Merck evobrutinib: thawj BTK inhibitor los txo qis biomarkers tseem ceeb ntawm cov hlab ntaws / mob!

Lub chaw lag luam tshuaj German loj tshaj Merck (Merck KGaA) tsis ntev los no tau tshaj tawm cov ntaub ntawv los ntawm cov tshuaj placebo tswj sim theem ob sim ntawm 73th Lub Rooj Sib Tham Txhua Xyoo ntawm American Academy of Neurology (AAN) nyob rau xyoo 2021. Kev sim tau pom tias hauv ntau yam sclerosis (Hauv MS) cov neeg mob, qhov ncauj, xaiv heev BTK inhibitor evobrutinib kev kho mob txo qis ntshav neurofilament lub teeb saw (NfL) qib, uas yog lub biomarker tseem ceeb ntawm cov hlab ntaws puas thiab o.

Nws tsim nyog teev tias evobrutinib yog thawj zaug thiab tsuas yog BTK inhibitor uas tau ua pov thawj los txo cov biomarkers tseem ceeb ntawm cov hlab ntsha puas tsuaj thiab mob hauv MS cov neeg mob. Txhawb cov qib NfL hauv cov ntshav muaj feem xyuam nrog kev puas tsuaj thiab mob neuronal, thiab tuaj yeem kwv yees yav tom ntej lub hlwb atrophy thiab kab mob kev loj hlob.

Professor Jens Kuhle, Tus Thawj Coj ntawm Ntau Hom Sclerosis Center ntawm Tsev Kawm Ntawv University of Basel, Switzerland, tau hais tias: "Ntshav NfL yog biomarker uas tuaj yeem saib xyuas kev kis kab mob thiab kev kho mob teb. Qhov no yuav yog qhov hnyav dua thiab tsis yooj yim dua lwm cov qauv ntsuas mob rau cov neeg mob MS. Cov ntaub ntawv no muab kev nkag siab tseem ceeb rau lub luag haujlwm ntawm evobrutinib hauv kev tswj hwm kev kho mob ntawm ntau tus mob sclerosis, thiab qhia ntxiv tias qhov inhibition ntawm BTK los ntawm evobrutinib tuaj yeem txo cov ntaub so ntswg uas cuam tshuam nrog ntau tus sclerosis."

Hauv qhov kev tso tshuaj no rau theem II sim ntawm evobrutinib hauv cov neeg mob uas rov huam mob ntau yam sclerosis (RMS), kev soj ntsuam tom qab tau soj ntsuam 166 cov neeg mob uas muaj lub hauv paus NfL qhov tseem ceeb thiab tsawg kawg ib qho nqi qis NfL tus nqi. Cov ntaub ntawv qhia tau hais tias piv nrog cov placebo pab pawg, evobrutinib 75mg BID (ob zaug ib hnub) pawg muaj qhov tus kwv tij txo qis tshaj hauv NfL qib hauv qib 12 thiab 24 lub lis piam. Tam sim no, kev noj tshuaj ob zaug ob zaug ib zaug nrog 75mg BID sib npaug raug ntsuas nyob rau hauv Txheej Xwm III, uas npaj yuav ua kom tiav cov neeg mob hauv 2021.

Cov txiaj ntsig tseem ceeb los ntawm kev tshawb fawb qib II no tau tshaj tawm hauv New England Journal of Medicine hauv 2019. Vim tias qhov NfL nce ntxiv yog cuam tshuam nrog cov chaw kuaj mob tsis taus thiab mob hlwb ntawm MS, cov txiaj ntsig no, ua ke nrog cov ntaub ntawv sim ua ntej dhau los uas tau lees tias qhov txo qis ntawm T1 Gd + qhov txhab thiab qhov ua kom rov zoo txhua xyoo (ARR), txhawb ntxiv rau qhov kev xav tias qhov inhibition ntawm BTK nrog evobrutinib kuj tseem tuaj yeem cuam tshuam rau hauv nruab nrab lub paj hlwb. O ua ntu zus thiab nce qib ntawm MS hauv cov hlab hlwb (CNS).

Hauv lwm qhov ncauj lus tshaj tawm ntawm AAN lub rooj sib tham txhua xyoo, BTK thiab qib (phosphorylated) BTK (pBTK) hauv B hlwb cais los ntawm RMS cov neeg mob tau kuaj. Cov txiaj ntsig ntxiv txhawb cov nyhuv ntawm evobrutinib ntawm CNS pathology ntawm MS cov neeg mob. pBTK yog qhia tau zoo nyob rau hauv B ntawm pob ntawm cov neeg mob RMS, suav nrog kev nco B hlwb hais tawm T-bet thiab CXCR3. Evobrutinib txo cov kev tsiv teb tsaws chaw ntawm CXCR3 B cim xeeb B hlwb los ntawm tib neeg CNS endothelial cell monolayer, tawm tswv yim tias evobrutinib tuaj yeem cuam tshuam cov kev ua ntawm pathogenic B hlwb thiab tswj cov kev nce qib ntawm MS.

