AstraZeneca / Amgen TSLP Lub Hom Phiaj Monoclonal Antibody Tezepelumab Theem 3 Kev Sim Ua Tau Zoo

AstraZeneca thiab nws tus khub Amgen nyuam qhuav sib koom ua ke tshaj tawm cov txiaj ntsig zoo ntawm Theem 3 NAVIGATOR kev sim tshuaj tiv thaiv tshuaj tezepelumab rau kev kho mob hawb pob tsis tau zoo. Tezepelumab yog qhov muaj peev xwm ua thawj-hauv tshuaj uas tuaj yeem tiv thaiv qhov cuam tshuam ntawm thymic interstitial lymphopoietin (TSLP), uas yog epithelial cytokine uas ua lub luag haujlwm tseem ceeb hauv kev mob ntsws asthma.

NAVIGATOR yog thawj theem III kev sim ua kom pom cov txiaj ntsig kho qhov tseem ceeb ntawm kev tsom rau TSLP rau kev mob ntsws asthma: nyob rau hauv cov pej xeem ntau ntawm cov neeg mob hawb pob mob hnyav, tezepelumab ua rau muaj kev cuam tshuam txog kev mob ntsws thiab mob ntshav qab zib ua kom mob hawb pob ntau ntxiv, suav nrog cov neeg mob eosinophils uas tsis tshua muaj mob.

Cov ntaub ntawv qhia tias qhov kev tshawb fawb tau mus txog qhov kawg: hauv tag nrho cov neeg mob, piv nrog cov placebo + cov txheej txheem kev saib xyuas (SoC), tezepelumab + SoC kev kho mob ua rau 52-lub limtiam kev mob hawb pob tau zoo (AAER) ) cov ntsiab lus tseem ceeb thiab thaj chaw hauv nroog loj Cov kev txo qis. Hauv qhov kev sim no, SoC yog ib qho tshuaj nruab nrab lossis koob tshuaj hnoos corticosteroid (ICS) ntxiv rau ib qho tshuaj tswj ntxiv, nrog lossis tsis siv tshuaj corticosteroids (OCS).

Tsis tas li ntawd, nyob hauv pawg me ntawm cov neeg mob nrog lub hauv paus eosinophil suav ntawm< 300="" hlwb="" microliter,="" qhov="" kev="" sim="" tseem="" tau="" mus="" txog="" qhov="" kawg="" ntawm="" qhov="" kawg:="" piv="" nrog="" cov="" placebo="" +="" soc,="" tezepelumab="" +="" soc="" kev="" kho="" mob="" ua="" rau="" aaer="" cov="" xwm="" txheej="" ntawm="" lub="" ntsiab="" lus="" tseem="" ceeb="" thiab="" qhov="" txo="" qis="" ntawm="" qhov="" tseem="" ceeb="" hauv="" chaw="" khomob.="" kev="" txo="" tawm="" zoo="" sib="" xws="" hauv="" aaer="" tau="" pom="" nyob="" hauv="" pawg="" neeg="" mob="" ntawm="" cov="" neeg="" mob="" nrog="" lub="" hauv="" paus="" eosinophil="">< 150="" hlwb="">

Hais txog kev nyab xeeb, tezepelumab muaj kev tiv thaiv zoo rau cov neeg mob uas mob hawb pob hnyav. Cov kev ntsuas ua ntej pom tau hais tias tsis muaj qhov sib txawv hauv kev kho mob hauv kev nyab xeeb tau los ntawm tezepelumab kho pawg thiab pab pawg placebo. Cov txiaj ntsig ntawm kev sim yuav raug tshaj tawm hauv kev sib tham txog kev kho mob.

Hawb pob mob hnyav yog tus kab mob ua rau mob hnyav, cuam tshuam rau kwv yees li 34 lab tus tib neeg thoob ntiaj teb. Txawm hais tias siv cov tshuaj tiv thaiv kev mob hawb pob ntau heev, tam sim no muaj cov kev siv tshuaj lom neeg thiab OCS, ntau tus neeg mob hawb pob hnyav txuas ntxiv cov tsos mob thiab nquag zuj zus.

Tus xibfwb Andrew Menzies-Gow, tus thawj coj tshawb xyuas ntawm NAVIGATOR kev sim siab thiab tus thawj coj ntawm Lub Tsev Haujlwm Pulmonary ntawm Royal Brompton Tsev Kho Mob hauv London, UK tau hais tias: "Vim muaj kev nyuaj ntawm mob hawb pob loj, txawm hais tias tau txais kev saib xyuas cov tshuaj nqus tau thiab tam sim no tau pom zoo cov tshuaj lom , ntau tus neeg mob tseem niaj hnub ua qhov tsis zoo Lub txiaj ntsig ntawm kev kawm tshawb nrhiav niaj hnub no qhia tau hais tias tezepelumab muaj qhov hloov pauv txoj kev saib xyuas ntawm feem ntau ntawm cov neeg mob uas muaj mob hawb pob loj uas tam sim no tsis tau txais kev pab, suav nrog cov tsis muaj eosinophilic phenotype."

