Tebchaws Asmeskas pom zoo cov tshuaj tiv thaiv ntshav siab tshiab baxdrostat, ua rau muaj kev cia siab tshiab rau cov neeg mob ntshav siab refractory.

Thaum Lub Tsib Hlis 18, 2026 Beijing lub sijhawm, US Food and Drug Administration (FDA) tau tso cai "thawj hauv chav kawm" qhov ncauj aldosterone synthase inhibitor baxdrostat (lub npe lag luam: Baxvendy) rau kev lag luam, uas yog siv nrog rau lwm cov tshuaj tiv thaiv kab mob los kho cov neeg laus mob ntshav siab uas tswj ntshav siab tsis zoo.

Qhov no yog lub ntiaj teb thawj zaug pom zoo xaiv aldosterone synthase inhibitor, ua rau muaj kev cuam tshuam loj hauv kev txhim kho cov tshuaj ntshav siab hauv ob xyoo dhau los.

Nyob rau hauv xyoo tas los no, txawm tias muaj ntau yam tshuaj antihypertensive xws li angiotensin -hloov enzyme inhibitors (ACEIs), angiotensin receptor antagonists (ARBs), calcium channel blockers (CCBs), thiab diuretics, txog ib nrab ntawm cov neeg mob tau txais kev kho mob tseem muaj ntshav siab uas tsis tuaj yeem ncav cuag tus qauv. Ntawm lawv, kev tswj tsis tau cov ntshav siab muaj txog li 63%, thiab cov ntshav siab refractory muaj txog li 15%. Nyob rau hauv tag nrho, ze li ntawm 200 lab tus neeg mob sai sai xav tau kev kho mob tshiab.

Cov txheej txheem tshiab: Inhibiting aldosterone synthesis los ntawm qhov chaw

Aldosterone yog ib yam tshuaj uas tso tawm los ntawm adrenal cortex uas ua rau kom ntshav siab los ntawm kev txhawb nqa rov qab nqus ntawm sodium thiab dej los ntawm lub raum. Kev tshawb fawb qhia tau hais tias kwv yees li 25% ntawm cov ntshav siab yog tshwm sim los ntawm qhov tsis sib xws hauv qib aldosterone. Tsis zoo li cov tshuaj uas twb muaj lawm uas feem ntau thaiv cov renin -angiotensin system los yog ncaj qha dilate cov hlab ntsha, baxdrostat txo aldosterone ntau lawm los ntawm qhov chaw los ntawm kev xaiv inhibiting aldosterone synthase (encoded los ntawm CYP11B2 noob).

Nws yog tsim nyog sau cia tias qhov teeb meem loj tshaj plaws hauv kev tsim cov tshuaj no yog nyob rau hauv kev xaiv tswj - CYP11B2 gene encoding aldosterone synthase muaj homology siab ntawm 93% nrog CYP11B1 gene encoding cortisol synthase. Yog tias qhov kev xaiv tsis zoo, tus neeg mob cov qib cortisol tseem yuav cuam tshuam. Baxdrostat tau ua tiav txoj hauv kev no los ntawm kev txo qis aldosterone ntau ntau yam tsis muaj kev cuam tshuam rau cortisol synthesis, yog li zam kev sib deev hormone cuam tshuam txog kev phiv tshuaj feem ntau cuam tshuam nrog cov tshuaj mineralocorticoid receptor antagonists (MRA) xws li spironolactone (xws li txiv neej lub mis loj hlob, kev coj khaub ncaws, thiab lwm yam).

Cov ntaub ntawv kho mob: Qhov tseem ceeb thiab tsis tu ncua ntawm cov ntshav siab

