Lub EU CHMP Rov Pom Zoo Pom Zoo Kev Pom Zoo Ntawm Zejula (niraparib) Thawj-kab Kev Txij Nkawm Kho, tsis hais txog ntawm Biomarker, tau sau npe hauv Suav

Tsis ntev los no GlaxoSmithKline (GSK) tau tshaj tawm tias Lub Chaw Haujlwm Saib Xyuas Kev Noj Tshuaj hauv Tebchaws Europe (EMA) rau Cov Khoom Siv Tshuaj kho mob rau tib neeg (CHMP) tau tshaj tawm cov lus pom zoo hais qhia txog kev pom zoo ntawm lub hom phiaj tshuaj tua kab mob Zejula (niraparib) ua thawj kab kev saib xyuas kev siv tshuaj kho mob los kho cov neeg mob uas muaj mob qog qe ntshav siab heev uas teb rau platinum-muaj cov tshuaj kho mob, tsis hais txog lawv lub cev biomarker.

CHMP lub tswv yim yog ruam kawg ntawm kev lag luam tso cai ua ntej nws tau pom zoo los ntawm European Commission (EC). Tam sim no, CHMP cov tswv yim yuav muab xa mus rau EC rau qhov tshuaj xyuas, uas feem ntau lees txais CHMP cov lus pom thiab kev txiav txim siab zaum kawg li ntawm 2 hlis. Yog tias tau txais kev pom zoo, Zejula yuav dhau los ua EU' s thawj zaug-tus neeg sawv cev PARP inhibitor rau thawj kab kev saib xyuas kev kho mob hauv cov neeg mob uas muaj mob zes qe menyuam qib siab uas teb rau platinum-muaj tshuaj kho.

Thaum kawg lub Plaub Hlis xyoo no, Zejula tau pom zoo los ntawm Asmeskas FDA raws li kev saib xyuas kev kho mob tib yam rau kev mob qog qe menyuam (suav nrog mob qog nqaij hlav rau qe menyuam, mob qog rau lub raum, thiab mob qog nqaij hlav rau lub hlwb) uas tau ua tiav lossis ib feem ntawm kev zam thawj zaug- kab kab mob platinum-muaj tshuaj khomob Tus poj niam mob, tsis hais txog qhov xwm txheej biomarker. Qhov kev pom zoo no yog qhov kev nce qib loj hauv kev kho mob ntawm zes qe menyuam. Vim tias ua ntej ntawd, tsuas yog 20% ​​ntawm cov neeg mob qog nqaij hlav zes qe menyuam, uas yog, cov neeg mob BRCA hloov pauv (BRCAm), tau tsim nyog siv cov tshuaj PARP inhibitors li monotherapy hauv kev kho thawj zaug kev kho mob.

Cov ntaub ntawv soj ntsuam qhia tau tias nyob rau hauv tag nrho txoj kev tshawb fawb pej xeem (tsis hais txog qhov xwm txheej biomarker), BRCA kev hloov pauv ntawm cov neeg, homologous recombination kho mob (HRD zoo) BRCA cov pej xeem, thiab homologous recombination ib txwm muaj (HRD tsis zoo) cov pej xeem, piv nrog placebo, Zejula thawj-kab kev kho kev saib xyuas txo kev pheej hmoo ntawm tus mob lossis tuag tau 38%, 60%, 50%, thiab 32%, nyob ntawm.

Daim ntawv thov ntawm Zejula ua ib leeg-tus neeg sawv cev thawj kho kab mob kev kho mob rau kev mob qog qe menyuam yog ua raws cov txiaj ntsig ntawm Kev Tshawb Fawb III PRIMA (ENGOT-OV26 / GOG-3012). Hauv qhov kev tshawb nrhiav no, cov neeg muaj qib siab (theem III lossis IV) cov neeg mob uas tau txais kev zam txim tom qab tau txais thawj kab-muaj cov tshuaj tua kab mob plasma raug cia li raug xaiv kom tau txais Zejula lossis placebo kev kho mob ntawm 2: 1 piv. Thawj qhov kawg yog qhov kev vam meej-tsis muaj sia nyob (PFS). Cov Tib Neeg Zejula kho thaum xub thawj suav nrog kev tshawb fawb: cov neeg mob lub cev qhov hnyav< 77="" kg="" thiab="" lossis="" platelet="">< 150k="" μl,="" thawj="" qhov="" kev="" txhaj="" tshuaj="" yog="" 200="" mg="" ib="" hnub="" ib="" zaug;="" qhov="" pib="" siv="" rau="" lwm="" tus="" neeg="" mob="" yog="" 300="" mg="" ib="" hnub="" ib="">

