FDA Tau Txais AXS-05 (dextromethorphan / bupropion Hloov Tus Tso Cai Sawv Cev) Kev Tshawb Fawb Txog Kev Tsim Yeeb Tshuaj!

Axsome Kev Kho Mob yog lub tuam txhab kev kuaj mob-qib biopharmaceutical tsom rau kev tsim kho tshiab rau kev kho mob rau cov kab mob ntawm cov hlab ntsha hauv nruab nrab (CNS). Tsis ntev los no, lub tuam txhab tshaj tawm tias Asmeskas Chaw Tswj Xyuas Khoom Noj thiab Tshuaj (FDA) tau tso cai AXS-05 (dextromethorphan / bupropion hloov kho tus neeg sawv cev) tshuaj tua kab mob kev tsim nyog (BTD) rau kev kho mob Alzheimer' s kab mob (AD) Agitation. Tam sim no, tsis muaj cov tshuaj pom zoo rau kev kho mob ntawm AD agitation.

Nws tsim nyog teev tias qhov no yog zaum ob AXS-05 tau muab BTD los ntawm Asmeskas FDA. Yav dhau los, FDA tau tso cai rau AXS-05 BTD rau kev kho mob ntawm kev nyuaj siab loj (MDD), ntxiv rau kev ceev ceev (FTD) rau kev kho mob ntawm kev nyuaj siab refractory (TRD) thiab AD kev ntxhov siab.

BTD yog lub chaw tshuaj ntsuam xyuas tshuaj tshiab tsim los ntawm FDA hauv xyoo 2012. Nws lub hom phiaj yuav ua kom muaj kev txhim kho sai thiab tshuaj xyuas cov kev kho mob rau cov mob hnyav lossis tuag taus thiab muaj cov ntawv pov thawj ua ntej tias cov tshuaj tuaj yeem txhim kho cov kev mob ntau npaum li cas piv nrog cov tshuaj uas twb muaj lawm. Cov tshuaj tshiab. Kev tau txais cov tshuaj BTD tuaj yeem coj tau zoo dua los ntawm cov thawj coj hauv FDA thaum tshawb nrhiav thiab txhim kho kom ntseeg tau tias cov neeg mob tau txais cov kev kho mob tshiab nyob rau lub sijhawm luv.

Alzheimer' s kab mob (AD) yog cov kev paub dementia ntau tshaj plaws, uas pom los ntawm qhov tsis muaj peev xwm hauv lub peev xwm thiab kev coj tus cwj pwm thiab lub siab ntsws suav nrog kev nyob tsis tswm. Kev ntxhov siab tuaj yeem pom nyob hauv 70% ntawm AD cov neeg mob, uas cuam tshuam txog kev nrawm nrawm poob qis hauv kev txawj ntse, kev tso ntxov hauv cov tsev laus thiab cov neeg tuag tsawg dua. Cov kev tshawb fawb soj ntsuam tau pom tias AXS-05 tuaj yeem hloov kho sai, muaj ntau, thiab txhim kho kev ntxhov siab ntawm AD cov neeg mob piv rau cov placebo.

AXS-05 yog qhov tshiab, lub qhov ncauj, kev txhawb nqa NMDA receptor antagonist nrog multimodal kev ua haujlwm uas tam sim no nyob rau hauv kev kho mob hauv kev kho mob rau kev kho mob siab ntsws thiab lwm yam kab mob hauv nruab nrab (CNS). AXS-05 yog suav nrog cov qauv tsim thiab ntau npaum ntawm dextromethorphan thiab bupropion, thiab siv Axsome' s s metabolic inhibition technology.

