Tsoom Fwv Teb Chaws Asmeskas FDA Pom Zoo Onureg: Thawj AML Txuas Ntxiv Kho Rau Tus Neeg Mob Nrog Kev Kho Mob Tag

Bristol-Myers Squibb (BMS) tsis ntev los no tshaj tawm tias Tsoomfwv Meskas Khoom Noj thiab Tshuaj (FDA) tau pom zoo Onureg (Azacitidine 300mg ntsiav tshuaj, CC-486), txoj kev kho qhov ncauj tshiab rau thawj zaug txuas ntxiv kev kho mob rau cov neeg mob laus uas muaj kev kho tau tus mob myeloid. leukemia (AML), tshwj xeeb: rau kev tau txais kev kho mob siab kom tau txais kev kho kom zoo thawj zaug (CR) lossis kev kho kom tiav (CRi) nrog kev ua tsis tiav cov ntshav ntawm cov ntshav suav, thiab tsis tuaj yeem ua tiav txoj kev kho kom zoo. Kev phais mob zoo (xws li hematopoietic qia cell hloov ntshav). AML yog ib qho kev mob ntsws hnyav tshaj plaws rau cov neeg laus.

Nws tsim nyog teev tias Onureg yog thawj zaug thiab tsuas kho txuas ntxiv rau AML tau pom zoo los ntawm FDA rau cov neeg mob hauv kev zam txim. Onureg tau pom zoo los ntawm kev txheeb xyuas txheej txheem ua ntej. Tam sim no, daim ntawv thov tso cai muag lag luam (MAA) rau cov tshuaj rau tib qho kev ntsuas tseem tab tom kuaj xyuas los ntawm European Medicines Agency (EMA). Hais txog kev siv tshuaj, Onureg tuaj yeem txuas ntxiv mus kom txog thaum tus mob loj zuj zus lossis tsis tuaj yeem tsis tuaj yeem lom. Vim tias qhov sib txawv tseem ceeb hauv cov chaw muag tshuaj tsis haum, Onureg yuav tsum tsis txhob hloov cov leeg mob los yog subcutaneous azacitidine.

Onureg' s cov tshuaj kws tshaj tawm yog CC-486 (Azacitidine), tus neeg sawv cev ntawm lub qhov ncauj hypomethylation uas khi rau DNA thiab RNA, tso cai rau cov kev cai epigenetic txuas ntxiv vim yog raug lub sijhawm ntev. Tam sim no, cov tshuaj tau raug tsim los ntawm kev hloov kho epigenetic rau kev kho mob ntawm ntau cov qog hematological. Lub tshuab tseem ceeb ntawm cov tshuaj' s kev ua haujlwm yog xav tias yog DNA hypomethylation thiab cytotoxicity ncaj qha rau cov ntshav tsis txaus hematopoietic hauv cov leeg pob txha. Hypomethylation tuaj yeem txum rov qab lub luag haujlwm ntawm cov noob tseem ceeb rau kev sib txawv thiab loj hlob.

Azacitidine tshuaj qauv

AML yog hom kev sib deev ntxim nyiam kawg. AML pib rau hauv cov leeg pob txha, tab sis nkag mus rau hauv cov hlab ntshav. Tsis zoo li txoj kev loj hlob ntawm cov ntshav dawb, hauv AML, kev nce ceev ceev ntawm cov qe ntshav dawb nyob rau hauv cov hlwb pob txha yuav cuam tshuam nrog kev tsim cov qe ntshav li qub, uas ua rau cov ntshav dawb tsis muaj ntshav, ntshav liab, thiab qe ntshav. AML yog ib yam kab mob nyuaj thiab muaj ntau yam, uas muaj feem xyuam rau ntau yam noob caj noob ces. Yog tias tsis kho, tus mob feem ntau yuav sai sai.

