Tebchaws Asmeskas FDA pom zoo Ayvakit (avapritinib), KIT inhibitor, thiab CStone Pharmaceuticals qhia nws rau Tuam Tshoj!

CStone' tus koom tes Blueprint Medicines tsis ntev los no tshaj tawm tias Asmeskas Khoom Noj thiab Tshuaj Yeeb Tshuaj (FDA) tau pom zoo qhov kev qhia tshiab rau lub hom phiaj tshuaj tua kab mob qog noj ntshav Ayvakit (avapritinib) rau kev kho mob ntawm qib siab mastocytosis (SM) Cov neeg laus, suav nrog: txhoj puab heev SM (ASM), SM nrog cov qog hematological cuam tshuam (SM-AHN) thiab mast cell leukemia (MCL). Qhov kev qhia no tau pom zoo los ntawm txheej txheem tshuaj xyuas ua ntej. Yav dhau los, FDA tau tso cai Ayvakit Orphan Drug Designation (ODD) thiab Kev Tsim Tshuaj Yeeb Tshuaj (BTD) rau kev kho mob ntawm SM siab dua.

Nws yog qhov tsim nyog hais tias Ayvakit yog thawj qhov kev kho mob tau tsom mus rau lub hauv paus tseem ceeb ntawm kev mob SM. Kev pom zoo ntawm cov tshuaj ntawm kev ua lag luam muab rau cov neeg mob nrog qib siab SM thawj zaug rau kev kho mob. Ayvakit tuaj yeem muaj peev xwm thiab xaiv tau txwv D816V hloov pauv KIT, uas yog lub hauv paus tseem ceeb ntawm SM kab mob. Hais txog kev siv tshuaj, qhov tshuaj pom zoo ntawm Ayvakit rau cov neeg mob uas muaj mob SM siab tshaj yog 200 mg ib zaug ib hnub. Rau cov neeg mob uas muaj SM siab nrog cov platelet suav tsawg dua 50 X 10E9/L, Ayvakit tsis pom zoo.

SM yog kab mob ntshav tsawg thiab ua rau cov ntshav tsis txaus. Yuav luag txhua qhov xwm txheej tshwm sim los ntawm KIT D816V hloov pauv. Kev tswj tsis tau kev loj hlob thiab ua kom cov qog hlwb tuaj yeem ua rau muaj teeb meem rau txoj sia. Ntawm cov qib siab SM qib qis, qhov nruab nrab tag nrho kev muaj sia nyob (OS) ntawm ASM cov neeg mob yog li 3.5 xyoos, nruab nrab OS ntawm SM-AHN cov neeg mob yog kwv yees li 2 xyoos, thiab qhov nruab nrab OS ntawm MCL cov neeg mob tsawg dua 6 lub hlis. Ua ntej Ayvakit, tsis muaj kev pom zoo kho mob uas tuaj yeem xaiv qhov cuam tshuam KIT D816V hloov pauv. Multi-kinase inhibitor midostaurin tau pom zoo rau kev kho mob ntawm qib siab SM. Raws li IWG tus qauv, ORR yog 28%.

Ayvakit yog kev kho mob kom raug rau SM, thiab nws tsuas yog qhov muaj zog KIT D816V inhibitor uas tau ua pov thawj kho mob hauv SM. Cov ntaub ntawv muaj txiaj ntsig zoo thiab muaj kev nyab xeeb los ntawm ob qhov kev tshawb fawb tshawb fawb EXPLORER (NCT02561988) thiab PATHFINDER (NCT03580655) txhawb kev pom zoo tag nrho ntawm Ayvakit rau kev kho mob siab tshaj SM. Ob qho ntawm ob qhov kev sim no yog ntau qhov chaw, ib leeg-caj npab, qhib-daim ntawv lo sim. Tag nrho ntawm 53 tus neeg mob tau txais Ayvakit ib zaug kho ib hnub, suav nrog cov uas yav dhau los tau txais kev kho mob lossis tsis tau kho. Thawj qhov kawg yog qhov ntsuas tag nrho cov lus teb (ORR) thiab lub sijhawm teb (DOR) txiav txim siab raws li kev hloov kho IWG-MRT-ECNM cov qauv (IWG cov qauv).

