Thawj Qhov Kev Ntsuas Ntshav Qab Zib Ua Ntej Hauv 20 Xyoo - Aldosterone Synthase Inhibitor Baxdrostat Tso Cai Pom Zoo los ntawm FDA rau Kev Lag Luam

Thaum Lub Tsib Hlis 18, 2026, US Food and Drug Administration (FDA) tau tso cai rau AstraZeneca lub ntiaj teb thawj aldosterone synthase inhibitor (ASI), baxdrostat (lub npe lag luam: Baxbendy), rau kev siv ua ke nrog lwm cov tshuaj tiv thaiv kab mob los kho cov neeg laus cov neeg mob ntshav siab uas tswj ntshav siab tsis zoo. Qhov no yog thawj pawg tshuaj tiv thaiv kab mob siab nrog rau cov txheej txheem tshiab ntawm kev ua haujlwm kom nkag mus rau kev kho mob hauv ntau dua 20 xyoo, tom qab beta blockers, RAAS inhibitors, thiab calcium channel blockers.

 

Yav dhau los, thaum Lub Ob Hlis 2026, Baxdrostat daim ntawv thov kev lag luam tau lees paub hauv Suav teb thiab tam sim no tab tom saib xyuas los ntawm National Medical Products Administration (NMPA). Nws xav tias yuav ua kom cov txiaj ntsig zoo rau ntau lab tus neeg mob ntshav siab uas tswj ntshav siab tsis zoo hauv Suav teb.

 

Kev kho mob tsis tau raws li qhov xav tau

 

Kev kub siab yog qhov tseem ceeb hloov pauv tau zoo rau cov kab mob plawv thiab kev tsis taus thoob ntiaj teb. Txawm li cas los xij, txawm tias nyob rau hauv cov qauv pom zoo triple lossis quadruple antihypertensive kev kho mob hauv ntau lub teb chaws cov lus qhia, feem ntau ntawm cov neeg mob tseem muaj ntshav siab uas tsis tuaj yeem ua tau raws li tus qauv.

 

Ib qho kev tshuaj ntsuam meta- suav nrog ntau dua 3.2 lab tus neeg mob ntshav siab tau pom tias qhov tshwm sim ntawm qhov tseeb refractory ntshav siab yog kwv yees li 10.3% (95% CI 7.6% -13.2%) ntawm cov neeg tau txais kev kho mob ntshav siab, thaum qhov tshwm sim ntawm qhov pom tseeb ntawm refractory hypertension yog siab li 14.7%. Hauv cov pej xeem uas muaj kab mob hauv lub raum tsis sib xws, qhov kev faib ua feem ntawm refractory hypertension yog siab li 22.9%. Nws tau kwv yees tias muaj kwv yees li 1.4 billion tus neeg mob ntshav siab thoob ntiaj teb, uas txhais tau tias ntau dua 100 lab tus tib neeg tab tom ntsib kev tswj ntshav siab mus ntev.

 

Yog vim li cas vim li cas refractory hypertension nyuaj rau tswj yog tias aldosterone ntau dhau yog ib qho ntawm cov txheej txheem tseem ceeb uas yog qhov tsis txaus ntseeg. Kev tshawb fawb qhia tau hais tias feem ntau ntawm cov thawj aldosteronism nyob rau hauv cov neeg mob hypertensive tej zaum yuav siab li 5% -10%, thiab ntau yam kev tshawb fawb tsis ntev los no tau pom tias nws qhov tseeb prevalence yuav ntau dua peb zaug; Txawm li cas los xij, tam sim no kev tshuaj ntsuam xyuas tus kab mob no tsawg dua 1%. Qhov nthuav dav "subclinical aldosterone autocrine secretion" muaj nyob rau hauv ntau tus neeg mob uas muaj ntshav siab thawj zaug uas nws cov ntshav siab tswj tau yooj yim.

 

Mechanism of action: Targeting the culprit of aldosterone ntau dhau

 

Baxdrostat yog ib qho tshuaj me me hauv qhov ncauj (ib zaug ib hnub). Los ntawm qhov tseeb inhibiting aldosterone synthetase (CYP11B2), nws thaiv cov synthesis ntawm adrenal aldosterone los ntawm cov hauv paus hniav, yog li txo cov sodium thiab dej tuav hauv lub raum, txo cov ntshav ntim thiab peripheral vascular resistance, thiab ua tiav lub hom phiaj ntawm kev txo cov ntshav siab.