FDA qhov kev pom zoo yog raws li cov txiaj ntsig zoo ntawm Phase III BaxHTN kev sim. Txoj kev tshawb no yog ntau qhov chaw, randomized, ob npaug - dig muag, placebo- tswj kev sim uas tau tso npe rau 796 tus neeg mob uas tau txais yam tsawg kawg ob hom tshuaj tiv thaiv ntshav siab (suav nrog ib qho tshuaj diuretic) tab sis tsis tswj ntshav siab. Cov txiaj ntsig tau pom tias tom qab 12 lub lis piam ntawm kev kho mob, qhov nruab nrab zaum systolic ntshav siab poob los ntawm 14.5 mmHg hauv pawg baxdrostat 1mg, 15.7 mmHg hauv pawg 2mg, thiab tsuas yog 5.8 mmHg hauv pawg placebo; Tom qab kev kho cov placebo, ob pawg koob tshuaj pom tau tias qhov txo qis ntawm 8.7 mmHg thiab 9.8 mmHg, ntsig txog (P<0.001). More importantly, 39% to 40% of patients in the baxdrostat treatment group achieved systolic blood pressure below 130 mmHg, while the placebo group only achieved 18.7% - the compliance rate was about twice that of the placebo group. The above therapeutic effects were highly consistent in the two subgroups of uncontrolled hypertension and refractory hypertension, and the antihypertensive effect was sustained during the 24 week follow-up period.

Tsis tas li ntawd, lwm qhov kev sim Phase III Bax24 ntxiv tau lees paub qhov txo qis ntawm baxdrostat ntawm 24-teev dynamic ntshav siab hauv cov neeg mob uas muaj ntshav siab refractory. Cov pab pawg koob tshuaj 2mg tau pom qhov txo qis ntawm 16.9 mmHg hauv 24-teev cov ntshav siab systolic thiab kev txhim kho tseem ceeb hauv cov ntshav siab systolic thaum hmo ntuj.

Cov yam ntxwv kev nyab xeeb: Hyperkalemia yuav tsum tau tsom xyuas

Hais txog kev nyab xeeb, kev kho mob ntau tshaj plaws - cuam tshuam txog qhov tshwm sim tsis zoo yog hyperkalemia (cov poov tshuaj ntau dua lossis sib npaug li 5.5 mmol / L). Cov ntsiab lus kev soj ntsuam qhia tau hais tias qhov tshwm sim ntawm hyperkalemia hauv pawg baxdrostat yog kwv yees li 2.87 npaug ntau dua li hauv pawg placebo (RR: 2.87; 95% CI: 1.61-5.11), tab sis feem ntau ntawm lawv yog me me mus rau nruab nrab thiab tswj tau. Lwm cov xwm txheej tsis zoo piv rau cov placebo muaj xws li hyponatremia, hypotension, kiv taub hau, thiab nqaij leeg. FDA pom zoo kom saib xyuas cov neeg mob cov tshuaj poov tshuaj thiab sodium ntau npaum li cas ua ntej thiab thaum siv tshuaj, nrog kev pom zoo noj txhua hnub ntawm 2mg. Rau cov neeg mob uas muaj kev pheej hmoo siab ntawm hyperkalemia lossis hyponatremia, koob tshuaj 1mg raug pom zoo.

Clinical daim ntawv thov tus nqi thiab qhov chaw kho mob

Kev pom zoo ntawm baxdrostat sau qhov sib txawv hauv cov txheej txheem tshiab ntawm kev ua ntawm aldosterone synthase inhibition. Hauv kev xyaum kho mob yav dhau los, aldosterone kho mob ntshav siab feem ntau yog tso siab rau mineralocorticoid receptor antagonists xws li spironolactone thiab eplerenone. Txawm hais tias spironolactone siv tau, nws qhov ntev - siv sijhawm yog txwv los ntawm progesterone nyiam thiab tshuaj tiv thaiv androgen phiv; Iprenone muaj ntau dua selectivity tab sis kuj me ntsis antihypertensive nyhuv. Baxdrostat muab txoj hauv kev kho tshiab los ntawm kev ncaj qha inhibiting aldosterone synthesis es tsis txhob thaiv cov receptors, tshwj xeeb tshaj yog haum rau cov neeg mob uas twb tau siv ntau yam tshuaj (xws li diuretics) tab sis tseem tsis tau raws li cov qauv ntshav siab.

