Tebchaws Asmeskas FDA pom zoo Brexafemme: kho tus mob vulvovaginal candidiasis (VVC), tsuas yog siv tshuaj ib hnub nkaus xwb!

Scynexis yog lub tuam txhab thev naus laus zis tsom mus rau tsim kho cov kev kho mob tshiab kom kov yeej thiab tiv thaiv kev tiv thaiv kab mob thiab tiv taus tshuaj. Tsis ntev los no, lub tuam txhab tshaj tawm tias Asmeskas Cov Khoom Noj thiab Tshuaj Yeeb Tshuaj (FDA) tau pom zoo siv cov tshuaj tua kab mob sib kis tshiab Brexafemme (ibrexafungerp, 150mg, ntsiav tshuaj), uas yog tshuaj noj qhov ncauj uas tsuas yog yuav tsum tau noj ib hnub los kho qhov paum Poj niam cov neeg mob uas muaj tus mob candidiasis ntawm qhov chaw mos (VVC, tseem hu ua" kis kab mob hauv chaw mos")).

Brexafemme sawv cev rau chav kawm tshiab ntawm cov tshuaj tua kab mob tau pom zoo 20 xyoo dhau los thiab yog lub ntiaj teb' thawj qhov dav-spectrum triterpene antifungal tus sawv cev. Thaum Lub Ob Hlis 11, 2021, Hansen Pharma thiab Scinexis tau kos npe rau daim ntawv tso cai tshwj xeeb rau ibrexafungerp hauv Suav Teb. Raws li kev pom zoo, Hansen Pharmaceuticals yuav yog lub luag haujlwm rau kev txhim kho, kev tswj hwm kev pom zoo thiab kev lag luam ntawm ibrexafungerp hauv Suav Teb Loj. Scynexis yuav tau txais kev them nyiaj ua ntej ntawm 10 lab daus las Asmeskas, thiab yuav tau txais kev txhim kho thiab kev lag luam tseem ceeb kev them nyiaj, nrog rau cov nyiaj muag khoom muag.

VVC yog kab mob uas tuaj yeem cuam tshuam txog peb-plaub feem pua ​​ntawm cov poj niam hauv lawv lub neej, tab sis cov kev kho mob muaj kev txwv, tsuas muaj ib hom khoom (azoles) thiab ib yam khoom ntawm qhov ncauj (fluconazole), thiab tsis muaj qhov tshiab tau pom zoo rau ntau tshaj 20 xyoo khoom.

Brexafemme yog thawj zaug thiab tsuas yog siv tshuaj tsis-azole rau kev kho mob ntawm VVC. Nws tsuas siv sijhawm ib hnub thiab tuaj yeem daws cov kab mob sib kis ntawm cov paum ntawm ntau yam mob hnyav. Brexafemme yuav yog qhov kev xaiv tshuaj zoo tshaj plaws hauv kev kho VVC, tshwj xeeb tshaj yog rau cov neeg mob uas tam sim no tsis txaus siab rau cov tshuaj uas twb muaj lawm. Cov txiaj ntsig los ntawm ob theem 3 kev tshawb fawb soj ntsuam ntawm VANISH txoj haujlwm qhia tias Brexafemme muaj txiaj ntsig, nyab xeeb thiab zam tau zoo hauv kev kho VVC rau ib hnub.

Hais txog kev siv tshuaj, qhov koob tshuaj pom zoo rau cov neeg laus thiab poj niam hluas tom qab cev xeeb tub yog 300 mg (2 ntsiav tshuaj ntawm 150 mg), ob zaug ib hnub, nrog ncua sijhawm li 12 teev, rau tag nrho 1 hnub, thiab tag nrho cov tshuaj kho yog 600 mg (4 ntsiav tshuaj ntawm 150 mg). Brexafemme tuaj yeem noj nrog lossis tsis muaj zaub mov. Ua ntej pib kho, rau cov poj niam uas muaj peev xwm ua me nyuam hauv plab, yuav tsum muaj pov thawj xwm txheej. Brexafemme yog contraindicated rau siv thaum cev xeeb tub, thiab nws kuj tseem txwv tsis pub siv rau cov poj niam uas ua xua rau ibrexafungerp.