Tsis tas li ntawd, kev tshawb nrhiav kev tshawb nrhiav yuav tshaj tawm ntawm triMS lub rooj sib tham hauv online nyob rau lub Tsib Hlis 27 tau soj ntsuam qhov sib txheeb ntawm kev faib tawm ntawm evobrutinib hauv cerebrospinal kua (CSF) ntawm RMS cov neeg mob thiab lub plasma concentration. Kev kuaj ntshav plasma thiab cerebrospinal tau sau los ntawm ib pawg me me ntawm MS cov neeg mob kho nrog 75 mg BID hauv Kev Tshawb Nrhiav Phase II Qhib Ntev (OLE) kawm. Evobrutinib raug kuaj pom ntawm cov kua dej cerebrospinal ntawm txhua tus neeg mob suav nrog hauv kev txheeb xyuas (n=9). Qhov kev tso siab ntawm cerebrospinal kua hauv lub hauv paus yog tib yam li cov ntshav pub dawb. Qhov no qhia tau hais tias ntxiv rau kev tshuaj tiv thaiv BTK ntawm lub hlwb peripheral, evobrutinib kuj tseem yuav inhibit B hlwb thiab myeloid hlwb nthuav qhia BTK hauv CNS, uas yuav cuam tshuam cov kev muaj mob ntawm MS.

Danny Bar Zohar, MD, Ntiaj Teb Lub Taub Hau ntawm Kev Tsim Kho Kev Lag Luam ntawm Merck Healthcare, tau hais tias: "Feem ntau, cov ntaub ntawv hais tawm tam sim no thiab cov ntaub ntawv soj ntsuam qhia tau hais tias evobrutinib tuaj yeem tiv thaiv MS cov kev koom tes hauv kev ua kab mob thiab kev vam meej. Ib qhov ntxiv rau, lub nruab nrab ntawm lub paj hlwb tau luam tawm thiab nthuav tawm. Cov yam ntxwv ntawm kev nkag mus hauv lub cev thiab tus lej nyob BTK siab heev, cov kev tshawb pom no txuas ntxiv pom zoo muaj peev xwm ntawm evobrutinib kev kho mob ntawm cov neeg mob uas muaj ntau yam sclerosis."

Tus qauv tshuaj lom neeg ntawm evobrutinib (duab los ntawm: medchemexpress.cn)

Ntau tus mob sclerosis (MS) yog ib hom mob mus ntev rau lub nruab nrog hlab hlwb thiab cov feem ntau tsis mob, ua kom mob hlwb rau cov neeg hluas. Khwv yees tias kwv yees li ntawm 2.8 lab tus tib neeg thoob ntiaj teb tau txais ntau yam mob sclerosis. Txawm hais tias cov tsos mob yuav txawv, cov tsos mob feem ntau ntawm MS suav nrog ua rau pom kev plooj plooj, loog lossis ntog hauv qhov kawg, thiab lub zog thiab kev ua kom muaj teeb meem. Txoj kev rov ua ntau hom sclerosis yog qhov ntau tshaj.

Evobrutinib (M2951) tam sim no nyob hauv kev kho mob hauv tsev kho mob los tshawb txog nws lub peev xwm uas yog kev kho mob rau ntau yam sclerosis (MS). Cov tshuaj yog qhov ncauj, xaiv heev inhibitor ntawm Bruton' s tyrosine kinase (BTK). BTK ua lub luag haujlwm tseem ceeb hauv kev tsim kho thiab ua haujlwm ntawm ntau yam kabmob muaj zog tiv thaiv kab mob nrog rau B lymphocytes thiab macrophages.

Evobrutinib yog tsim los txwv qhov kev cuam tshuam loj ntawm B ntawm tes, xws li nthuav tawm, tso cov tshuaj tiv thaiv thiab cytokines, tsis cuam tshuam ncaj qha rau T cell. BTK inhibition ntseeg tau tias yuav inhibit autoantibody-ua cov hlwb. Kev tshawb fawb qhia paub tau pom tias BTK inhibition yuav muaj kev kho mob rau qee yam kab mob autoimmune. Tam sim no, lub ntiaj teb theem III kev txhim kho kev kho mob siab yog ntsuas evobrutinib rau kev kho mob ntawm MS. Lub phiaj xwm suav nrog 2 qhov kev tshawb fawb tseem ceeb nyob rau theem III, EVOLUTION RMS 1 thiab 2. Evobrutinib tab tom muaj kev txhim kho hauv chaw kho mob thiab tsis tau pom zoo los ntawm ib lub tebchaws.