 

Nws cov txiaj ntsig thev naus laus zis tseem ceeb nyob hauv kev xaiv siab: Baxdrostat muaj kev xaiv rau aldosterone synthase (CYP11B2) uas yog ntau dua 100 npaug siab dua li ntawd rau cortisol synthase (CYP11B1), txo qis aldosterone ntau ntau yam tsis muaj kev cuam tshuam rau kev sib xyaw ntawm cortisol ib txwm muaj kev nyab xeeb ntawm adrenal cortisol. thaum ntxov ASI vim cortisol inhibition.

 

Piv nrog rau cov mineralocorticoid receptor antagonists uas twb muaj lawm (MRA, xws li spironolactone thiab eplerenone), cov txheej txheem ntawm kev ua ntawm ASI yog ntau dua: MRA "blocks lub rooj vag" (antagonizes aldosterone receptors), thaum Baxdrostat "kaw tawm dej" (inhibits aldosterone synthesis).

 

Qhov sib txawv tseem ceeb no yuav tsum coj los ntawm kev sib deev hormone cuam tshuam txog kev phiv xws li tsis yog spironolactone ntsig txog txiv neej lub mis kev loj hlob, nrog rau kev tswj tau ntau dua ntawm hyperkalemia piv rau MRA.

 

BaxHTN Phase III Kawm (tshaj tawm hauv NEJM)

 

BaxHTN yog multicenter, randomized, ob npaug - dig muag, placebo- tswj kev sim uas tau tso npe rau 796 cov neeg mob uas tswj ntshav siab tsis zoo raws li 2 (xws li diuretics) lossis ntau dua lossis sib npaug rau 3 cov tshuaj tiv thaiv ntshav siab. Nws tau luam tawm ib txhij nyob rau hauv New England Journal of Medicine thaum Lub Yim Hli 2025. Lub hnub nyoog nruab nrab ntawm cov neeg koom nrog yog 62 xyoo, 39% yog poj niam, thiab 73% koom nrog pab pawg refractory hypertension.

 

Cov txiaj ntsig tseem ceeb tau pom tias Baxdrostat 1 mg pawg muaj 14.5 mmHg txo qis hauv cov ntshav siab zaum systolic piv rau cov hauv paus thiab qhov txo qis ntxiv 8.7 mmHg piv rau cov placebo pawg; Cov pab pawg Baxdrostat 2 mg tau pom tias 15.7 mmHg txo qis hauv cov ntshav siab zaum systolic piv rau cov hauv paus thiab qhov txo qis ntxiv 9.8 mmHg piv rau cov placebo pawg. Cov pab pawg placebo muaj qhov txo qis ntawm tsuas yog 5.8 mmHg.

 

Cov txiaj ntsig thib ob: Kev ua raws li cov ntshav siab systolic<130 mmHg in the 2 mg group was 40%, nearly twice that of the placebo group (18.7%); Both dose groups achieved statistically significant reductions in diastolic blood pressure; The randomized withdrawal period (8 weeks) confirmed the sustained antihypertensive effect: the SBP of the continued medication group further decreased by 3.7 mmHg, while the placebo group rebounded and increased by 1.4 mmHg (p=0.0016)

Bax24 Phase III Kawm (tshaj tawm hauv Lancet, Peb Hlis 2026)

 

Txhawm rau txhim kho qhov ua tau zoo ntawm kev saib xyuas ntshav siab, Bax24 txoj kev tshawb fawb tau siv 24-teev cov ntshav siab dynamic ntshav siab ua thawj qhov kawg thiab suav nrog 217 cov neeg mob uas muaj ntshav siab refractory ( zaum SBP 140-169 mmHg, noj ntau dua lossis sib npaug rau 3 cov tshuaj tiv thaiv hypertensive nrog rau cov tshuaj diuretics) los ntawm 722 lub teb chaws tshawb fawb. Cov txiaj ntsig tau luam tawm hauv The Lancet thaum Lub Peb Hlis 2026: Lub 24-teev dynamic systolic ntshav siab ntawm Saxdrostat 2 mg pawg poob los ntawm 16.6 mmHg; Cov placebo hloov kho qhov sib txawv yog -14.0 mmHg (95% CI -17.2 txog -10.8, p<0.0001).