Cov neeg laus uas muaj tus mob AML tshiab feem ntau tuaj yeem ua tiav kev kho kom tiav los ntawm kev siv tshuaj kho mob induction, tab sis ntau tus neeg mob yuav rov qab los thiab ntsib cov txiaj ntsig tsis zoo. Cov neeg mob uas tau txais kev pab kom maj nrawm xav tau lub phiaj xwm kho mob uas tuaj yeem txo qhov kev pheej hmoo rov qab thiab yuav tag nrho kev ua neej nyob ntev. Kev pom zoo ntawm Onureg rau kev tshaj tawm yuav daws cov kev kho mob maj nrawm ntawm cov neeg mob AML rau cov kev kho tshiab cov kev xaiv kho.

Qhov kev pom zoo no yog ua raws li kev ua tau zoo thiab kev nyab xeeb ntawm kev ntsuas tus qauv Phase III QUAZAR AML-001 kawm. Txoj kev tshawb no tau ua nyob rau hauv cov neeg nyuam qhuav raug mob tshiab ntawm AML uas tau txais kev kho mob siv tshuaj thiab lawv cov mob tau kho, thiab tau tshuaj xyuas kev ua tau zoo thiab kev nyab xeeb ntawm Onureg ua thawj kab kev saib xyuas kev kho mob. Cov txiaj ntsig pom tau hais tias piv nrog cov placebo, Onureg pom zoo tag nrho cov kev ua neej nyob (OS, thawj qhov kawg) los ze li 10 lub hlis nyob rau thawj kab kev saib xyuas kev kho mob (nruab nrab OS: 24.7 lub hlis vs 14.8 lub hlis, p=0.0009), tsis muaj kev rov muaj sia (RFS, qhov tseem ceeb theem nrab qhov xaus) tau nce ntau dua ntau dua ob npaug (nruab nrab PFS: 10.2 lub hlis vs 4.8 hli, p=0.0001), thiab cov txiaj ntsig tau zoo dua qub thiab cov chaw kuaj mob txhim kho tseem ceeb.

Tus kws tshawb fawb soj ntsuam ntawm QUAZAR AML-001, Tsev Kho Mob Alfred hauv Melbourne, Australia thiab Dr. Andrew Wei ntawm Monash University tau hais tias:" Hauv cov neeg mob AML uas tau ua tiav kev zam thawj zaug hauv QUAZAR AML-001 kawm, Onureg txuas ntxiv kev kho mob qhia tag nrho cov nyiaj pab kev ciaj sia. Hauv kev tshwj xeeb, muab nws ib zaug ib hnub-qhov ncauj tsim, cov tshuaj muaj peev xwm ua tiav qhov no nyob hauv txoj kev yooj yim. Kev pom zoo no yuav pab tsim kho kev kho mob tas mus li nrog Onureg ua tus txheej txheem ntawm AML kev kho mob thawj zaug tom qab cov tshuaj tua kab mob rau cov neeg mob loj ntawm cov neeg mob AML uas tau txais kev kho kom tiav thiab tsis tuaj yeem siv cov tshuaj kho mob ntau ntxiv xws li hematopoietic qia cell hloov ntshav."

Dr. Giovanni Caforio, Tus Thawj Coj thiab Tus Thawj Coj ntawm Bristol-Myers Squibb tau hais tias:" FDA' kev pom zoo ntawm Onureg yog qhov tshwm sim ntau dua kaum xyoo ntawm kev tshawb nrhiav thiab 13 preclinical thiab kuaj mob. Peb ua tsaug rau cov neeg mob, cov tsev neeg thiab cov neeg saib xyuas uas tau koom nrog thiab txhawb nqa cov kev sim no. Tib neeg, lawv thaum kawg ua rau kev nce qib niaj hnub no muaj peev xwm. Cov keeb kwm no sawv cev rau peb kev cog lus los pab cov neeg mob qog nqaij hlav ntshav muaj sia nyob ntev dua, thiab nrog rau COVID-19 kis thoob plaws, kev pom zoo ntawm Onureg ua qhov ncauj kho rau cov neeg mob yog qhov tseem ceeb dua."