ibrexafungerpqauv tshuaj

Vulvovaginal candidiasis (VVC), feem ntau paub tias yog cov kab mob kis tau los ntawm Candida, yog qhov thib ob uas ua rau mob vaginitis. Txawm hais tias cov kab mob no feem ntau tshwm sim los ntawm Candida albicans, cov kab mob fluconazole-resistant Candida, xws li Candida glabrata, tau tshaj tawm ntau thiab ntau dua. VVC tuaj yeem ua rau muaj mob hnyav, suav nrog qhov tsis zoo ntawm qhov chaw mos, tsis txaus siab rau kev sib deev, nyuaj siab, thiab poob peev txheej. Cov tsos mob tshwm sim ntawm VVC suav nrog khaus, mob ntawm qhov chaw mos, ua kom khaus, tso tawm ntawm qhov chaw mos, thiab tso tawm qhov paum txawv txav. Nws tau kwv yees tias 70-75% ntawm cov poj niam thoob ntiaj teb yuav muaj tsawg kawg ib qhov kev tawm tsam VVC hauv lawv lub neej, thiab 40-50% ntawm cov poj niam yuav ntsib ob lossis ntau dua VVC tawm tsam. Kwv yees li ntawm 6-8% ntawm cov neeg mob VVC muaj tus kab mob rov tshwm sim, txhais tias tau ntsib tsawg kawg peb ntu nyob rau 12 lub hlis.

Tam sim no, kev kho VVC suav nrog ntau yam tshuaj pleev azole antifungals (clotrimazole, miconazole, thiab lwm yam) thiab fluconazole. Qhov kawg tam sim no tsuas yog tshuaj tiv thaiv kab mob qhov ncauj pom zoo rau kev kho mob VVC hauv Tebchaws Meskas. Fluconazole tshaj tawm txog 55% kev kho tus nqi kho mob ntawm nws daim ntawv lo, thiab tam sim no tseem suav nrog ceeb toom ntawm qhov ua rau muaj menyuam hauv plab, qhia qhov xav tau kev hloov pauv qhov ncauj tshiab. Qhov ncauj fluconazole lossis tshuaj pleev tsis tuaj yeem ua tau raws li qhov xav tau ntawm cov poj niam cov neeg mob uas muaj VVC me ntsis mus rau qhov hnyav, VVC rov tshwm sim, tiv thaiv VVC tshwm sim los ntawm fluconazole Candida, thiab VVC ntawm hnub nyoog muaj menyuam. Ib qho ntxiv, rau VVC cov neeg mob uas tsis teb lossis tsis kam ua rau kev kho mob fluconazole, tsis muaj lwm txoj hauv kev, thiab tsis muaj FDA pom zoo cov khoom los tiv thaiv VVC rov tshwm sim.

Cov tshuaj muaj tshuaj muaj zog ntawm Brexafemme yogibrexafungerp, uas yog qhov tshiab, tshuaj tua kab mob sib kis tau dav thiab thawj tus sawv cev ntawm cov qauv tshwj xeeb ntawm glucan synthase inhibitors, triterpenoids. ibrexafungerp ua ke ua haujlwm zoo ntawm glucan synthase inhibitors nrog qhov muaj peev xwm hloov pauv ntawm qhov ncauj thiab tso ntshav tawm. Tam sim no, cov tshuaj tau tsim los kho cov kab mob hu ua fungal tshwm sim los ntawm Candida (suav nrog Candida auris, C.auris) thiab Aspergillus. Hauv vitro thiab hauv vivo kev tshawb fawb, cov tshuaj tau qhia pom dav dav ua haujlwm tiv thaiv kab mob tiv thaiv ntau yam tshuaj tiv taus kab mob (suav nrog cov kab mob tiv taus azole thiab echinocandin). Yav dhau los, Asmeskas FDA tau tso cai ibrexafungerp qhov ncauj thiab txhaj tshuaj kho tus mob vulvovaginal candidiasis (VVC), kis tus kab mob candidiasis (IC, suav nrog candidiasis), thiab kis tus kab mob aspergillosis (IA) raws li cov khoom tsim nyog kis kab mob (QIDP) thiab Kev Taug Kev Mus Tau Zoo (FTD) , thiab tau tso cai Orphan Drug Qualification (ODD) rau kev kho IC thiab IA cov cim qhia.

Cov ntaub ntawv ua tau zoo ntawm VANISH qhov haujlwm kho mob

FDA pom zoo Brexafemme raws cov ntaub ntawv los ntawm VANISH Phase 3 qhov chaw kho mob. Txoj haujlwm suav nrog 2 qhov kev xaiv, cov tshuaj placebo-tswj theem 3 kev tshawb fawb, uas yog VANISH 303 (NCT03734991) thiab VANISH 306 (NCT03987620). Ob txoj kev tshawb fawb tau siv tus qauv zoo sib xws los tshuaj xyuas qhov ua tau zoo thiab nyab xeeb ntawm Brexafemme 600mg ib hnub ib koob tshuaj (2 koob, 300mg txhua [2 ntsiav tshuaj 150mg], 12 teev sib nrug) hauv kev kho mob vulvovaginal candidiasis (VVC). Txoj kev tshawb xyuas no suav nrog kho (TOC, hnub 8-14) mus ntsib thiab taug qab (FU, hnub 21-29) mus ntsib. Hloov kho lub hom phiaj-los kho cov pej xeem (MITT) suav nrog cov neeg mob uas muaj tus kab mob Candida zoo ntawm lub hauv paus thiab tau noj tsawg kawg ib koob tshuaj tshuaj.