Cov txiaj ntsig tau pom tias txoj kev tshawb no mus txog qhov kawg: nyob rau hauv tag nrho cov neeg mob kev kawm (tsis hais lub sijhawm biomarker), Zejula txo qis kev pheej hmoo ntawm kev mob lossis tuag los ntawm 38% piv nrog cov tshuaj placebo thaum siv thawj kev saib xyuas kev kho ( HR=0.62, 95% CI: 0.50-0.75, p< 0.001).="" ib="" qho="" tseem="" ceeb,="" ob="" qho="" tib="" si="" ntawm="" homologous="" recombination="" puas="" tsuaj="" (hrd="" zoo)="" thiab="" homologous="" recombination="" ib="" txwm="" muaj="" (hrd="" tsis="" zoo)="" qhia="" pom="" cov="" chaw="" muaj="" txiaj="" ntsig="" zoo="" thiab="" cov="" txiaj="" ntsig="" tseem="" ceeb.="" cov="" txiaj="" ntsig="" no="" tau="" tsav="" los="" ntawm="" kev="" txo="" qis="" kev="" pheej="" hmoo="" ntawm="" cov="" kab="" mob="" loj="" hauv="" kev="" kho="" mob:="" brca="" cov="" qog="" hlav="" (txo="" qhov="" phom="" sij="" 60%,="" hr="0.40," 95%="" ci:="" 0.27-0.62,="">< 0.001),="" homologous="" recombination="" tsis="" xws="" luag="" (hrd="" zoo="" )="" brca="" hom="" qog-hlav="" (50%="" kev="" pheej="" hmoo="" txo,="" hr="0.50" [95%="" ci:="" 0.30–0.83],="" p="0.006)," homogous="" recombination="" ib="" txwm="" muaj="" (hlav="" hrd="" tsis="" zoo)="" cov="" qog="" (yuav="" raug="" txo="" 32%,="" hr="0.68" [95%="" ci="0.49–0.94]," p="">

Hauv kev txheeb xyuas ib ntus ntawm tag nrho cov kev muaj sia nyob (OS), Zejula tseem qhia txog kev txhawb nqa ntawm kev txhim kho hauv OS piv nrog cov placebo. Kev soj ntsuam ua ntej OS cov kev ntsuam xyuas pom tias muaj txiaj ntsig rau Zejula hauv tag nrho cov kev kawm (HR 0.70; 95% CI: 0.44-1.11). Hauv HR tsis muaj pawg me, 91% ntawm cov neeg mob kho nrog Zejula muaj sia nyob 24 lub hlis ntawm kev kho, thiab 85% ntawm cov neeg mob kho nrog cov placebo (HR=0.61; 95% CI: 0.27-1.40). Cov ntaub ntawv no tseem tsis tau tiav, thiab lawv qhov tseem ceeb tseem tsis tau to taub tag nrho. Kev soj ntsuam ntawm OS nyob ib ntus kuj pom tias hauv pawg neeg tsawg nrog HR txaus, 81% ntawm cov neeg mob kho nrog Zejula muaj sia nyob 24 lub hlis ntawm kev kho mob, thiab 59% ntawm cov neeg mob kho nrog placebo (HR=0.51; 95% CI: 0.27-0.97).

Cov ntaub ntawv muaj kev nyab xeeb uas qhia hauv qhov kev kawm no yog qhov txawv txav tsis tau paub los ntawm kev paub txog kev nyab xeeb ntawm Zejula. Feem ntau qib 3 lossis siab dua cov kev phiv tshuaj nyob rau hauv Zejula suav nrog kuaj ntshav tsis txaus (31%), thrombocytopenia (29%), thiab neutropenia (13%). Kev siv ntawm kev noj tshuaj ib leeg ib leeg raws li qhov hnyav ntawm lub cev thiab / lossis cov ntshav platelet tuaj yeem txo qhov tshwm sim ntawm qhov tshwm sim tsis zoo (TEAE) hauv kev kho hematology. Tsis pom cov cim tshiab txog kev nyab xeeb. Cov txiaj ntsig ntawm kev ua tiav tus neeg mob qhia tau hais tias lub neej zoo hauv pab pawg kho mob Zejula thiab cov placebo pab pawg zoo sib xws.

Ntiaj teb, mob kheesxaws ntawm zes qe menyuam yog qhov yim mob loj tshaj plaws ua rau neeg tuag mob rau cov pojniam. Hauv Tebchaws Meskas thiab Tebchaws Europe, kwv yees li 22,000 thiab 65,000 tus pojniam tau kuaj pom tias muaj kabmob kheesxaws ntawm zes qe menyuam txhua xyoo. Txawm hais tias thawj-platinum-muaj cov tshuaj tua kab mob muaj cov lus teb tau zoo, kwv yees li ntawm 85% ntawm cov neeg mob yuav ntsib kev mob rov qab los. Thaum rov muaj mob, nws nyuaj kho, thiab lub sijhawm nyob nruab nrab ntawm txhua qhov kev rov tshwm sim yog luv.

