibac­te­r­i­al Drug path­way, or LPAD, is a nov­el ap­proach that en­ables the FDA to con­sid­er the ben­e­fits and risks for the sick­est pa­tients who have few or no avail­able treat­ment op­tions, and to ap­prove an­tibi­otics like pla­zomicin that we be­lieve, have the po­ten­tial to ad­dress these lim­it­ed pa­tient pop­u­la­tions.

South San Fran­cis­co-based Achao­gen is one of a hand­ful of biotechs in late-stage de­vel­op­ment with new an­tibi­otics in an era of ris­ing drug re­sis­tance to the main­stays in the field. Whether it will be­come a trail­blaz­er or a cau­tion­ary tale will be­come clear by its PDU­FA date of June 25.

Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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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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Why would Am­gen want to buy Alex­ion? An­a­lysts call hot­ly ru­mored takeover un­like­ly, but seize the mo­ment

A rumor that Amgen is closing in on buyout deal for Alexion has sparked a guessing game on just what kind of M&A strategy Amgen is pursuing and how much Alexion is worth.

Mizuho analyst Salim Syed first lent credence to the report out of the Spanish news outlet Intereconomía, which said Amgen is bidding as much as $200 per share. While the source may be questionable, “the concept of this happening doesn’t sound too crazy to me,” he wrote.

FDA asks why No­var­tis took two months to launch for­mal in­ter­nal probe, af­ter AveX­is flagged da­ta ma­nip­u­la­tion

And the plot thickens. Novartis $NVS officials are reportedly now scrambling to explain to the FDA why it took them two months to open an internal investigation into data discrepancies for their $2.1 million gene-therapy for spinal muscular dystrophy — the world’s most expensive drug.

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Hal Barron. GSK

GSK's Hal Bar­ron her­alds their sec­ond pos­i­tive piv­otal for cru­cial an­ti-BC­MA ther­a­py, point­ing to a push for quick OKs in a crowd­ed field

Hal Barron has his second positive round of Phase III data in hand for his anti-BCMA antibody drug conjugate belantamab mafodotin (GSK2857916). And GSK’s research chief says the data paves the way for their drive in search of an FDA approval for treating multiple myeloma.

It’s hard to overestimate the importance of this drug for GSK, a cornerstone of Barron’s campaign to make a dramatic impact on the oncology market and provide some long-lost excitement for the pharma giant’s pipeline. They’re putting this BCMA program at the front of that charge — looking to lead a host of rivals all aimed at the same target.

We don’t know what the data are yet, but DREAMM-2 falls on the heels of a promising set of data delivered 5 months ago for DREAMM-1. There investigators noted that complete responses among treatment-resistant patients rose to 15% in the extra year’s worth of data to look over, with a median progression-free survival rate of 12 months, up from 7.9 months reported earlier. The median duration of response was 14.3 months.

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UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

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Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll