Scemblix Cov Ntaub Ntawv Tshiab: Kev Ua Tau Zoo Thiab Kev Nyab Xeeb Txuas Ntxiv Mus Ua Zoo dua Pfizer Bosulif (bosutinib)!

Novartis tsis ntev los no tau tshaj tawm ntawm 63rd Lub Rooj Sib Tham Txhua Xyoo ntawm American Society of Hematology (ASH2021) hauv 2021 cov ntaub ntawv tshiab 48-lub lim tiam ntawm cov tshuaj tiv thaiv kab mob tshiab Scemblix (asciminib, ABL001) Theem 3 ASCEMBL mus sib hais. Cov txiaj ntsig tau pom tias ntawm Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+CML-CP) cov neeg laus uas yav tas los tau txais tsawg kawg ob qhov kev kho mob tyrosine kinase inhibitors (TKI), Scemblix thiab Pfizer tsom cov tshuaj tiv thaiv kab mob piv nrog Bosulif. (bosutinib), qhov ua tau zoo thiab kev nyab xeeb zoo tshaj plaws nyob rau lub sijhawm ntawm kev tshuaj xyuas tseem ceeb (24 lub lis piam) yuav raug tswj xyuas ntxiv mus rau lub sijhawm ntev (48 lub lis piam).

Scemblix yog kinase inhibitor uas tau txais kev pom zoo nrawm los ntawm US FDA thaum Lub Kaum Hli 2021 rau kev kho mob ntawm Ph+CML-CP cov neeg laus uas yav tas los tau txais tsawg kawg yog ob qhov kev kho TKI. Scemblix yog STAMP inhibitor thiab thawj CML cov tshuaj kho mob uas tshwj xeeb tsom rau lub hnab tshos myristoyl (STAMP) ntawm BCR-ABL1 protein. Cov tshuaj sib tw tam sim no nyob rau hauv kev ua lag luam tau ua ke nrog ATP khi qhov chaw ntawm BCR-ABL1 protein.

Scemblix ua haujlwm los ntawm kev ua yeeb yam ntawm lwm qhov ntawm kinase, ABL myristoyl hnab tshos (STAMP), uas kaw BCR-ABL1 rau hauv qhov tsis sib haum xeeb. Yog li ntawd, Scemblix tuaj yeem pab daws qhov kev tawm tsam ntawm CML cov neeg mob rau TKI thiab kov yeej qhov tsis zoo BCR-ABL1 cov noob hloov pauv cuam tshuam nrog kev tsim tawm ntau dhau ntawm cov hlwb leukemia.

asciminib tshuaj qauv

Cov ntaub ntawv 48-lub lim tiam tso tawm ntawm ASH lub rooj sib tham tau pom tias MMR hauv pab pawg kho mob Scemblix tau ntau dua ob npaug piv nrog rau pawg kho Bosulif (29.3% vs 13.2%), thiab cov tshuaj tshem tawm vim yog cov xwm txheej tsis zoo yog ntau dua 3. lub sij hawm qis (7.1% vs 25%)). Cov ntaub ntawv luam tawm yav dhau los 24 lub lis piam tau pom tias piv nrog pawg kho Bosulif, MMR hauv pab pawg kho mob Scemblix yuav luag ob npaug (25.5% vs 13.2%; p=0.029), thiab cov tshuaj tshem tawm tus nqi los ntawm cov xwm txheej tsis zoo raug txo los ntawm ntau tshaj 3 zaug (7% vs. 25%).

Nyob rau hauv qhov kev ntsuam xyuas tshiab tshaj tawm ntawm lub rooj sib tham, cov lus teb kuj tshwm sim tau ntev, nrog 60 ntawm 62 tus neeg mob hauv pab pawg kho mob Scemblix tswj MMR ntawm qhov kev ntsuam xyuas zaum kawg. Scemblix tseem muab cov lus teb sib sib zog nqus molecular (MR) los ntawm MR4 thiab MR4.5. Tus nqi MR4 thiab MR4.5 tus nqi ntawm lub 48th lub lim tiam yog 10.8% thiab 7.6%, feem, thaum tus nqi MR4 thiab MR4.5 tus nqi hauv pawg Bosulf raws li Cov no yog 3.9% thiab 1.3%. Tsis tas li ntawd, cov kev faib ua feem ntawm cov neeg mob uas tau mus txog qib BCR-ABL1 [IS] ≤ 1% thaum lub sij hawm 48 lub lis piam yog siab dua nyob rau hauv pab pawg neeg kho mob Scemblix dua li hauv pab pawg kho Bosulif (50.8% vs 33.7%). BCR-ABL1 [IS] ≤1% yog qhov kev kwv yees ntawm qhov kev cia siab ntev ntev nyob rau hauv cov neeg mob no uas yav tas los tau txais ntau txoj cai.