Lub PRIMA txoj kev kawm sau npe cov neeg mob uas pom kev kho cov lus teb rau thawj kab-muaj cov tshuaj tua kab mob, nrog rau cov neeg muaj kev pheej hmoo siab mob ua mob. Qhov no yog cov pejxeem uas muaj kev xav tau kev pab kho mob siab thiab tsis muaj feem cuam hauv kev tshawb nrhiav kab mob cancer ntawm zes qe menyuam ua ntej dhau los. Txoj kev tshawb no yog qhov kev kawm txog av. Cov ntaub ntawv ua pov thawj qhov tseem ceeb ntawm Zejula' s thawj kab kev kho kev kho mob thiab nws cov txiaj ntsig kho mob rau cov poj niam uas muaj mob kheesxaws ntawm zes qe menyuam. Zejula ib leeg-tus neeg saib xyuas thawj kho kab mob kev kho mob tom qab kev phais thiab thawj-platinum-muaj tshuaj kho yuav muab cov neeg mob nrog txoj kev kho mob tseem ceeb tshiab, thiab nws yuav yog lub hauv paus rau kev kho mob ntawm zes qe menyuam.

Cov tshuaj kws tshaj tawm ntawm Zejula yog niraparib, uas yog lub qhov ncauj me me molecule poly ADP ribose polymerase (PARP) inhibitor uas tuaj yeem coj kom zoo dua ntawm cov tsis xws luag hauv DNA kho txoj hauv kev kom xav tau tua cov qog hlwb. Hom kev txiav txim siab no muab tshuaj kho mob Cov peev xwm rau ntau hom qog noj ntshav nrog DNA kho tsis xws luag. PARP muaj feem xyuam nrog ntau ntawm cov qog ntshav, tshwj xeeb yog mob cancer ntawm lub mis thiab zes qe menyuam. Zejula tau tsim los ntawm Tesaro, uas tau los ntawm GlaxoSmithKline thaum Lub Kaum Ob Hlis 2018 rau US $ 5.1 billion (kwv yees li billion 4 billion). Thaum lub Cuaj Hlis 2016, Zai Lab tau pom zoo daim ntawv tso cai pom zoo nrog Tesaro, tso cai ntawm Zejula ntawm Tuam Tshoj Mainland, Hong Kong, thiab Macau.

Zejula tau txais kev pom zoo rau kev lag luam thaum lub Peb Hlis 2017. Cov cim tau pom zoo tam sim no muaj xws li: (1) Rau kev saib xyuas cov neeg mob uas muaj cov kabmob kheesxaws ntawm lub zes qe menyuam, mob qog qe ntshav, lossis mob qog nqaij hlav peritoneal uas yog kiag lossis qee feem ntawm kev kho mob platinum-muaj tshuaj kho. (2) Siv rau kev mob kheesxaws zes qe menyuam tshaj plaws, mob qog qe ntshav los yog tub ntxhais peritoneum uas tau txais 3 lossis ntau dua kev kho mob hauv lub sijhawm yav dhau los thiab tus kabmob muaj feem cuam tshuam nrog cov xwm txheej zoo ntawm homologous recombination defect (HRD) tau hais tseg hauv ib qho ntawm 2 yam hauv qab no Kev kho mob rau cov neeg mob qog noj ntshav: (a) mob los yog xav tias tsam BRCA kev sib pauv; (b) genome tsis txaus ntseeg (GIS) thiab tus kab mob tau nce ntau dua 6 lub hlis tom qab teb rau platinum kawg muaj cov tshuaj kho mob.

Hauv Hong Kong thiab Macau, Tuam Tshoj, Zejula (niraparib) tau pom zoo rau cov npe thaum Lub Kaum Hli 2018 thiab Lub Rau Hli 2019. Hauv Suav teb av loj, National Medical Products Administration (NMPA) tau pom zoo Zejula (niraparib) rau lub Kaum Ob Hlis 27, 2019. Qhov tshuaj pom tias yog : rau kev rov ua dua mob epithelial ntawm zes qe menyuam mob thiab txoj hlab qe ntshav uas muaj tag nrho lossis ib nrab ntawm kev kho mob platinum-muaj tshuaj khomob Kev kho mob rau cov neeg laus uas muaj mob qog nqaij hlav lossis mob cancer peritoneal.