Af­ter pos­i­tive pan­el vote, Sh­iono­gi an­tibi­ot­ic scores US ap­proval

Safe­ty con­cerns linked with Sh­iono­gi’s an­tibi­ot­ic were put to bed by an ex­pert pan­el to the FDA, who large­ly vot­ed to back the drug for com­pli­cat­ed uri­nary tract in­fec­tions (cU­TI) last month. On Fri­day, the US reg­u­la­tor fol­lowed suit, grant­i­ng the treat­ment of­fi­cial ap­proval.

The drug, brand­ed Fetro­ja, will be used in pa­tients whose (cU­TI) is sus­pect­ed to have been caused by Gram-neg­a­tive pathogens, which are in­creas­ing­ly grow­ing re­sis­tant to stan­dard ther­a­pies.

The tsuna­mi of an­tibi­ot­ic re­sis­tance is an acute glob­al threat. In the Unit­ed States, at least 2.8 mil­lion peo­ple get an an­tibi­ot­ic-re­sis­tant in­fec­tion each year, and more than 35,000 peo­ple die, ac­cord­ing to a re­cent re­port by the CDC.

Sh­iono­gi’s mar­ket­ing ap­pli­ca­tion large­ly re­lied on the re­sults of the piv­otal 448 hos­pi­tal­ized pa­tient-APEKS-cU­TI study — which test­ed its an­tibi­ot­ic against the broad spec­trum reg­i­men of imipen­em/cilas­tatin. Da­ta showed that 72.6% (183/252) of pa­tients in the drug arm met the main com­pos­ite goal of mi­cro­bi­o­log­i­cal erad­i­ca­tion and clin­i­cal re­sponse, ver­sus 54.6% (65/119) in the com­para­tor arm. The rate of se­ri­ous side-ef­fects were sim­i­lar in type and rate be­tween the two groups.

But in the open-la­bel CRED­I­BLE-CR study, which in­ves­ti­gat­ed the ef­fi­ca­cy and safe­ty of the Sh­iono­gi an­tibi­ot­ic (which is known chem­i­cal­ly as ce­fide­ro­col) ver­sus best avail­able ther­a­py (BAT) in 150 pa­tients with ev­i­dence of cer­tain Gram-neg­a­tive pathogens in pa­tients with noso­co­mi­al pneu­mo­nia, blood­stream in­fec­tions/sep­sis, or cU­TI — the rate of deaths on the Fetro­ja arm caused some con­cern.

There was a dif­fer­ence in all-cause mor­tal­i­ty in 18 %, 24.8 %, and 33.7 % of ce­fide­ro­col-treat­ed pa­tients and 12.2 %, 18.4 %, and 18.4 % of BAT-treat­ed pa­tients at Day 14, Day 28, and end of study, re­spec­tive­ly. An in­de­pen­dent pan­el mon­i­tor­ing the study found that half of the pa­tient deaths were the re­sult of the pa­tients’ un­der­ly­ing co-mor­bid­i­ty or in­fec­tion com­pli­ca­tions oth­er than the orig­i­nal Gram-neg­a­tive in­fec­tion for which the pa­tient was ran­dom­ized in­to the study.

Some mem­bers of the ex­pert FDA pan­el ex­pressed cau­tion that the la­bel should re­flect the un­cer­tain­ty with CRED­I­BLE-CR da­ta. Over­all, pan­elists vot­ed 14-2 in fa­vor of the drug,  and the two vot­ed against it sug­gest­ed the com­pound should be fur­ther stud­ied.

Fetro­ja — which is de­signed to pen­e­trate the cell wall of Gram-neg­a­tive bac­te­ria sub­vert many of the re­sis­tance mech­a­nisms that bac­te­ria em­ploy against an­tibi­otics — will be made com­mer­cial­ly avail­able in ear­ly 2020, the Japan­ese drug­mak­er said on Thurs­day.

It is no se­cret that the in­dus­try play­ers con­tribut­ing to the ar­se­nal of an­timi­cro­bials are fast dwin­dling. Drug­mak­ers are en­ticed by green­er pas­tures, com­pared to the long, ar­du­ous and ex­pen­sive path to an­tibi­ot­ic ap­proval that of­fers lit­tle fi­nan­cial gain as treat­ments must be priced cheap­ly, and of­ten lose po­ten­cy over time as mi­crobes grow re­sis­tant to them.

