Bristol-Myers Squibb lub deucravacitinib hauv kev kho mob ntawm psoriasis 2 theem 3 kev soj ntsuam kev ua tau zoo tshaj li Amgen Otezla!

Bristol-Myers Squibb (BMS) tsis ntev los no tshaj tawm ntawm 2021 American Academy of Dermatology Virtual Conference Kev Sib Tham (AAD VMX) kev soj ntsuam ntawm cov tshuaj tiv thaiv kev kho mob tshiab deucravacitinib (BMS-986165) hauv kev kho mob ntawm cov neeg mob uas muaj mob loj rau cov quav hniav mob psoriasis. Cov txiaj ntsig zoo ntawm qhov tseem ceeb Theem 3 kawm (POETYK PSO-1, POETYK PSO-2). Deucravacitinib yog thawj-hauv-hauv qhov ncauj, qhov ncauj, xaiv tyrosine kinase 2 (TYK2) inhibitor nrog cov txheej txheem tshwj xeeb ntawm inhibiting IL-12, IL-23, thiab hom 1 interferon txoj hauv kev. Cov tshuaj no yog thawj zaug thiab tsuas yog TYK2 inhibitor yuav raug ntsuas hauv kev tshawb fawb hauv kev kho mob rau kev kho mob ntawm ntau yam kab mob tiv thaiv kab mob.

Cov txiaj ntsig tau tshaj tawm ntawm lub rooj sib tham pom tias ob txoj kev tshawb fawb tau mus txog qhov tseem ceeb tshaj plaws thiab qhov kawg ntawm qhov kawg: nws tau lees tias deucravacitinib (6 mg, ib zaug ib hnub) piv nrog cov placebo thiab Otezla (apremilast, 30 mg, ob zaug ib hnub) qhov ua tau zoo thiab kev ua kom tau zoo tshaj, suav nrog kev sib piv ntawm cov neeg mob ua tiav rau cheeb tsam mob psoriasis thiab qhov kev ua tau zoo ntawm qhov kev ntsuas qhov tsawg tshaj li 75% piv rau lub hauv paus (PASI75) piv rau cov placebo thiab Otezla nyob rau lub lim tiam 16, tus kws kho mob zoo li qub kev ntsuam xyuas (sPGA)) Cov qhab nia ua tiav lossis yuav luag tiav tshem tawm cov tawv nqaij tawv nqaij (sPGA 0/1). Piv nrog Otezla, qhov ntau dua ntawm cov neeg mob nce mus txog PASI75 thiab sPGA 0/1 nyob rau lub limtiam 24 thiab tswj kom txog rau lub limtiam 52. Hauv qhov kev tshawb fawb no, deucravacitinib muaj kev nyab xeeb thiab zoo.

Plaub Hlis Arm Armstrong, MD, tus kws tshaj lij ntawm cov tawv nqaij hauv University of Southern California, tau hais tias: "Hauv ob txoj kev tshawb nrhiav tseem ceeb no, deucravacitinib zoo dua Otezla nyob rau ntau qhov chaw kawg, suav nrog cov lus teb kom ruaj thiab tswj kev ntsuas. Qhov no qhia tau hais tias yuav tsum muaj kev kho mob rau lub cev, Xav tau cov kev xaiv lub qhov ncauj zoo dua los kho cov neeg mob uas muaj mob sib khuav rau cov quav hniav, kev kho tus mob deucravacitinib muaj lub peev xwm los ua tus qauv tshiab ntawm kev kho qhov ncauj. Vim tias ntau tus neeg mob uas muaj mob loj tsawv mus txog rau cov mob caj dab los tseem tsis tau txais kev kho kom tsim nyog, lossis txawm tias tsis muaj kev kho mob, yog li nws tseem tau txhawb tias deucravacitinib txhim kho cov tsos mob ntawm tus neeg mob thiab paub txog qhov ntau dua li Otezla."

Mary Beth Harler, MD, Lub taub hau ntawm Immunology thiab Fibrosis Development ntawm Bristol-Myers Squibb, tau hais tias: "Cov txiaj ntsig ntawm ob txoj kev tshawb fawb tau lees tias deucravacitinib muaj peev xwm dhau los ua qhov kev xaiv kev kho mob rau cov neeg mob psoriasis. Peb ntseeg hais tias deucravacitinib yog qhov muaj ntau yam kabmob ntawm kev tiv thaiv kab mob. Nrog lub peev xwm loj, peb tau cog lus rau kev nce qib ntau qhov kev txhim kho kev kho mob ntawm deucravacitinib. Tam sim no, peb tab tom tham nrog cov chaw tswj hwm txoj cai nrog lub hom phiaj ntawm kev coj txoj kev kho tshiab no rau cov neeg mob uas tsim nyog kom sai li sai tau."