 

71% ntawm Baxdrostat kho cov neeg mob muaj 24-teev dynamic SBP qis dua 130 mmHg, piv rau tsuas yog 17% hauv pawg placebo; Qhov txo qis hauv cov ntshav siab systolic thaum hmo ntuj los ntawm 13.9 mmHg (tseem suav nrog) tseem ceeb hauv kev kho mob tseem ceeb hauv kev txo qis kev pheej hmoo ntawm cov kab mob plawv cuam tshuam nrog kev kub siab thaum hmo ntuj.

 

Kev qhib lub sijhawm tshiab

 

Tom qab FDA pom zoo, thoob ntiaj teb cov hlab plawv hauv zej zog tau teb zoo siab. Cov ntaub ntawv hloov tshiab los ntawm American College of Cardiology (ACC) hais tias baxdrostat yog thawj aldosterone synthase inhibitor nkag mus rau hauv Asmeskas kev ua lag luam, kos npe rau lub sijhawm tshiab ntawm precision mechanism cuam tshuam hauv kev kho mob ntshav siab.

 

Kev tshuaj xyuas ib txhij ntawm BaxHTN luam tawm los ntawm NEJM, sib sau ua ke los ntawm xibfwb Tomasz J. Guzik ntawm Glasgow University thiab xibfwb Maciej Tomaszewski ntawm Manchester University, tau taw qhia meej tias: "Yog tias ua raws- kev tshawb fawb tuaj yeem qhia meej tias cov neeg mob twg tau txais txiaj ntsig ntau tshaj plaws, qhia meej txog qhov sib piv nrog MRA, tsim kom muaj kev soj ntsuam thaum ntxov 2} cov xwm txheej tsis ntev los no, cov ntaub ntawv, ASI yuav tsum tau hloov los ntawm kev cog lus adjuvant kev kho mob mus rau lub hauv paus tseem ceeb ntawm txoj kev kho mob rau intractable kub siab, yog li txhawb kev txhawb siab dav ntawm natriuresis lub tswv yim hauv kev tswj ntshav siab.

 

Lub vev xaib raug cai ntawm UCL Biomedical Research Center tseem hais ntxiv tias xibfwb Williams soj ntsuam cov ntaub ntawv ntawm BaxHTN yog "kev nce qib tseem ceeb hauv kev nkag siab thiab kho nyuaj rau kev tswj ntshav siab hauv kev txo cov ntshav siab, ua rau muaj kev cia siab rau kev kho mob zoo dua", thiab taw qhia tias qhov txo qis hauv systolic ntshav siab txog 10 mmHg cuam tshuam nrog kev txo qis hauv cov kab mob hauv lub raum, myocardial tsis ua haujlwm.

 

Kev nyab xeeb: Zuag qhia tag nrho zoo, nrog rau kev saib xyuas ntawm electrolyte

 

Both Phase III studies have confirmed that Baxdrostat has good safety and tolerability, with no occurrence of adrenal insufficiency or severe liver and kidney damage. In the BaxHTN study, the discontinuation rate due to hyperkalemia was 0.8% in the 1 mg group and 1.5% in the 2 mg group; The confirmed incidence of events with blood potassium levels>6 mmol / L hauv kev tshawb fawb Bax24 yog 3% (0% hauv pawg placebo).

 

Innovation nyob rau hauv txoj kev kho mob rau refractory hypertension

 

Tau ntev, cov kev kho mob rau refractory ntshav siab tau txwv tsis pub tshaj - ntxiv spironolactone rau kev kho triple yog "kab kawg ntawm kev tiv thaiv", tab sis spironolactone muaj kev phiv loj xws li txiv neej lub mis loj hlob, kev sib deev tsis zoo, hyperkalemia, thiab tsis xaiv rau CYP11B1. Lub community launch ntawm Baxdrostat muab ib qho kev xaiv tshiab nrog cov txheej txheem nce siab thiab kev xaiv ntau dua, uas xav tias yuav npog cov pej xeem nrog txwv tsis pub siv MRA ib txwm siv, xws li cov neeg uas muaj CKD thiab cov poov tshuaj siab.

 

NEJM tshuaj xyuas ntxiv hais tias cov kauj ruam tom ntej ntawm kev tshawb fawb yuav tsum tau tsom mus rau "cov neeg mob twg feem ntau yuav tau txais txiaj ntsig" - tshwj xeeb tshaj yog cov neeg mob uas muaj kev nyiam rau thawj aldosteronism (PA), CKD cov neeg mob ntshav siab, thiab cov neeg mob ntshav siab uas muaj qhov sib npaug ntawm aldosterone / renin ratios. Qhov no nteg lub hauv paus rau yav tom ntej cov tswv yim antihypertensive uas coj los ntawm aldosterone biomarkers.