Mene Pangalos, Tus Thawj Coj ntawm R& D ntawm AstraZeneca Biopharmaceuticals, tau hais tias:" Cov nyhuv ntawm tezepelumab txawv ntawm lwm cov kev mob ntsws asthma. Nws lub hom phiaj ntawm kev ua yog ntau txoj hauv kev, uas tuaj yeem ua rau mob hawb pob thiab ua kom tsaus muag. Cov ntaub ntawv zoo siab tau coj peb mus ib kauj ruam ntxiv rau kev muab tshuaj rau cov neeg mob ua tsis taus pa hnyav, suav nrog cov neeg tsawg eosinophil."

Tezepelumab: tsim rau ntau cov pab pawg neeg mob hawb pob, yuav tsim tsa kom muaj cua daj cua dub hauv lub tshav pob ntawm hawb pob

TSLP yog ib qho epithelial cytokine tsim tawm los teb rau cov tshuaj tiv thaiv kab mob (xws li mob ntsws, cov kab mob, thiab lwm yam kab mob), thiab ua lub luag haujlwm tseem ceeb hauv kev tshwm sim thiab kev tawm tsam ntawm cov hlab pa. TSLP tsav tawm cov dej ntws tawm los ntawm T2 cytokines, suav nrog IL-4, IL-5 thiab IL-13, ua rau muaj kev o thiab mob hawb pob. TSLP kuj tseem tuaj yeem ua rau ntau hom hlwb koom nrog cov qog ua haujlwm tsis-T2. Yog li, qhov dej ntws ntxov ntawm TSLP hauv cov kis mob tau ua rau pom lub hom phiaj ntawm cov neeg mob hawb pob ntau. Thaiv TSLP tuaj yeem tiv thaiv cov kabmob tiv thaiv kab mob los ntawm kev tso tawm cytokines pro-inflammatory, yog li tiv thaiv hawb pob kom tsis txhob ua kom mob hawb pob thiab txhim kho kev tswj hwm mob hawb pob.

Tezepelumab yog thawj-chav kawm tiv thaiv TSLP monoclonal tshuaj tiv thaiv uas tshwj xeeb khi rau tib neeg TSLP thiab thaiv nws txoj kev cuam tshuam nrog cov receptor complex, yog li tiv thaiv kab mob tiv thaiv qog ua lub hom phiaj los ntawm TSLP Tso tawm pro-inflammatory cytokines tiv thaiv kev mob hawb pob thiab txhim kho kev tswj hwm hawb pob. Vim tias nws lub luag haujlwm hauv qhov dej ntws thaum ntxov, lub tezepelumab tuaj yeem tsim nyog rau ntau tus neeg mob uas muaj kev mob tsis muaj kev tswj hwm tus mob hawb pob, tsis hais tus neeg mob' s phenotype lossis T2 biomarker xwm txheej.

Raws li kev kawm theem IIb PATHWAY kev tshawb fawb, tezepelumab muaj cov ntsiab lus tseem ceeb thiab thaj chaw kho mob txo qis hauv cov mob hawb pob ntau dua rau cov neeg mob hawb pob mob hnyav nrog lub hauv paus eosinophil suav ntawm< 300="" hlwb="" μl.="" tsoom="" fwv="" teb="" chaws="" asmeskas="" fda="" tso="" cai="" tezepelumab="" xyoo="" 2018="" kev="" sib="" tw="" tshuaj="" yeeb="" tshuaj="" kho="" mob="" (btd)="" rau="" kev="" kho="" mob="" rau="" cov="" neeg="" mob="" uas="" muaj="" mob="" hawb="" pob="" hnyav="" yam="" tsis="" muaj="" cov="" tshuaj="" eosinophilic="">

Tam sim no, tezepelumab tab tom raug tsim los ntawm AstraZeneca thiab Amgen. Kev lag luam ntseeg hais tias yog tezepelumab ua tiav kev lag luam, nws yuav teeb tawm ntawm cov cua daj cua dub hauv kev kho mob hawb pob, thiab nws cov pej xeem kev kho mob yuav loj dua li cov kev kho mob tam sim no, suav nrog GlaxoSmithKline (GSK) Nucala (mepolizumab, tsom mus rau IL -5), Teva Cinqair (reslizumab, phiaj rau IL-5), thiab tam sim no tab tom tsim tshuaj lom neeg rau kev kho mob hawb pob, xws li AstraZeneca tus kheej benralizumab (hom phiaj IL-5 receptor α subunit [IL-5Rα]) thiab Sanofi lub Dupixent (hom phiaj IL-4 / IL-13), tag nrho plaub qhov kev kho mob tsuas yog tsom cov tshwj xeeb cov tshuaj loog uas ua rau mob hawb pob, thiab tsuas yog tsim rau qee yam kev mob ntsws asthma, uas yog, ib pawg neeg mob ntawm cov neeg mob. Xws li eosinophilic hawb pob.