Merck's P2X3 Receptor Antagonist Gefapixant Tau Ua tiav Ob Theem III Kev Ntsuam Xyuas Zoo

Merck& Co tsis ntev los no tshaj tawm cov txiaj ntsig ntawm ob theem tseem ceeb III kev soj ntsuam kuaj mob (COUGH-1, COUGH-2) ntawm kev hnoos tshuaj tiv thaiv kab mob hnoos qeev (MK-7264) hauv kev txhim kho. Gefapixant yog qhov ncauj, xaiv P2X3 receptor antagonist uas tau tsim kho rau kev kho mob refractory mob hnoos (RCC) lossis mob hnoos uas tsis paub meej (UCC). Tam sim no, tsis muaj kev pom zoo kho thiab tshuaj rau RCC thiab UCC.

COUGH-1 thiab COUGH-2 yog thawj zaug Kev Ntsuam Siab Ntu 3 kev sim rau hauv cov neeg laus RCC thiab UCC cov neeg laus. RCC yog hais txog kev hnoos uas ua mob txawm tias kev kho tus mob hauv lub cev, thaum UCC hais txog qhov hnoos uas nws tus cag tsis tuaj yeem txiav txim tau txawm hais tias muaj kev soj ntsuam zoo.

Gefapixant tshuaj qauv (daim duab duab: medchemexpress.com)

Cov txiaj ntsig tau pom tias txoj kev tshawb no tau mus txog qhov kawg: suav nrog cov placebo pab pawg, qhov hnoos hauv pawg kho mob gefapixant li ntawm 45 mg ob zaug ib hnub nyob rau 12 lub lim tiam (COUGH-1 txoj kev kawm) thiab 24 lub lim tiam ( COUGH-2 txoj kev tshawb nrhiav) (Siv teev 24 teev los ntsuas qhov tseeb ntawm tus naj npawb ntawm hnoos ib teev) muaj kev txo qis ntawm kev txheeb suav. Nws yog tsim nyog sau cia tias nyob hauv ob txoj kev tshawb nrhiav, pawg kho mob gefapixant nrog ib koob tshuaj 15 mg ob zaug ib hnub twg tsis tau ncav cuag thawj qhov kev ua tau zoo.

Cov ntaub ntawv tshwj xeeb muaj raws li hauv qab no: (1) Hauv qhov kev tshawb nrhiav COUGH-1, ntawm 12 lub lim tiam ntawm kev kho mob, piv nrog cov pab pawg placebo, qhov ntau zaus hnoos hauv pawg kho nrog gefapixant ntawm koob ntawm 45 mg ob zaug ib hnub yog qhov tseem ceeb txo los ntawm 18.45% (95% CI: -32.92 txog -0. 86; p=0.041); (2) Hauv COUGH-2 txoj kev tshawb nrhiav, ntawm 24 lub lim tiam ntawm kev kho mob, piv nrog pab pawg placebo, 24 teev ntawm kev hnoos ntawm 45 mg koob tshuaj ntawm gefapixant ob zaug ib hnub tau raug txo qis los ntawm 14.64% (95% CI) : -26.07 txog -1.43; p=0.031). Qhov nruab nrab, cov neeg mob uas tau noj 45 mg ntawm cov tshuaj gefapixant ib hnub ob zaug muaj 62% txo qhov hnoos tsawg dua piv rau qhov pib hauv COUGH-1 kev sim thiab 63% txo qhov hnoos tsawg dua piv rau cov hauv paus hauv qhov COUGH-2 sim.

