Novartis P-selectin Tus Kws Lij Choj Adakveo Tau Pom Zoo Thiab Pom Zoo Los Ntawm EU CHMP Thiab Tau Tso Npe Hauv 8 Lub Tebchaws!

Novartis tsis ntev los no tshaj tawm tias Lub Chaw Haujlwm Saib Xyuas Kev Noj Tshuaj hauv Tebchaws Europe (EMA) rau Cov Khoom Siv Tshuaj rau Cov Neeg Siv (CHMP) tau tshaj tawm cov lus pom zoo rau kev pom zoo pom zoo rau Adakveo (crizanlizumab) rau cov neeg mob uas muaj hnub nyoog 16 thiab tshaj rau cov neeg laus thiab cov menyuam yaus uas muaj mob cytological (SCD), txhawm rau tiv thaiv kom tsis txhob mob plawv ntu ob leeg (VOC) lossis kev nyuaj siab mob. Adakveo tuaj yeem raug siv los ua kev kho mob ntxiv rau hydroxyurea (HU / HC) lossis raws li kev kho mob rau cov neeg mob uas tsis haum rau HU / HC lossis muaj cov lus teb tsis txaus.

Tam sim no, cov lus pom zoo ntawm CHMP yuav rov saib xyuas los ntawm European Commission (EC), uas feem ntau ua qhov kev txiav txim siab zaum kawg li ntawm 2 hlis. Yog tias tau txais kev pom zoo, Adakveo yuav yog thawj qhov kev pab cuam kho mob hauv Europe uas tuaj yeem siv los tiv thaiv VOC hauv cov neeg mob SCD. VOC yog ib qho kev cia siab sai sai, tsis tuaj yeem tsis txaus ntseeg, thiab muaj feem cuam tshuam nrog kev pheej hmoo ntawm khoom nruab nrog cev thiab tuag taus. Cov ntaub ntawv soj ntsuam pom tias thaum ua ke nrog lossis tsis muaj kev kho mob hydroxyurea (HU / HC), Adakveo txo ​​qis cov VOCs ntau thiab txo qis cov neeg mob pw hauv tsev kho mob piv nrog cov placebo.

Adakveo tau txais lub ntiaj teb' s thawj cov pab pawg hauv Tebchaws Asmeskas thaum Lub Kaum Ib Hlis 2019. Cov tshuaj tau pom zoo nyob hauv Tebchaws Meskas thiab 7 lwm lub tebchaws rau kev siv rau cov neeg laus thiab cov menyuam yaus uas muaj mob SCD hnub nyoog 16 xyoo thiab laus dua los txo cov zaus ntawm VOC los yog kev ntxhov siab heev. Cov. Nws yog tsim nyog teev tias Adakveo yog thawj zaug thiab tsuas yog pom zoo tsom cov phiaj xwm uas muaj cov tshuaj kho tau los ntawm kev sib txuas nrog P-selectin. Hauv Tebchaws Asmeskas, FDA tau tso cai yav tas los Adakveo kev quav tshuaj yeeb dej caw thiab kev kuaj xyuas qhov muaj feem ua ntej. P-selectin yog cov cell adhesion protein uas ua lub luag haujlwm tseem ceeb hauv cov kev sib txuam ntau uas ua rau cov hlab ntshav txhaws.

Adakveo' s kev pom zoo rau kev lag luam cim lub sijhawm tshiab hauv kev kho SCD. Cov kab mob hlwb (SCD) yog hais txog ib pawg kab mob ntshav los ntawm noob ntshav liab, muaj npe tom qab cov ntshav liab yog" C" puab lossis" sickle" puab. Cov neeg mob SCD yog ib qho yooj yim nyuaj nrog vascular obstructive ntsoog (VOC), tshwj xeeb tshaj yog vascular obstructive ntsoog. Nov kuj yog lub laj thawj tseem ceeb rau cov neeg mob SCD mus nrhiav kev kho mob, tab sis tam sim no nws muaj cov kev pab cuam tsawg heev uas tuaj yeem tiv thaiv VOC. VOC raug cuam tshuam los ntawm cov kab mob sib xyaw ntawm ntau lub ntsej muag lossis cov xovtooj ntawm tes uas thaiv cov ntshav txaus, thiab cuam tshuam nrog cov kev muaj mob thiab ua kom tuag. Los ntawm hom phiaj P-selectin, Adakveo tuaj yeem txo qis multicellular adhesion.

CHMP cov kev xav tau zoo yog saib raws cov ntaub ntawv tau zoo los ntawm Ntu II SUSTAIN kev soj ntsuam kev kawm. Qhov no yog ntau lub chaw, ntau lub teb chaws, xaiv chaw, tswj chaw, ob lub qhov muag tsis pom kev, kawm 12 lub hlis kom ntsuas qhov ua tau zoo thiab kev nyab xeeb ntawm Adakveo ua ke nrog lossis tsis muaj kev kho hydroxyurea los tiv thaiv VOC hauv SCD cov neeg mob.

