Merck kis tau tus IAP kev thaiv rau ze li $ 1.1 nphom

Tsis ntev los no, Merck ntawm lub tebchaws Yelemees tshaj tawm tias nws tau kos npe rau daim ntawv pom zoo tso cai rau kev txhim kho thiab kev lag luam xevinapant (Debio1143) nrog Debiopharm. Raws li cov ntsiab lus ntawm daim ntawv cog lus tso cai, German Merck yuav tau txais txoj kev tsim tshwj xeeb thoob ntiaj teb thiab kev ua lag luam ntawm xevinapant, thiab yuav sib koom ua ke rau ntu 3 txuas ntxiv rau kev kawm TrilynX nrog Debiopharm. , CRT) raws li kev ua tau zoo thiab kev nyab xeeb ntawm xevinapant thiab cov placebo. Nyob rau tib lub sijhawm, Debiopharm tau txais cov nyiaj them ua ntej ntawm 188 lab euros (227 lab nyiaj daus las) thiab cov nyiaj tseem ceeb thiab cov nqi ntau txog 710 lab euros (856 lab nyiaj daus las Meskas). Daim ntawv cog lus tseem suav nrog txoj cai los tsim cov kev sib txuas ua ke ntawm cov txuas ntxiv rau xevinapant Cov.

Nws nkag siab tias Xevinapant yog" muaj peev xwm; thawj-hauv-chav" muaj zog, qhov ncauj inhibitor ntawm apoptosis protein (IAP) antagonist. Tam sim no nyob rau theem tseem ceeb 3 kev soj ntsuam kawm, kev sib txuas ntawm platinum-muaj cov tshuaj kho mob thiab cov fractionation siv tshuaj kho hluav taws xob (cov qauv fractionation siv hluav taws xob) rau yav tas los tsis muaj kev pheej hmoo nyob hauv zos ua kom zoo taub hau thiab caj dab txhaws qog cell carcinoma (LA SCCHN) cov neeg mob Cov.

Txog tam sim no, tsis muaj IAP antagonist tau pom zoo rau kev lag luam hauv ntiaj teb, thiab xevinapant yog tam sim no ib qho ntawm kev loj hlob sai sai IAP antagonist khoom hauv ntiaj teb. Yav dhau los, xevinapant tau txais kev tso cai tshuaj pom zoo los ntawm US FDA. Cov txiaj ntsig ntawm kev sib tw, pom qhov muag tsis pom tseeb theem 2 qhov kev tshawb fawb pom tau tias qhov sib ntxiv ntawm xevinapant rau tus txheej txheem kev kho mob CRT txhim kho hauv cheeb tsam kev tswj hwm hauv thaj tsam ntawm 18 lub hlis. 21%, lub ntsiab lus tseem ceeb, tau mus txog hauv qhov xaus. Muab piv nrog pab pawg tswj hwm, qhov tseem ceeb tau txais txiaj ntsig tsis pub muaj kev ciaj sia (PFS) tau pom kuj tau pom tom qab kev soj qab taug qab 2 xyoo. Ntawm 3-xyoo rov qab, xevinapant ua ke nrog CRT qhia txog kev txheeb xyuas 51% txo qis kev pheej hmoo ntawm kev tuag piv nrog cov placebo ua ke nrog CRT.

Nyob rau theem no, ntxiv rau kev kho mob tam sim no III, kev soj ntsuam kab mob xevinapant rau kev kho ntau yam mob qog tab tom ua haujlwm, suav nrog cov tsis mob qog nqaij hlav hauv lub ntsws, mob qog ntawm zes qe menyuam, mob qog taub hau thiab caj dab, thiab lwm yam.