Cov ntaub ntawv tau qhia tias ntawm txhua tus neeg ntsuas ntsuas (n=53) hauv 2 qhov kev sim, kev kho Ayvakit pom tias muaj cov lus teb zoo, nrog rau ORR ntawm 57% (95% CI: 42-70), ua tiav cov lus teb (CR) ntawm 28%, thiab ib nrab Qhov kev zam txim (PR) yog 28%. Ayvakit kev kho mob tau pom sai sai thiab zam txim ntev, nrog qhov nruab nrab DOR ntawm 38.3 lub hlis (95%CI: 19-NE), thiab lub sijhawm nruab nrab ntawm kev kho mob los teb rau 2.1 lub hlis. Qhov tshwm sim tsis zoo feem ntau (tshwm sim ≥20%) yog edema, raws plab, xeev siab, qaug zog/asthenia.

Thaum Lub Rau Hli 2018, CStone Pharmaceuticals tau mus txog qhov kev koom tes tshwj xeeb thiab daim ntawv tso cai pom zoo nrog Blueprint Medicines, thiab tau txais peb tus neeg sib tw tshuaj suav nrog avapritinib (muaj zog KIT/PDGFRA kinase inhibitor) thiabpralsetinib(lub zog RET inhibitor). Txoj cai kev txhim kho thiab kev lag luam hauv Suav teb (Mainland, Hong Kong, Macau, Taiwan).

avapritinibtuaj yeem xaiv thiab muaj zog tiv thaiv KIT thiab PDGFRA hloov pauv kinases. Cov tshuaj yog hom I inhibitor tsim los rau lub hom phiaj nquag kinase hloov pauv; tag nrho oncogenic kinases teeb liab los ntawm qhov kev hloov pauv no. Avapritinib tau pom tias muaj kev cuam tshuam dav dav ntawm GIST-cuam tshuam KIT thiab PDGFRA kev hloov pauv, suav nrog kev ua haujlwm muaj zog tiv thaiv kev ua kom lub voj hloov pauv ntsig txog kev tiv thaiv tam sim no kev kho mob. Piv nrog rau kev pom zoo ntau kinase inhibitors, avapritinib yog qhov xaiv ntau dua rau KIT thiab PDGFRA dua li lwm cov kinases. Ib qho ntxiv, avapritinib tau tsim tshwj xeeb los xaiv los khi thiab txwv tsis pub D816 hloov pauv KIT, uas yog tus kab mob sib kis nyob hauv kwv yees li 95% ntawm cov neeg mob uas muaj kab mob mastocytosis (SM). Preclinical cov kev tshawb fawb tau qhia tias avapritinib tuaj yeem tiv thaiv KIT D816V nrog lub zog nanomolar qis thiab muaj qhov ua haujlwm qis tshaj.

Hauv Tebchaws Meskas, European Union, thiab Tuam Tshoj,avapritinibtau pom zoo thaum Lub Ib Hlis 2020, Cuaj Hlis 2020, thiab Plaub Hlis 2021 (cov npe lag luam: Ayvakit, Ayvakyt, raws li) rau kev kho mob ntawm PDGFRA exon 18 hloov pauv (suav nrog PDGFRA D842V) Mutation) tsis tuaj yeem kuaj pom lossis mob plab zom mov hauv lub cev (GIST) hauv cov neeg laus. Nws tsim nyog hais tias Ayvakit yog thawj qhov kev kho mob tau pom zoo rau GIST thiab thawj cov tshuaj nrog kev ua haujlwm siab tiv thaiv GIST nrog kev hloov pauv hauv exon 18 ntawm PDGFRA noob.

Thaum lub Peb Hlis xyoo no,pralsetinibtau pom zoo los ntawm National Food and Drug Administration rau kev kho mob hauv zos lossis metastatic non-small cell lung cancer (NSCLC) cov neeg laus uas yav dhau los tau txais platinum-muaj tshuaj kho mob rau kev hloov pauv rov ua dua (RET) noob fusion zoo. Qhov no yog kev pom zoo ntawm Tuam Tshoj' thawj qhov kev xaiv RET inhibitor thiab tseem yog thawj qhov kev lag luam pib ntawm CStone Pharmaceuticals.