Scynex­is finds it­self in the spot­light with a weapon that may fight a su­per­bug that’s scar­ing the world to death

When Mar­co Tagli­et­ti flew from Am­s­ter­dam to Mi­lan ear­li­er this week, a neigh­bor­ing pas­sen­ger hap­pened to ask what he did for a liv­ing. Up­on learn­ing he was an in­fec­tious dis­ease spe­cial­ist, the pas­sen­ger in­quired whether he had come across the re­cent re­port about this “dif­fi­cult-to-treat new fun­gus.” Up­on dis­em­bark­ing, Tagli­et­ti slid in­to his Uber, when his dri­ver pro­fessed an in­ter­est in his pro­fes­sion. The physi­cian’s an­swer pro­duced a now-fa­mil­iar re­sponse: Have you heard about Can­di­da au­ris?

Mar­co Tagli­et­ti

Such is the state of af­fairs. A com­pre­hen­sive re­port by the New York Times last Sat­ur­day put the spot­light on a stub­born, dif­fi­cult-to-di­ag­nose and treat fun­gal in­fec­tion: Can­di­da au­ris or C. au­ris. The large­ly drug-re­sis­tant mi­crobe, which thrives in peo­ple with com­pro­mised im­mune sys­tems, has emerged mys­te­ri­ous­ly across the globe, pop­ping up in Venezuela, Britain, the Unit­ed States and hav­ing tak­en root in In­dia, Pak­istan and South Africa.

Tagli­et­ti, who has helped bring 35 drugs to mar­ket with stints at For­est Labs, Stiefel Labs and Scher­ing-Plough, runs a small biotech out of Jer­sey City, New Jer­sey called Scynex­is $SCYX — os­ten­si­bly the on­ly US drug de­vel­op­er with an an­ti­fun­gal in late-stage clin­i­cal de­vel­op­ment for the oft’ dead­ly pathogen.

“The CDC has been ac­tu­al­ly been talk­ing about it for the last cou­ple of years, mak­ing dire pre­dic­tions…but ap­par­ent­ly no-one was lis­ten­ing,” Tagli­et­ti said in an in­ter­view with End­points News.

More than 1 in 3 pa­tients with in­va­sive C. au­ris in­fec­tion (for in­stance, an in­fec­tion that af­fects the blood, heart, or brain) die, ac­cord­ing to the CDC, which has deemed the pathogen a “se­ri­ous glob­al health threat.” As of Feb­ru­ary 28, the US agency has record­ed 587 con­firmed cas­es and 30 prob­a­ble cas­es this year.

“C. au­ris at­tach­es from per­son to per­son, to things, to clothes, to the walls. This is why the CDC is so con­cerned about this pathogen, its very sticky, very per­sis­tent and tends to spread,” Tagli­et­ti said, not­ing that the pub­lish­ing of the NYT sto­ry in­spired a se­ries of re­ports glob­al­ly that helped the fun­gus has per­me­at­ed the cul­tur­al zeit­geist.

“From what we know, we are the on­ly com­pa­ny as­sess­ing an in­ves­ti­ga­tion­al treat­ment in C. au­ris. I’m sure now, many oth­ers will fol­low.”

It has been decades since a fresh fam­i­ly of an­ti­fun­gals has come on to the mar­ket — at the mo­ment there are three class­es of an­ti­fun­gals in clin­i­cal use, in­clud­ing azoles and echinocan­dins.

The most pop­u­lar an­ti­fun­gals in use to­day were in­tro­duced in the 1980s and this class is in­creas­ing­ly los­ing its po­ten­cy, as fun­gal pathogens be­come more re­sis­tant. Scynex­is’s lead ex­per­i­men­tal drug — ibrex­a­fungerp — be­longs to a new class of an­ti­fun­gals called glu­can syn­thase in­hibitors, and has shown to be ef­fec­tive against a broad range of fun­gal in­fec­tions, in­clud­ing re­sis­tant strains, Tagli­et­ti said.

Last Oc­to­ber, the com­pa­ny ini­ti­at­ed a late-stage open-la­bel study called CARES in C. au­ris pa­tients. In a pre­sen­ta­tion on Fri­day, Scynex­is will present da­ta at a med­ical con­fer­ence on two pa­tients who were suc­cess­ful­ly treat­ed with the oral ibrex­a­fungerp from the on­go­ing study, which has en­rolled sev­er­al pa­tients so far.

The pas­sage of the lim­it­ed pop­u­la­tion path­way for an­tibac­te­r­i­al and an­ti­fun­gal drugs (LPAD) — es­tab­lished by the 21st Cen­tu­ry Cures Act — al­lows the FDA to ap­prove cer­tain an­ti-in­fec­tive prod­ucts on the ba­sis of lim­it­ed clin­i­cal da­ta. Scynex­is is work­ing with the FDA to sort out how much ibrex­a­fungerp da­ta will make the cut for C. au­ris, Tagli­et­ti said.

The drug is al­so be­ing test­ed for oth­er in­fec­tions. It is in a Phase III study for vagi­nal yeast in­fec­tions. Topline da­ta are ex­pect­ed in the first half of 2020, and if pos­i­tive, the com­pa­ny ex­pects to file a mar­ket­ing ap­pli­ca­tion in the lat­ter half of the year.

One of the biggest chal­lenges fac­ing the field of an­ti­fun­gal drug de­vel­op­ment is the lack of in­cen­tives, such as those af­ford­ed to com­pa­nies in the an­tibac­te­r­i­al and an­tivi­ral space, Tagli­et­ti said.

When the com­pa­ny ap­proached BAR­DA for fund­ing, they were told an­ti­fun­gals were not a pri­or­i­ty in Wash­ing­ton, he said. “I hope this aware­ness will now reach Wash­ing­ton.”

As su­per­bugs flour­ish, the in­dus­try play­ers con­tribut­ing to the ar­se­nal of an­timi­cro­bials are dwin­dling. Com­pa­nies in the an­tibi­ot­ic space have their own set of trou­bles.

Drug­mak­ers are en­ticed by green­er pas­tures, com­pared to the long ar­du­ous path to an­tibi­ot­ic ap­proval that of­fers lit­tle fi­nan­cial gain as treat­ments must be priced cheap­ly, and of­ten lose po­ten­cy over time as bac­te­ria grow re­sis­tant. Be­yond the in­cen­tives al­ready in place to push drug­mak­ers to de­vel­op an­tibi­otics, there have been calls to bring on “pull in­cen­tives,” or pol­i­cy mea­sures to in­crease the val­ue of a mar­ket­ed an­tibi­ot­ic by re­ward­ing drug­mak­ers on­ly af­ter their an­tibi­ot­ic is ap­proved by the FDA.

Tagli­et­ti does not see an­ti­fun­gals fac­ing a sim­i­lar hur­dle. “There is a (big­ger) need for an­ti­fun­gals, there­fore they will not go the same way an­tibac­te­r­i­al sales have gone. The last an­ti­fun­gal ap­proved in 2015 is mak­ing $150 mil­lion in its third year of sales…more than the last 4 or 5 an­tibac­te­ri­als com­bined.”


Im­age: Can­di­da Au­ris. Shut­ter­stock

Brian Kaspar. AveXis via Twitter

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Martin Shkreli [via Getty]

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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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