AXS-05 (dextromethorphan / bupropion Hloov Tus Tso Cai Sawv Cev) Nkag mus rau Ntu 3 Kev Tshuaj Ntsuam Xyuas!

Axsome Tshuaj yog lub tuam txhab biopharmaceutical nplooj siab rau kev tsim kho tshiab ntawm kev kho mob los kho cov kab mob hauv nruab nrab (CNS). Tsis ntev los no, lub tuam txhab tau tshaj tawm txog ACCORD (Kev Ntsuam Xyuas Kev Tshawb Nrhiav Kev Tshawb Fawb hauv Kev Tshawb Fawb Txog Alzheimer Tus Kab Mob) kev kawm, kev tshawb xyuas qhov tseeb, ob chav dig muag, qhov chaw tshuaj xyuas cov theem 3 uas yuav soj ntsuam AXS-05 (dextromethorphan / amphetamine). Txoj kev ua tau zoo thiab kev nyab xeeb ntawm ketones raug hloov kho-kho nyob rau hauv kev kho mob Alzheimer' s mob kev ntxhov siab (AD) kev ntxhov siab.

Tam sim no, tsis muaj tshuaj pom zoo kom kho AD agitation. AXS-05 yog qhov ncauj tawm tshiab NMDA receptor antagonist nrog cov haujlwm ntau. Cov ntaub ntawv los ntawm Ntu II / III ADVANCE-1 txoj kev tshawb fawb qhia tau tias piv nrog cov placebo, AXS-05 tuaj yeem ua kom sai, muaj txiaj ntsig zoo thiab txhim kho kev ntxhov siab ntawm AD cov neeg mob.

Lub Rau Hli Ntuj xyoo no, Asmeskas FDA tau tso cai rau AXS-05 Chaw Tsim Tshuaj Tshuaj Yeeb (BTD) rau kev kho qhov mob AD kev ntxhov siab. Nov kuj tseem yog zaum ob uas AXS-05 tau txais BTD los ntawm Asmeskas FDA. Yav dhau los, FDA tau tso cai AXS-05 BTD rau kev kho mob ntawm kev cuam tshuam loj (MDD) thiab Kev Tawm Tsam Kev Ntsej Muag (FTD) rau kev kho mob ntawm kev nyuaj siab (TRD) thiab AD kev ntxhov siab.

Herriot Tabuteau, MD, CEO ntawm Axsome tau hais tias:" Kev tshaj tawm ntawm Theem 3 ACCORD kev sim rau Alzheimer kev ntxhov siab tseem txuas ntxiv kho kev txhim kho ntawm AXS-05 los kho tus kab mob hnyav no. AXS-05 muaj cov yam ntxwv zoo ntawm cov tshuaj pharmacological. Lub peev xwm hauv qhov ntsuas no yog kev txhawb nqa los ntawm cov txiaj ntsig zoo ntawm peb qhov kev sim ua tiav ADVANCE sim. Alzheimer kev ntxhov siab yog ib qho muaj thiab debilitating tus kab mob, thiab kev tso kawm ntxov hauv cov tsev laus tau ua kom muaj kev puas tsuaj sai ua rau muaj kev pheej hmoo tuag taus. Tam sim no tsis muaj tshuaj pom zoo rau kev kho mob Alzheimer qhov kev ntxhov siab. Yog tias ua tiav, AXS-05 muaj qhov tuaj yeem daws qhov kev xav tau tiag tiag no thiab txhim kho cov neeg mob thiab lawv lub neej."

Alzheimer' s kab mob (AD) yog cov kev paub dementia ntau tshaj plaws, uas yog tus yam ntxwv poob qis thiab kev coj tus cwj pwm thiab lub siab ntsws suav nrog kev nyob tsis tswm. Kev ua kom paub tseeb tuaj yeem pom nyob hauv 70% ntawm AD cov neeg mob, uas cuam tshuam txog kev ua kom tsis muaj peev xwm hauv lub peev xwm, kev tso ntxov hauv cov tsev laus, thiab nce ntawm cov neeg tuag.

AXS-05 yog qhov tshiab, lub qhov ncauj, kev txhawb nqa NMDA receptor antagonist nrog cov haujlwm multimodal thiab tam sim no nyob hauv chaw kho mob tau kho rau kev kho mob kev nyuaj siab thiab lwm yam kab mob hauv lub paj hlwb (CNS). AXS-05 yog li ntawm cov tswv uas muaj tswv thiab ntau npaum ntawm dextromethorphan thiab bupropion, thiab siv Axsome' s s metabolic inhibition technology.

Qhov dextromethorphan tiv thaiv ntawm AXS-05 yog qhov sib tw tsis yog N-methyl-D-aspartate (NMDA) receptor antagonist, tseem hu ua glutamate receptor modulator, uas yog ib qho kev ua haujlwm tshiab, uas txhais tau tias nws qhov kev ua yog txawv ntawm cov tshuaj kho mob ntxhov siab feem ntau muaj tam sim no. Qhov dextromethorphan tiv thaiv ntawm AXS-05 kuj yog sigma-1 receptor agonist, nicotinic acetylcholine receptor antagonist, serotonin thiab norepinephrine transporter inhibitor. Lub bupropion tivthaiv ntawm AXS-05 tuaj yeem txhim kho txoj hauv kev muaj peev xwm ntawm dextromethorphan. Nws yog norepinephrine thiab dopamine reuptake inhibitor thiab tus nicotinic acetylcholine receptor antagonist. AXS-05 muaj ntau dua 40 daim ntawv xaj US thiab thoob ntiaj teb nrog lub sijhawm tiv thaiv kom txog thaum 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 txiav luam yeeb. Ib qho ntxiv, AXS-05 qhia txog kev pib nrawm hauv Alzheimer' s kev kub ntxhov thiab kev ntxhov siab piv nrog tshuaj zoo thiab tshuaj placebo.