Thawj qhov kawg yog kho qhov chaw kho mob ntawm TOC mus ntsib hnub 10. Kev kho mob kho mob tau txhais tias yog qhov ua kom ploj ntawm txhua qhov chaw mos thiab cov tsos mob (tag nrho S& S qhab nia yog 0); cov ntsiab lus tseem ceeb thib ob suav nrog kev ua tiav ntawm kev tshem tawm cov kab mob fungal ntawm TOC mus ntsib (kev coj noj coj ua tsis zoo)), kev kho mob tau ua tiav ntawm TOC mus ntsib (S& S tag nrho cov qhab nia yog 0 lossis 1), thiab cov tsos mob ploj tag ntawm FU tuaj ntsib hnub tim 25. Cov Cim thiab Cov tsos mob (S& S) tus qhab nia tau txhais tias yog qhov kawg ntawm cov tsos mob (hlawv, khaus, khaus) qhia los ntawm tus kawm thiab cov cim (o, liab, khawb) tshuaj xyuas los ntawm tus kws tshawb fawb. Txhua lub cim thiab cov tsos mob tuaj yeem faib ua tsis muaj, me me, nruab nrab, thiab hnyav. Cov qhab nia sib xws yog 0 txog 3 cov ntsiab lus, thiab tag nrho cov qhab nia sib xyaw yog 0 txog 18 cov ntsiab lus.

Cov txiaj ntsig los ntawm ob qhov kev tshawb fawb ob qho tib si qhia tias: Sib piv nrog cov placebo, Brexafemme muaj qib siab ntawm kev suav sau zoo raws li thawj qhov kawg thiab cov ntsiab lus tseem ceeb thib ob, thiab nws muaj kev nyab xeeb thiab zam tau zoo.

—— Cov txiaj ntsig ntawm kev ua tau zoo ntawm VANISH-306 txoj kev tshawb fawb: Hnub 10 ntawm TOC mus ntsib, 63.3% ntawm pab pawg kho mob Brexafemme ua tiav kev kho mob kho mob (44.0% hauv pawg placebo, p< 0.01),="" thiab="" 58.5="" %="" ntawm="" cov="" neeg="" mob="" ua="" tiav="" kev="" tshem="" tawm="" cov="" kab="" mob="" fungal="" (29.8%="" hauv="" pawg="" placebo,="">< 0.001),="" thiab="" 72.3%="" ntawm="" cov="" neeg="" mob="" ua="" tiav="" kev="" kho="" mob="" zoo="" (54.8%="" hauv="" pawg="" placebo,="" p="0.01);" ntawm="" 25="" hnub="" fu="" mus="" ntsib,="" 73.9%="" ntawm="" cov="" neeg="" mob="" hauv="" pab="" pawg="" kho="" mob="" brexafemme="" ua="" tiav="" cov="" tsos="" mob="" ploj="" mus="" tag="" (52.4%="" hauv="" pawg="" placebo,="" p="">

—— Cov txiaj ntsig ntawm kev ua tau zoo ntawm VANISH-303 txoj kev tshawb fawb: Ntawm TOC mus ntsib hnub 10, 50.5% ntawm pab pawg kho mob Brexafemme ua tiav kev kho mob (28.6% hauv pawg placebo, p=0.001), thiab 49.5% ntawm cov neeg mob ua tiav kev tshem tawm cov kab mob fungal (Pab pawg placebo yog 19.4%, p< 0.001),="" thiab="" 64.4%ntawm="" cov="" neeg="" mob="" ua="" tiav="" kev="" kho="" mob="" zoo="" (pawg="" placebo="" yog="" 36.7%,="">< 0.001);="" ntawm="" 25="" hnub="" fu="" mus="" ntsib,="" 59.6%="" ntawm="" pab="" pawg="" kho="" mob="" brexafemme="" ua="" tiav="" kev="" kho="" mob="" cov="" tsos="" mob="" ploj="" tag="" (44.9%="" hauv="" pawg="" placebo,=""><>