The be­lea­guered field of an­tibi­otics is des­per­ate for a win­ner. For one of the biggest threats to glob­al health, the li­on’s share of an­tibi­ot­ic de­vel­op­ment is tak­ing place in a hand­ful of labs of small bio­phar­ma com­pa­nies as a ma­jor­i­ty of their larg­er coun­ter­parts fo­cus on more lu­cra­tive en­deav­ors. In re­cent months, a hand­ful of an­tibi­ot­ic de­vel­op­ers — in­clud­ing Achao­gen and Tetraphase — have seen their val­ue go up in smoke as fee­ble drug sales frus­trate growth. But on av­er­age, most fresh­ly ap­proved an­tibi­otics have been more po­tent ver­sions of ex­ist­ing class­es of an­tibi­otics.

So­cial im­age: Sh­iono­gi, Hi­romit­su Mo­ri­mo­to via flickr

Michel Vounatsos, Biogen CEO (via YouTube)

Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

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All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

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A new chap­ter in the de­cen­tral­ized clin­i­cal tri­al ap­proach

Despite the promised decentralized trial revolution, we haven’t yet moved the needle in a significant way, although we are seeing far bolder commitments to this as we continue to experience the pandemic restrictions for some time to come. The vision of grandeur is one thing, but operationalizing and execution are another and recognising that change, particularly mid-flight on studies, is worthy of thorough evaluation and consideration in order to achieve success. Here we will discuss one of the critical building blocks of a Decentralized and Remote Trial strategy: TeleConsent; more than paper under glass, it is a paradigm change and key digital enabler.

Pfizer CEO Albert Bourla (Drew Angerer/Getty Images)

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CRISPR Ther­a­peu­tics gets a snap­shot of off-the-shelf CAR-T suc­cess in B-cell ma­lig­nan­cies — marred by the death of a pa­tient

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Using their gene editing tech, researchers for CRISPR engineered cells from healthy donors into an attack vehicle aimed at cancer, something that has been achieved with great success using patients’ own cells — the autologous approach. But autologous CAR-T is hampered by the more complex vein-to-vein requirement that delays treatment, and now CRISPR Therapeutics along with other players like Allogene are determined to replace the pioneers with CAR-T 2.0.

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Un­fazed by PhII miss, Roche ush­ers Prothena's Parkin­son's drug in­to late-stage tri­al — a $60M move

Prothena’s prasinezumab may not have met the primary endpoint in Phase II, but its partners at Roche are seeing enough to move it into a late-stage trial for Parkinson’s disease.

The Phase IIb will build on the Phase II PASADENA study, adding a subgroup of early Parkinson’s patients on stable levodopa therapy to the population.

It’s a significant milestone for a $600 million deal that dates back to 2013, as dosing of the first patient — expected next year — will trigger a $60 million milestone payment to Prothena.

RBC's Bri­an Abra­hams holds a mock ad­comm on Bio­gen's iffy ad­u­canum­ab da­ta — and most of these ex­perts don't see a path to an ap­proval

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With its big franchise under assault, Biogen is betting the ranch that its mixed late-stage Alzheimer’s data can squeak past the experts and regulators and get onto the market. And the topic — after a decade of Alzheimer’s R&D disasters in what still represents the El Dorado of drug markets — remains in the center ring of discussions around late-stage pipeline prospects.

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CEO Grace Colón (InCarda)

Look­ing to re­pur­pose an old drug to treat ir­reg­u­lar heart­beats, In­Car­da rais­es $30M in first Se­ries C close

A little less than two years after completing its $42 million Series B round, InCarda has returned to the venture well.

The San Francisco-based biotech announced the first portion of its Series C on Wednesday, pulling in $30 million in new funding. Most of the money will give enough runway for InCarda’s InRhythm program, an inhaled therapeutic aiming to treat sudden episodes of irregular heartbeats, through its Phase II trials and prepare it for Phase III.

Covid-19 roundup: Ab­bott prof­its soar on test­ing kits; As­traZeneca could soon re­sume US vac­cine tri­als

Abbott Laboratories, one of the companies at the forefront of Covid-19 testing, is seeing big windfalls as a result of the pandemic.

The company reported its third-quarter results Wednesday morning, noting that overall profit went up 26.9% over the same period in 2019 as well as 28.2% in the first nine months of 2020 compared to that timeframe last year. Abbott’s Covid-19 tests drove the profits after seeing strong demand and helped the company beat quarterly estimates.

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