Qhov dextromethorphan tivthaiv ntawm AXS-05 yog qhov sib tw tsis-N-methyl-D-aspartate (NMDA) receptor antagonist, tseem hu ua glutamate receptor modulator, uas yog qhov kev hloov pauv ntawm qhov tshiab txhais tau tias nws qhov kev ua yog txawv ntawm kev nyuaj siab feem ntau cov tshuaj muaj tam sim no. Lub dextromethorphan tivthaiv ntawm AXS-05 kuj yog sigma-1 receptor agonist, nicotinic acetylcholine receptor antagonist, serotonin thiab norepinephrine transporter inhibitor. Lub bupropion tivthaiv ntawm AXS-05 txhim kho txoj kev nyab xeeb ntawm dextromethorphan, norepinephrine thiab dopamine reuptake inhibitor thiab nicotinic acetylcholine receptor antagonist. AXS-05 muaj ntau dua 40 daim ntawv xaj US thiab thoob ntiaj teb, thiab lub sijhawm tiv thaiv yog mus txog 2034.

Tam sim no, AXS-05 tau ua pov thawj nws cov hauj lwm hauv Alzheimer' s kev kub ntxhov, kev ntxhov siab, thiab kev sim haus luam yeeb. Ntxiv rau, AXS-05 qhia txog kev pib nrawm hauv Alzheimer' s kev kub ntxhov thiab kev ntxhov siab piv rau cov tshuaj yeeb tshuaj zoo thiab cov chaw siv tshuaj.

Axsome CEO Herriot Tabuteau, MD, hais tias:" Qhov no BTD yog lub sijhawm tseem ceeb hauv kev tsim AXS-05 los kho AD kev ntxhov siab. AD kev ntxhov siab yog ib qho mob hnyav, dav thiab debilitating, thiab tam sim no tseem tsis tau pom zoo cov phiaj xwm kho mob. Nws tseem yog qhov thib ob BTD tau los ntawm AXS-05, hais txog lub peev xwm ntawm AXS-05 daws cov kev kho mob tsis txaus ntseeg nyob rau ntau qhov nyuaj-kho-mob nruab nrab cov kab mob. Peb cia siab tias yuav koom tes nrog FDA hauv lub hlis tom ntej kom dhau AXS -05 R& D rau kev kho mob ntawm AD kev ntxhov siab."

Qhov BTD no yog raws cov ntaub ntawv los ntawm Ntu II / III ADVANCE-1 kev tshawb fawb. Qhov no yog randomized, ob-dig muag, tswj tau, ntau lub zog, Asmeskas kev sim tau tsim los mus ntsuas qhov ua tau zoo thiab kev nyab xeeb ntawm AXS-05 hauv kev kho ntawm kev ntxhov siab AD. Hauv qhov kev tshawb fawb no, 366 cov neeg mob tau txais kev pheej hmoo kom tau txais AXS-05 (koob tshuaj nce mus rau 45 mg / 105 mg ob zaug ib hnub), bupropion (koob nce mus rau 105 mg ob zaug ib hnub), thiab cov placebo rau 5 lub lis piam. Lub ntsiab curative effect Performance index yog Cohen-Mansfield Agitation Emotional Behavior Scale (CMAI, hu ua Kirsch nplai). CMAI yog 29 qhov khoom ntsuas cov neeg zov menyuam tau siv los ntsuas qhov nquag ntawm kev ntxhov siab ntsig txog tus cwj pwm hauv cov neeg mob dementia, suav nrog kev ua lub cev muaj zog ntau dhau (xws li pawm), hais lus tawm tsam (xws li qw thiab qw), thiab kev tawm tsam lub cev (xws li txhom , thawb thiab ntaus).