Nws tseem tsim nyog pom tias cov ntaub ntawv xov xwm pej xeem qhia tau hais tias xevinapant thaum xub thawj npe hu ua AT-406, uas tau hloov los ntawm tus thawj ntawm Yasheng Tshuaj mus rau Debiopharm ntawm Switzerland xyoo 2011. Hauv cov khoom lag luam tam sim no tso tawm rau ntawm Yasheng Pharmaceutical lub vev xaib, ib qho ntawm cov khoom lag luam yog npe AT-406. IAP antagonist, APG-1387, tam sim no nyob rau hauv qhov txheej txheem kev kho mob. Cov cim tseem ceeb yog cov qog ua hlav (ua ke nrog kev tiv thaiv qog noj ntshav) thiab mob siab B. Ob leeg yog nyob rau theem ob ntawm kev kuaj mob nyob rau theem ob. Nws tseem yog thawj zaug hauv Suav teb kom nkag mus rau hauv chav kuaj mob. IAP inhibitors.

IAP protein tau qhia tau zoo heev thiab cuam tshuam nrog ntau yam mob qog nqaij hlav, suav nrog mob qog nqaij hlav cancer, mob taub hau thiab caj dab, mob cancer mis, mob plab hnyuv, nrog rau melanoma thiab ntau yam mob myeloma, thiab muaj feem cuam tshuam nrog kev kuaj mob. Yog li, IAPs yog qhov kev taw qhia tseem ceeb rau kev txhim kho cov tshuaj tiv thaiv qog noj ntshav.

Ntxiv rau ob qhov tshuaj tiv thaiv IAP no, tseem muaj ntau cov kev tshawb fawb cov khoom hauv cov chaw tsim kho cov qauv thoob ntiaj teb, suav nrog LCL161, GDC-0152, TL32711 (Birinapant), BI 891065, thiab lwm yam, piv txwv li, LCL161 yog tsim los ntawm Novartis, thiab nws tuaj yeem sib cuam tshuam nrog cIAP1 thiab cIAP2 Lub chaw BIR3 khi rau thiab ua rau autoubiquitination thiab tiv thaiv proteasomal kev cuam tshuam ntawm cIAP1 thiab cIAP2, ua rau kom muaj kev ua haujlwm ntawm tsis-tus qauv NF-B cov paib ntawm txoj hauv kev thiab kev tsim cov qog nqaij hlav necrosis factor. Tam sim no, ib tug xov tooj ntawm cov kev tshawb fawb soj ntsuam ntawm LCL161 yog nyob rau hauv kev kawm.

Ntxiv rau, IAP inhibitors ua ke nrog lwm tus neeg sawv cev tseem ceeb ntawm kev tiv thaiv kab mob qog noj ntshav, kev tiv thaiv kab mob hauv lub cev tiv thaiv kab mob, kuj tau dhau los ua ib qho ntawm cov kev qhia tseem ceeb ntawm kev txhim kho hauv chaw kho mob, thiab ntau cov kev kho mob tseem niaj hnub ua.

Xyoo tas los' s ASCO, thawj cov ntaub ntawv ntawm IAP inhibitors Birinapant thiab Debio1143 nrog PD-1 / PD-L1 cov tshuaj tiv thaiv tau tshaj tawm. Ntawm 4 tus neeg mob MSS plob tsis so tswj mob tau kho nrog Birinapant ua ke nrog PD-1 antibody Pembrolizumab, 1 tus neeg mob ua tiav ncua ntev ib nrab ntawm kev tshem tawm; ntawm 5 cov neeg mob NSCLC raug kho nrog Debio1143 ua ke nrog PD-L1 tiv thaiv Avelumab, 3 tus neeg mob tsom ntau dua 15% ntawm cov qog ua haujlwm tsawg, thiab ib tus neeg mob qis PD-L1 qhia tau ua tiav cov kab mob ntev ntev. Cov ntaub ntawv no qhia tias MSS tiv thaiv mob hnyuv tsis cuam tshuam nrog PD-1 cov tshuaj tiv thaiv, thiab NSCLC uas tsis qhia PD-L1 yuav tau txais txiaj ntsig los ntawm hom kev sib txuam no.