Otezla yog qhov ncauj tawm tsam kev tiv thaiv tshuaj ntawm Celgene, uas tau los ntawm Amgen rau Asmeskas $ 13.4 nphom hauv lub Yim Hli 2019. Lub Ib Hlis 2019, Bristol-Myers Squibb (BMS) tau tshaj tawm qhov yuav los ntawm New Base rau US $ 74 nphom. Raws li ib feem ntawm US Federal Trade Commission' s (FTC) tshuaj xyuas kev tiv thaiv, Otezla raug yuam kom muag thiab Amgen coj. Otezla yog qhov ncauj xaiv phosphodiesterase 4 (PDE4) cov tshuaj tua kab mob me me thiab tau pom zoo rau 3 qhov kev qhia (mob hnyav rau cov quav hniav liab, dhia ua mob psoriatic, Kab mob ntsig txog lub qhov ncauj ua rau mob). Lub sijhawm, Otezla tsuas yog kho qhov ncauj, tsis muaj tshuaj lom neeg rau psoriasis thiab mob caj dab, thiab tsuas yog cov tshuaj los kho Behcet kab mob ntsig txog qhov ncauj. Raws li daim ntawv qhia ua haujlwm xyoo 2020 tso tawm los ntawm Amgen, Otezla tau muag nyiaj ntawm Asmeskas $ 2.195 billion, ua rau nws yog qhov tshuaj thib 3 zoo tshaj plaws rau Amgen.

Deucravacitinib yog qhov ncauj tshiab xaiv hom TYK2 inhibitor tsim los ntawm Bristol-Myers Squibb. Nws muaj qhov tshwj xeeb mechanism ntawm kev ua txawv ntawm lwm cov kinase inhibitors. TYK2 yog qhov teeb meem kibase khes mis rau nruab nrab uas daws cov teeb meem sib kis ntawm IL-23, IL-12, thiab hom I IFN. Cov cytokines no yog ntuj cytokines koom nrog rau kev mob thiab tiv thaiv kab mob hauv lub cev. EvaluatePharma, lub koom haum tshawb fawb kev lag luam tshuaj, tau tshaj tawm ib daim ntawv qhia thaum pib ntawm lub xyoo no kwv yees tias kev muag khoom deucravacitinib xyoo 2026 yuav ncav cuag 2.21 billion Asmeskas las.

Tam sim no, deucravacitinib tab tom raug soj ntsuam rau kev kho mob ntawm ntau cov kab mob hauv lub cev tiv thaiv kab mob, nrog rau psoriasis, mob caj dab, mob caj pas, mob caj pas thiab mob plab hnyuv. Ntxiv nrog rau POETYK PSO-1 thiab POETYK PSO-2, Bristol-Myers Squibb tseem tab tom ua peb lwm ntu 3 kev tshawb fawb ntawm deucravacitinib: POETYK PSO-3 (NCT04167462), POETYK PSO-4 (NCT03924427), POETYK PSO-34 )).

Tus qauv tshuaj lom neeg ntawm deucravacitinib (duab los ntawm: genome.jp)

POETYK PSO-1 (NCT03624127) thiab POETYK PSO-2 (NCT03611751) yog ob qho kev tshawb fawb thoob ntiaj teb 3 ua nyob rau hauv cov neeg mob uas muaj mob plua plav uas tsis mob hnyav txhawm rau txhawm rau txheeb xyuas qhov txheeb xyuas kom muaj kev nyab xeeb thiab muaj txiaj ntsig ntawm cov tshuaj placebo thiab Otezla (apremilast). Ob txoj kev tshawb no muaj ntau lub chaw, muaj kev xaiv, ob lub qhov muag dig, kev tso npe 666 thiab 1,020 tus neeg mob, ntsig txog, thiab tshuaj xyuas deucravacitinib (6 mg, ib hnub ib zaug), cov placebo thiab Otezla (30 mg, ob zaug ib hnub). POETYK PSO-2 kev tshawb fawb kuj tseem muaj lub sijhawm rho tawm thiab tshem tawm lub sijhawm tom qab 24 lub lis piam.

Qhov pom tseeb ntawm qhov xaus ntawm ob txoj kev tshawb fawb yog: ntawm 16 lub lim tiam ntawm kev kho mob, piv nrog cov pab pawg placebo, qhov sib piv ntawm cov neeg mob deucravacitinib kho pab pawg tau mus txog PASI75 thiab sPGA 0/1. Cov ntsiab lus tseem ceeb theem ob ntxiv suav nrog: hauv lub asthiv 16, qhov sib piv ntawm cov neeg mob uas ua tiav PASI75 thiab sPGA 0/1 hauv pawg kho mob deucravacitinib piv nrog Otezla kho pab pawg, thiab lwm yam ntsuas.