QUAZAR AML-001 yog txoj kev kawm thoob ntiaj teb, kev xaiv chaw, ob chav dig muag, kev kawm tshuaj placebo Ntu III kawm. Cov neeg mob uas muaj hnub nyoog muaj hnub nyoog years 55 xyoos, de novo lossis qib mob myeloid kab mob siab, mob ntshav nruab nrab lossis ntshav siab cytogenetics, thawj zaug ua tiav (CR) lossis kev kho tag nrho nrog cov ntshav tsis txaus rov qab (CRi) tom qab kev siv tshuaj kho mob siab. Nyob ntawm tus neeg tshawb xyuas' s kev xaiv, tus neeg mob tau txais kev kho mob siv tshuaj ntau, nrog lossis tsis muaj kev sib zog ntawm kev kho cov tshuaj, thiab tau raug txiav txim siab tsis yog tus neeg sib tw rau hematopoietic qia cell hloov chaw (HSCT) ua ntej pib kev kawm.

Tom qab siv tshuaj tua kab mob ntau dua, 81% ntawm cov neeg mob ua tiav CR, thiab 19% ntawm cov neeg mob ua tiav CRi. 80% ntawm cov neeg mob tau txais tsawg kawg ib lub voj voog los ntawm kev kho ua ke ua ntej koom nrog txoj kev tshawb fawb. 472 cov neeg mob tau muab faib ua ob pab pawg ntawm qhov sib piv ntawm 1: 1, thiab tau txais: Onureg 300 mg kho mob (n=238), tshuaj placebo (n=234), ib hnub ib zaug, txhua lub voj voog ntawm kev kho mob rau 14 hnub, txhua 28 Hnub yog lub voj voog. Hauv kev kawm, cov neeg mob tseem tau txais kev kho kom txog thaum tsis siv tshuaj lom lossis mob tshwm sim.

Nrog cov tshuaj nruab nrab soj qab taug qab ntawm 41,2 lub hlis, Pab pawg kho mob Onureg pom tias muaj kev txhim kho tseem ceeb hauv thawj qhov xaus ntawm OS piv nrog cov pab pawg placebo. Qhov nruab nrab OS los ntawm lub sijhawm randomization nyob rau hauv Pab pawg kho mob Onureg yog 24.7 hlis, thaum uas nyob hauv cov pab pawg placebo yog 14.8 lub hlis (p=0.0009; HR=0.69 [95% CI: 0.55, 0. 86]) Cov. Hais txog qhov tseem ceeb tshaj plaws kev xaus RFS, nruab nrab RFS yog 10.2 lub hlis nyob rau hauv Pab pawg kho mob Onureg thiab 4.8 hli nyob rau hauv cov tshuaj placebo (p=0.0001; HR=0.65 [95% CI: 0.52, 0.81]). Tsis hais txog qhov kev pheej hmoo cytogenetic, kev sib koom ua ke dhau los, lossis CR / CRi xwm txheej thaum lub sijhawm sau npe, OS thiab RFS hauv Onureg kev kho mob pab pawg zoo dua piv nrog cov pab pawg placebo. Piv nrog rau cov pab pawg placebo, cov kev noj qab haus huv muaj txiaj ntsig zoo nyob rau hauv lub neej (HRQoL) hauv pab pawg kho mob Onureg tseem tsis hloov pauv ntawm qhov pib.

Onureg' s kev kho mob hauv nruab nrab yog 12 mus (1-80), thiab cov placebo yog 6 mus (1-73). Cov xwm txheej tshwm sim tsis zoo (AEs) hauv txhua qib ntawm Onureg thiab placebo yog xeev siab (65% vs 24%), ntuav (60% vs 10%), thiab raws plab (50% vs 22%). Feem ntau qib 3-4 qhov xwm txheej tshwm sim rau CC-486 thiab cov placebo yog neutropenia (41% vs 24%), thrombocytopenia (23% vs 22%), thiab ntshav tsis txaus (14% vs 13%). 34% thiab 25% ntawm cov neeg mob hauv Pab pawg kho mob Onureg thiab cov placebo pawg muaj cov kev mob tshwm sim hnyav, feem ntau kis tau tus mob, uas tau tshwm sim hauv 17% thiab 8% ntawm cov neeg mob hauv ob pawg, feem. 13% thiab 4% ntawm cov neeg mob hauv Pab pawg kho mob Onureg thiab cov placebo pawg nres kev kho vim yog AEs.