Cov txiaj ntsig tau pom tias piv nrog cov tshuaj placebo, Adakveo (5mg / kg) txo cov kev mob nruab nrab txhua xyoo ntawm VOC los ntawm 45.3% (1.63 vs 2.98, p=0.010) thaum ua ke nrog lossis tsis muaj kev kho hydroxyurea. Tsis hais txog ntawm SCD caj ces lossis kev siv hydroxyurea, qhov kev ntsuas mob tseem ceeb txo qis hauv VOC zaus tau pom. Tsis tas li ntawd, txoj kev tshawb fawb kuj tau qhia tias qhov kev faib ua feem ntawm cov neeg mob hauv pawg Adakveo (5 mg / kg) uas tsis tau ntsib VOC thaum kho mob yog ntau dua ob zaug ntawm cov pawg placebo (36% vs 17%, p=0.010), thiab cov uas muaj thawj VOC Lub sijhawm nyob yog peb zaug ntawm pawg placebo (4.07 hli vs 1.38 hli, p< 0.001),="" thiab="" cov="" tsev="" kho="" mob="" nruab="" nrab="" xyoo="" tau="" txo="" los="" ntawm="" 42%="" (4.00="" hnub="" vs="" 6.87="" hnub,="" p="">

Hauv kev hais txog kev nyab xeeb, qhov tshwm sim ntau tshaj plaws (tshwm sim ≥10%) hauv cov neeg mob kho nrog 5mg / kg Adakveo (n=111) suav nrog kev mob rov qab, xeev siab, kub cev thiab mob caj dab. Cov kev mob tshwm sim feem ntau yog mob sib khuav xwb (qib 1 lossis 2). Mob hnyav (Qeb 3) arthralgia thiab kub cev txhua 0.9% (1 kis). Raws li kev tshawb xyuas, tsis muaj cov neeg mob nres kho vim muaj kev phiv tshuaj. Hauv txoj kev tshawb nrhiav SUSTAIN, piv nrog cov pab pawg placebo, Adakveo pawg kho mob qhia tsis muaj kev nce ntau hauv kev kis tus kab mob tag nrho (53.0% vs 53.2%) lossis neutropenia (3.1% vs 6.5%) phiv kev tshwm sim.

VOC tseem tseem hu ua kev mob siab ntsws ntawm tes (SCPC), uas yog ib qho tsis tau paub thiab mob siab heev uas tuaj yeem ua rau muaj mob hnyav thiab mob hnyav hnyav tuag taus thiab tuag taus. VOC kuj tseem tuaj yeem ua rau muaj nuj nqis ntau ntawm kev kho mob. Nws yog qhov laj thawj feem ntau rau SCD cov neeg mob' mus ntsib chav khomob ceev thiab tsev khomob. Qhov nqi kho mob hauv nruab nrab rau ib tus neeg mob yog li 1 lab nyiaj daus las US, thiab tag nrho cov nqi kho mob txhua xyoo hauv Tebchaws Meskas tshaj li 1,1 billion lab daus las. Hauv cov neeg mob SCD, thaum ntau cov qe ntshav lo sib txuam thiab ua rau cov hlab ntshav, VOCs tuaj yeem tshwm sim, ua rau txhaws. Txo cov viscosity ntawm cov qe ntshav thiab cov hlab ntshav tuaj yeem pab txo qis cov hnub uas cov neeg mob tau ntsib VOC.

Cov tshuaj muaj tshuaj lom hauv Adakveo yog crizanlizumab, uas yog cov tshuaj tiv thaiv P-selectin monoclonal tiv thaiv kab mob uas tuaj yeem xaiv rau P-selectin nyob rau saum npoo ntawm endothelial hlwb thiab platelets hauv cov hlab ntshav, uas ua rau P-selectin thiab tiv thaiv endothelial cell Kev sib cuam tshuam ntawm platelets, qe ntshav liab, cov ntshav liab thiab cov qe ntshav dawb. P-selectin yog ib qho ntawm cov kev tsav tsheb tseem ceeb ntawm vascular occlusive ntsoog (VOC, ua rau vascular ob leeg), uas yog qhov muaj mob nyuaj rau ntawm SCD.

Tam sim no, Adakveo tab tom raug tsim los tiv thaiv VOC hauv SCD cov neeg mob. SUSTAIN yog ib feem ntawm SENTRY qhov kev tshawb fawb tshawb fawb, uas suav nrog ntau qhov kev tshawb fawb hauv chav kho mob kom tau txais cov ntaub ntawv txhua yam ntawm kev siv crizanlizumab hauv kev saib xyuas kho mob hauv SCD.