Qhov sib ntxiv ntawm baxdrostat yuav tsum hloov kho thaj chaw kho mob rau cov neeg mob ntshav siab tawv ncauj, uas suav txog li 15% ntawm tag nrho cov neeg mob ntshav siab, nrog rau ntau tus neeg mob ntshav siab uas tsis tau tswj hwm nws cov ntshav siab tau hovering rau ntawm ntug ntawm tus qauv kab tau ntev txawm tias zoo li "tus qauv tshuaj". Dr. Bryan Williams, tus kws tshawb fawb tseem ceeb ntawm BaxHTN thiab tus xibfwb ntawm University College London, tau hais tias, 'Qhov kev hloov tshiab no rau kev txo cov ntshav siab muaj peev xwm hloov pauv kev kho mob los ntawm kev tsom mus rau lub hauv paus ua rau muaj kev kub ntxhov tsis tu ncua. Epidemiological cov ntaub ntawv qhia tau hais tias rau txhua txhua 10 mmHg txo cov ntshav siab systolic, qhov kev pheej hmoo ntawm cov kab mob plawv yog txo los ntawm kwv yees li 20%.'

Clinical application prospects thiab cov teeb meem

Kev pom zoo thiab kev sau npe ntawm baxdrostat los ntawm lub sijhawm thaum lub ntiaj teb kev thov rau kev tiv thaiv kev kub ntxhov thiab kev tswj hwm yog qhov tsis tau muaj dhau los sai. Hauv Suav lag luam ib leeg, tag nrho cov neeg mob uas tsis muaj peev xwm tswj tau thiab cov neeg mob ntshav siab refractory yog ze li 200 lab, suav nrog qhov kev thov kho mob loj heev. Los ntawm kev xav ntawm kev lag luam, lub ntiaj teb kev lag luam loj rau kev kho mob ntawm refractory hypertension yuav tsum tau nce ntxiv ntawm kev loj hlob txhua xyoo ntawm kwv yees li 14.85%. Nyob rau tib lub sijhawm, cov neeg sib tw zoo sib xws lorundrostat (Mineralys Therapeutics) kuj tau xa daim ntawv teev npe, thaum vicadrostat (Boehringer Ingelheim) nyob rau theem III kev kho mob theem, thiab aldosterone synthase inhibitor haiv neeg tau nrawm dua.

Txawm li cas los xij, nws tseem yuav tsum tau paub txog thaj tsam ntawm cov pov thawj tam sim no: cov ntaub ntawv uas twb muaj lawm feem ntau yog nyob ntawm lwm qhov kawg ntawm kev txo cov ntshav siab, thiab tsis muaj cov ntaub ntawv qhia txog qhov loj - cov txiaj ntsig tau sim siv cov hlab plawv thiab cerebrovascular hard endpoints (xws li myocardial infarction, stroke, thiab cardiovascular kev tuag) Lub sij hawm ntev lub taub hau rau lub taub hau kev sib piv pov thawj nrog cov kev siv tshuaj uas twb muaj lawm xws li spironolactone kuj yuav tsum tau sau. Hauv kev siv tiag tiag - ntiaj teb no, seb qhov kev saib xyuas thiab kev tswj hwm lub nra ntawm hyperkalemia puas yuav cuam tshuam rau lub sijhawm ntev - kev ua raws cai tseem yuav tsum tau sim hauv kev xyaum. Tsis tas li ntawd, baxdrostat tseem nyob hauv lub ntiaj teb kev kho mob theem, thiab thaum twg nws tuaj yeem siv los ntawm Suav cov neeg mob tseem nyob ntawm qhov kev nce qib tom ntej ntawm kev sau npe thiab kev txiav txim siab ntsuas hauv Suav teb.

Zuag qhia tag nrho, kev pom zoo ntawm baxdrostat tsis yog tsuas yog ib qho tseem ceeb hauv kev txhim kho cov kav dej ntawm cov tshuaj ntshav siab tom qab xyoo ntawm kev ntsiag to, tab sis kuj muab kev kho mob raws li cov txheej txheem tshiab rau ntau lab tus neeg mob uas tau tawm tsam nrog "ntse ntshav siab" ntev. Nrog rau qhov txuas ntxiv ntawm cov pov thawj kho mob, qhov no thawj zaug hauv cov tshuaj hauv chav kawm yuav tsum tau tuav txoj haujlwm tseem ceeb hauv kev kho mob ntshav siab refractory.