Thaum kawg ntawm lub Plaub Hlis xyoo no, Axsome tshaj tawm tias qhov kev sim ADVANCE-1 tau mus txog nws qhov kev pom tseeb. Cov ntaub ntawv tau qhia tias lub limtiam 5, piv nrog cov pab pawg placebo, tag nrho cov qhab nia ntawm CMAI ntawm cov neeg mob hauv pawg AXS-05 tau raug txo qis: ua rau qhov nruab nrab txo 15.4 cov ntsiab lus los ntawm cov hauv paus hauv pawg AXS-05 thiab qhov nruab nrab txo ntawm 11.5 cov ntsiab lus hauv cov tso pawg (p=0.010). Cov txiaj ntsig no sawv cev tias qhov feem pua ​​nruab nrab ntawm pawg AXS-05 poob qis los ntawm theem pib mus rau 48%, thaum feem pua ​​nruab nrab ntawm cov placebo pawg txo mus rau 38%. AXS-05 kuj tau tshaj tawm cov bupropion nyob rau hauv tag nrho cov qhab nia ntawm CMAI (p< 0.001),="" paub="" meej="" tias="" cov="" kev="" koom="" ua="" ke="" ntawm="" dextromethorphan="" tivthaiv="" hauv="" cov="">

AXS-05 tuaj yeem txhim kho cov tsos mob ntawm kev ntxhov siab sai sai. Txij li ob lub lim tiam tom ntej, kev txhim kho ntawm CMAI tag nrho cov qhab nia los ntawm AXS-05 tau zoo dua rau cov placebo, thiab nws mus txog qhov tseem ceeb ntawm lub cev tsuas yog ib lub lis piam tom qab txhaj tag nrho ntawm AXS-05, piv txwv li, lub lim tiam thib peb (p=0.007).

Muab piv nrog cov pab pawg placebo, qhov sib piv ntawm cov neeg mob hauv pawg AXS-05 uas tau txais cov lus teb hauv chaw kuaj mob rau CMAI (73% vs 57%, p=0.005) tau nce tawm ntawm cov lus, thiab cov chaw soj ntsuam tau txhais tau tias yog 30% lossis ntau kev txhim kho los ntawm qib theem pib siab. Cov txiaj ntsig tau zoo sib xws nrog kev ntsuam xyuas tag nrho ntawm kev hloov pauv ntsuas los ntawm cov kws kho mob siv hloov kho Alzheimer' s Kab Mob Kev Kawm Sib Koom Tes-Kev Hloov Kho Kev Nyuaj Siab Zuag Tag Nrho (Impression Scale) (mADCS-CGIC). Piv nrog tshuaj placebo, AXS-05 pom tias muaj kev zoo zuj zus ntxiv hauv kev ntxhov siab (p=0.036).

Hauv qhov kev ntsuas no, AXS-05 tau zam zoo. Cov kev xav tshwm sim ntau tshaj plaws hauv pawg AXS-05 yog kev tsaug zog (8.2% hauv pawg AXS-05, 4.1% hauv pab pawg bupropion, thiab 3.2% hauv pawg placebo) thiab kiv taub hau (6.3%, 10.2%, thiab 3.2% , ntsig txog) Thiab raws plab (feem 4.4%, 6.1%, 4.4%). Hauv AXS-05, bupropion, thiab placebo pawg, tus nqi ntawm kev txiav tawm vim tias qhov tshwm sim tsis zoo yog 1.3%, 2.0%, thiab 1.3%, feem. Ntawm cov neeg mob kho nrog AXS-05, 3.1% ntawm cov neeg mob tau mob nyhav, thaum cov neeg kho nrog bupropion thiab cov placebo yog 8.2% thiab 5.7%, feem. Tsis muaj qhov tshwm sim tsis zoo uas cuam tshuam nrog kev kawm txog tshuaj nyob hauv ib pab pawg kho mob. Muaj 1 tuag nyob hauv pawg placebo, 1 tuag hauv pawg bupropion, thiab tsis tuag hauv pawg AXS-05. Kev Tshawb Xyuas Mini-Mental Lub Xeev (MMSE) yog qhov dav dav siv dav dav hauv kev ntsuas kev ntsuas, thiab tsis muaj cov ntaub ntawv pov thawj tias kev ua haujlwm poob qis hauv cov neeg mob tau txais AXS-05. Kev kho AXS-05 tsis muaj dab tsi los ua kom loog.