Dr. Michael J. Mauro, kws kho mob hematologist thiab tus thawj coj ntawm qhov project qog myeloproliferative ntawm Memorial Sloan-Kettering Cancer Center (MSK), tau hais tias:" Peb feem ntau pom tias kev siv cov tshuaj TKI txuas ntxiv tuaj yeem ua rau qhov ua tsis tiav thiab raws li. cov neeg mob nkag mus rau kev kho mob siab heev, yuav muaj kev txhawj xeeb ntau dua txog kev kho mob tshwm sim. Scemblix muab qhov kev xaiv paub tab rau CML cov neeg mob uas tau sim ob lossis ntau dua TKIs, thiab cov tshuaj tau txais ib txoj hauv kev sib txawv los muab cov phiaj xwm inhibition kom tswj tau CML zoo dua."

Nyob rau hauv xyoo tas los no, kev kho mob ntawm CML tau ua tiav. Thaum kho Ph+CML cov neeg mob, cov kws kho mob tuaj yeem xaiv los ntawm ob peb TKIs, suav nrog Novartis's Gleevec (imatinib) thiab Tassigna (nilotinib). Cov neeg mob feem ntau tau txais kev kho mob tseem muaj sia nyob tom qab 10 xyoo, tab sis lawv tseem muaj kev pheej hmoo ntawm kev kis kab mob.

Txawm hais tias cov neeg mob uas tiv taus qhov kev kho mob thawj zaug tuaj yeem hloov mus rau lwm qhov TKI (piv txwv li, kev kho TKI txuas ntxiv), ntau cov kev kho mob pom zoo tsom rau tib qhov chaw sib txuas ATP ntawm ABL1 kinase. Qhov zoo sib xws ntawm cov kev kho mob no txhais tau hais tias kev hloov pauv hauv ib cheeb tsam ntawm kinase tuaj yeem ua rau ntau yam tshuaj tsis zoo. Hauv lwm lo lus, kev kho TKI txuas ntxiv tuaj yeem cuam tshuam nrog kev siv tshuaj ntau ntxiv thiab kev tsis haum tshuaj.

Raws li STAMP inhibitor, Scemblix tuaj yeem kov yeej kev hloov pauv hauv ATP khi qhov chaw ntawm BCR-ABL1, uas tuaj yeem pab daws TKI tsis kam nyob rau tom qab kev kho mob ntawm CML thiab tuaj yeem daws cov haujlwm tawm ntawm lub hom phiaj, yog li txhim kho cov kev mob tshwm sim ntawm cov neeg mob. Tsis tas li ntawd, US FDA tau tso caiasciminibFast Track Status (FTD). Thaum Lub Ob Hlis 2021, FDA tau tso cai rau asciminib 2 qhov kev tsim nyog tshuaj (BTD): (1) rau kev kho mob myelogenous leukemia uas yav tas los tau txais tsawg kawg 2 tyrosine kinase inhibitors (TKI) kev kho mob thiab Philadelphia chromosome-positive chronic myelogenous leukemia Phase ( Ph+CML-CP) cov neeg laus; (2) rau kev kho mob ntawm Ph+CML-CP cov neeg laus nrog T315I hloov pauv.

Tam sim no, Novartis tab tom ua ntau qhov kev sim tshuaj ntsuam xyuas Scemblix rau cov neeg mob CML uas tau txais ntau yam kev kho mob, nrog rau lwm yam TKIs rau kev kho mob ntawm cov neeg mob CML tshiab. Hauv lub rooj sib tham txog nyiaj khwv tau los peb lub hlis twg, Novartis tau tshaj tawm tias nws tau pib txoj kev tshawb fawb Scemblix thawj kab.