 

Muaj peev xwm nthuav tawm cov lus qhia tshaj qhov kub siab

 

AstraZeneca tau nthuav dav kev tshawb fawb soj ntsuam ntawm Baxbendy mus rau ntau qhov chaw:

· Primary aldosteronism (PA): Raws li kev kho mob monotherapy, nws xav tias yuav hloov kev tswj xyuas kev sib txuas hauv lub sijhawm ntev - lub sijhawm tos ua ntej;

· Cov kab mob raum ntev (CKD) nyuaj nrog kev kub siab: kev tshawb fawb sib koom nrog SGLT2 inhibitor Farxiga tab tom pib;

· Kev tiv thaiv lub plawv tsis ua hauj lwm: kev tshawb nrhiav kev tiv thaiv rau cov neeg mob ntshav siab thiab lub plawv tsis ua haujlwm subclinical.

AstraZeneca cia siab tias Baxbendy qhov kev muag khoom siab tshaj plaws nyob rau hauv qhov ntsuas kub siab kom ncav cuag $ 5 nphom, thiab yog tias ua tiav tau nthuav dav mus rau thaj chaw xws li CKD thiab lub plawv tsis ua haujlwm, qhov kev muag khoom siab tshaj plaws tuaj yeem ncav cuag $ 10 billion.

 

Kev nce qib thiab kev soj ntsuam zoo nyob hauv Suav teb

 

Thaum Lub Ob Hlis 2026, Baxdrostat tau thov rau npe hauv Suav teb thiab tam sim no nyob rau hauv NMPA tshuaj xyuas theem. Raws li kev coj ua ntawm Tuam Tshoj txoj kev tshuaj xyuas qhov tseem ceeb thiab kev pom zoo channel, lub hom phiaj lub sijhawm txwv rau kev tshuaj xyuas qhov tseem ceeb yog li 130 hnub ua haujlwm (kwv yees li 6 lub hlis).

Qhov kev faib ua feem ntawm kev tswj tsis tau cov ntshav siab nyob rau hauv Suav teb tseem siab. Yog tias kwv yees raws li 10% feem pua ​​​​ntawm refractory hypertension, muaj ntau dua 20 lab tus neeg tau txais txiaj ntsig hauv Suav teb. Tsis tas li ntawd, qhov kev faib ua feem ntawm aldosterone ntau dhau hauv ntshav qab zib thiab CKD cov neeg mob hauv Suav teb kuj tseem siab, thiab Baxfendy cov txiaj ntsig ob rau pab pawg tshwj xeeb no yuav tsum tau txheeb xyuas ntxiv los ntawm kev tshawb fawb hauv zos.

Baxdrostat tsis yog ASI nkaus xwb tam sim no tab tom txhim kho. Lorundrostat los ntawm Mineralys Therapeutics kuj tseem nyob hauv FDA tshuaj xyuas theem (nrog rau lub hom phiaj tshuaj xyuas hnub tim 22 Lub Kaum Ob Hlis 2026). Baxdrostat tau tsim ib txoj haujlwm tseem ceeb hauv ASI taug qab nrog nws ib nrab ntev dua -lub neej, kev pab them nqi zoo 24-teev, thiab pom zoo thawj qhov zoo dua hauv kev ua lag luam.

 

Kev tshaj tawm ntawm Baxfengy yog ib qho tseem ceeb ntawm kev ua haujlwm ntawm cov tshuaj kub siab hauv 20 xyoo dhau los. Nws tsis tsuas yog ua rau qhov sib txawv ntawm kev kho mob loj ntawm refractory thiab tsis tuaj yeem tswj tau cov ntshav siab, tab sis kuj tseem qhib cov kev taw qhia tshiab rau kev kho mob ntshav siab nrog cov txheej txheem lom neeg tshiab - inhibiting aldosterone overproduction los ntawm cov hauv paus hniav. Txoj kev kho tshiab no yuav tsum tau txais txiaj ntsig ntau lab tus neeg mob hauv Suav teb nrog kev tswj ntshav siab tsis zoo nyob rau yav tom ntej, muab riam phom muaj zog tshiab rau kev tiv thaiv thiab tswj cov kab mob plawv.