Qhov xaus ob theem siab txhawb qhov kev pom tseem ceeb ntawm txoj kev kawm. Thaum sawv ntxov qhov hnoos thaum sawv ntxov feem ntau zoo ib yam li 24 xuaj moos qhov hnoos tau tshwm sim. Pawg 45 mg koob tshuaj ib hnub ob zaug tau txog qhov tseem ceeb ntawm qhov kev tshawb fawb COUGH-2 (kwv yees kwv yees kev txo qis 15.79%, 95% CI: -27.27 txog -2.50; p=0.022) Muaj qhov sib txawv ntawm txoj kev tshawb fawb COUGH-1 ( kwv yees kwv yees kev txo qis 17.68%, 95% CI: -32.5 txog 0.50; p=0.056). Hauv lub lis piam 24, piv nrog pab pawg placebo, pawg 45 mg koob tshuaj ib hnub ob zaug muaj kev txhim kho tseem ceeb hauv kev ua lub neej zoo hnoos (HR=1.41, p=0.042). Ntawm cov neeg mob hauv 45 pawg koob tshuaj mg, 77.1% ntawm cov neeg mob muaj qib tseem ceeb hauv chav kho mob hauv lub neej muaj feem ntsig txog hnoos (ntsuas los ntawm LCQ).

Hauv 2 qhov kev tshawb fawb, kev nyab xeeb thiab tiv taus ntawm gefapixant yog zoo ib yam nrog cov ntaub ntawv tshawb fawb dhau los. Qhov xwm txheej ntawm qhov tshwm sim tsis zoo yog qhov zoo sib xws hauv txhua pawg (GG lt; 4%). Qhov ntau zaus ntawm kev txiav tawm ntawm 45mg pawg vim tias qhov xwm txheej tsis zoo dua thiab qhov tshwm sim ntawm saj-cuam tshuam cov xwm txheej tau ntau dua. Feem ntau cov kev cuam tshuam txog saj tau tsis txaus mus rau qhov nyhav.

Cov txiaj ntsig saum toj no tau tshaj tawm ntawm 2020 European Respiratory Society (ERS) International Kev Sib Tham. Merck npaj yuav los qhia COUGH-1 thiab COUGH-2 cov ntaub ntawv tshawb fawb nrog cov chaw tswj hwm thoob ntiaj teb.

Nws kwv yees tias 5% -10% ntawm cov neeg laus hauv ntiaj teb raug mob hnoos ntev. Ib txhia ntawm cov neeg mob no yog hnoos refractory ntev (RCC) thiab qhia tsis tu ncua ntev hnoos (UCC), thiab lawv muaj kev cuam tshuam rau ntau yam chiv keeb uas feem ntau tsis ua rau hnoos hauv cov ncauj lus zoo. Qhov no suav nrog cov haujlwm txhua hnub (xws li sib tham thiab luag), qhov hloov ntawm qhov kub thiab txias, cuam tshuam rau aerosols lossis tsw ntxhiab ntawm cov zaub mov. Txog tam sim no, cov kev kho mob rau cov neeg mob no tsis tshua muaj siab, thiab ntau tus neeg mob tsis tau muaj kev pab ntau lub xyoo.

Xav txog qhov kev xav tau uas tsis txaus ntseeg ntawm cov neeg mob no, cov txiaj ntsig ntawm COUGH-1 thiab COUGH-2 txoj kev tshawb fawb tau txhawb nqa, pom tias gefapixant muaj peev xwm los muab cov kev xaiv kho tshiab rau cov neeg mob ntsib nrog lub nra ntawm tus kab mob no.

Dr. Roy Baynes, Tus Lwm Thawj Coj Thawj Coj thiab Lub Tuam Thawj ntawm Lub Chaw Saib Xyuas Kev Noj Qab Haus Huv Hauv Ntiaj Teb thiab Tus Thawj Saib Xyuas Kws Kho Mob ntawm Merck Research Laboratories, tau hais tias: Merck tau cog lus rau kev nkag siab tshawb nrhiav qhov muaj peev xwm ntawm gefapixant hauv cov neeg mob no. Ob qho ntawm ob qhov kev sim no tau mus txog lub cim kawg, uas yog, noj 45mg ntawm Gefapixant ob zaug hauv ib hnub nws txo qis ntau zaus ntawm hnoos hauv cov neeg mob no. Peb zoo siab uas muaj sijhawm los koom nrog kev tshawb fawb. Lub ntiaj teb los qhia cov ntaub ntawv no."