FDA tau tso cai rau AXS-05 tsim kev tshuaj tiv thaiv kev tsim tawm (BTD) rau kev kho mob Alzheimer' s kab mob, raws li cov ntaub ntawv los ntawm Kev Tshawb Fawb II / III ADVANCE-1. Qhov no yog randomized, ob-dig muag, tswj, ntau lub chaw, Asmeskas kev sim tsim los ntsuas qhov ua tau zoo thiab kev nyab xeeb ntawm AXS-05 hauv kev kho ntawm kev ntxhov siab AD Hauv txoj kev tshawb no, cov neeg mob 366 tau txais randomized kom tau txais AXS-05 (koob tshuaj nce mus rau 45mg / 105mg, 2 zaug hauv ib hnub), bupropion (koob nce mus rau 105mg, 2 zaug hauv ib hnub), thiab placebo rau kev kho mob txuas ntxiv rau 5 lub lis piam. Qhov ntsuas kev ua tau zoo yog Cohen-Mansfield Agitation Behavior Inventory (CMAI, Korotkoff Scale rau luv luv). CMAI yog 29 qhov khoom ntsuas cov neeg zov menyuam tau siv los ntsuas qhov ntau zaus ntawm kev ua kom muaj kev ntxhov siab nyob hauv cov neeg mob uas dementia, suav nrog kev ua lub cev muaj zog ntau dhau (xws li ua rau tsis pom), hais lus phem (xws li qw thiab qw), thiab kev ua phem rau lub cev (xws li thawb, 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 qhia tau hais tias nyob rau lub lim tiam 5, piv nrog cov placebo pawg, tag nrho cov qhab nia ntawm CMAI hauv pawg AXS-05 raug txo tawm ntawm cov lus: cov pab pawg AXS-05 tsawg dua li ntawm 15.4 cov ntsiab lus los ntawm lub hauv paus, thiab cov placebo pab pawg poob qis. los ntawm qhov nruab nrab ntawm 11.5 cov ntsiab lus (p=0.010). Cov txiaj ntsig no sawv cev tias feem pua ​​nruab nrab ntawm pawg AXS-05 poob qis los ntawm lub hauv paus mus rau 48%, thaum feem pua ​​nruab nrab ntawm cov placebo pawg txo mus rau 38%. AXS-05 kuj tseem zoo dua rau bupropion nyob rau hauv tag nrho cov qhab nia ntawm CMAI (p< 0.001),="" paub="" meej="" tias="" cov="" nyiaj="" pab="" dextromethorphan="" hauv="" cov="">

AXS-05 tuaj yeem txhim kho cov tsos mob ntxhov siab sai. Los ntawm lub lim tiam thib ob, kev txhim kho ntawm AXS-05 rau tag nrho cov qhab nia ntawm CMAI tau suav zoo dua ntawm cov placebo, thiab tau mus txog qhov tseem ceeb ntawm kev tshawb pom tsuas yog li ib lub lim tiam tom qab txhaj tag nrho ntawm AXS-05, uas yog, lub lim tiam thib peb (p=0.007).

Muab piv nrog cov pab pawg placebo, qhov feem pua ​​ntawm cov neeg mob hauv pawg AXS-05 uas ua tiav cov lus teb hauv chaw kuaj mob hauv CMAI (73% vs 57%, p=0.005) tau nce ntawm cov lus, thiab cov chaw soj ntsuam tau txhais tau tias nce ntawm 30 % lossis ntau dua los ntawm theem pib theem siab. Cov txiaj ntsig tau zoo ib yam nrog rau txhua qhov kev ntsuas kev hloov pauv uas ntsuas los ntawm cov kws kho mob siv hloov kho Alzheimer' s Kev Sib Koom Tes Kawm-Kev Hloov Txawv Tag Nrho Cov Kev Ntsuam Xyuas Txawv Dua (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 mob tshwm sim feem ntau hauv pawg AXS-05 yog kev tsaug zog (8.2% hauv pawg AXS-05, 4.1% hauv pawg bupropion, thiab 3.2% hauv pawg placebo), kiv taub hau (6.3%, 10.2%, thiab 3.2% , ntsig txog) Thiab raws plab (4.4%, 6.1%, 4.4%, feem). Hauv AXS-05, bupropion, thiab pawg placebo, tus nqi tsis txiav vim yog cov xwm txheej 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, piv nrog 8.2% thiab 5.7% ntawm bupropion thiab placebo-kho cov neeg mob, 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. Mini Kev Ntsuas Kev Nkag Siab Lub Xeev (MMSE) yog ib txoj kev siv dav dav thoob plaws hauv kev paub ntsuas kev ntsuas. Tsis muaj pov thawj qhia tias cov neeg mob tau txais kev kho mob AXS-05 muaj kev txawj ntse poob qis. Kev kho AXS-05 tsis muaj dab tsi los ua kom loog.