Cov txiaj ntsig pom tau hais tias ob qho kev tshawb fawb tau mus txog qhov tseem ceeb tshaj plaws: thaum 16 lub lim tiam ntawm kev kho mob, piv nrog cov pab pawg placebo, qhov feem pua ​​ntawm cov neeg mob ntau dua nyob hauv pawg kho mob deucravacitinib tiav PASI75 thiab sPGA 0/1. Hauv ob txoj kev tshawb nrhiav, lub sijhawm tseem ceeb Hauv nqe lus ntawm cov xaus, PASI75 thiab sPGA 0/1 ntawm 16 thiab 24 lub lis piam tau siv rau kev ntsuas. Deucravacitinib pom tias muaj cov tawv nqaij ua kom huv zoo dua li Otezla. Deucravacitinib zoo zam lub siab, thiab tus nqi tsis tiav vim qhov xwm txheej tsis zoo (AE) yog tsawg.

Cov ntaub ntawv soj ntsuam Deucravacitinib

Cov kev tshwm sim yog:

——PASI75 cov lus teb hauv POETYK PSO-1 thiab POETYK PSO-2 cov kev tshawb fawb: (1) Lub lim tiam 16, 58.7% thiab 53.6% ntawm cov neeg mob hauv pawg kho mob deucravacitinib ua tiav PASI75 cov lus teb, thiab 12.7% hauv cov placebo pawg , raws li. 9.4% thiab Otezla pawg kho mob yog 35.1% thiab 40.2%, feem. (2) Lub sijhawm 24 lub lim tiam, 69.0% thiab 59.3% ntawm cov neeg mob hauv pawg kho mob deucravacitinib ua tiav PASI75 cov lus teb, thiab 38.1% thiab 37.8% hauv Otezla kho pawg, feem. (3) 82.5% thiab 81.4% ntawm cov neeg mob uas tau txais kev kho mob deucravacitinib mus txog PASI75 lus teb lub limtiam 24 thiab txuas ntxiv tau txais kev kho mob deucravacitinib, ntsig txog, tswj PASI75 lus teb hauv lub limtiam 52.

—— Cov sPGA 0/1 cov lus teb hauv POETYK PSO-1 thiab POETYK PSO-2 cov kev tshawb fawb: (1) Lub lim tiam 16, 53.6% thiab 50.3% ntawm deucravacitinib pawg kho mob tau ua tiav sPGA 0/1 cov lus teb, cov placebo Pawg yog 7.2 %, 8.6%, Cov pab pawg kho mob Otezla yog 32.1%, 34.3%. (2) Lub lim tiam 24, 58.4% thiab 50.4% ntawm cov neeg mob hauv pawg kho mob deucavacitinib ua tiav sPGA 0/1 teb, feem, thiab 31.0% thiab 29.5% hauv pab pawg kho mob Otezla, feem.

-Deucravacitinib tau qhia tias muaj peev xwm ua tau zoo piv nrog cov placebo thiab Otezla: suav nrog kev zoo dua rau cov placebo nyob rau hauv cov thawj qhov chaw kawg, thiab zoo dua rau Otezla hauv qhov tseem ceeb theem kawg. Ntxiv rau PASI75 thiab sPGA 0/1 ntsuas, deucravacitinib tau zoo dua Otezla nyob rau ntau qhov chaw xaus ntawm ob txoj kev tshawb fawb, qhia txog qhov tseem ceeb thiab chaw kuaj mob txhim kho cov tsos mob ntawm lub nra ntawm cov tsos mob thiab lub neej zoo.

——Safety thiab tolerability: Hauv 2 kev tshawb fawb, deucravacitinib muaj kev nyab xeeb thiab zoo rau. Tom qab 16 lub lis piam ntawm kev kho mob, 2.9% ntawm cov placebo pawg (n=419), 1.8% ntawm deucravacitinib pawg (n=842), thiab 1.2% ntawm Otezla pawg (n=422) tau ntsib qhov tsis zoo tshwm sim (SAE), ntsig txog 3.8%, 2.4% thiab 5.2% ntawm cov neeg mob tau ntsib cov xwm txheej tsis zoo (AE) uas ua rau cuam tshuam ntawm cov tshuaj. Tom qab 52 lub lim piam ntawm kev kho mob, SAE tom qab kis tus mob (qhov kev hloov kho tshwm sim rau tus neeg mob 100 xyoo [EAIR]) yog 5.7 hauv pawg placebo, 5.7 hauv pawg deucravacitinib, thiab 4.0 hauv pawg Otezla. Lub sijhawm tib lub sijhawm ntawm ob txoj kev tshawb nrhiav, EAIR uas ua rau kev txiav tawm ntawm cov tshuaj yog 9.4 nyob rau hauv cov pawg placebo, 4.4 nyob rau hauv pawg deucravacitinib, thiab 11.6 hauv Otezla pawg. Tsis muaj lub cim qhia txog kev nyab xeeb tshiab hauv lub lim tiam 16-52. Hauv ob txoj kev tshawb nrhiav, qhov tshwm sim ntawm cov qog ua hlav, cov kev mob plawv loj (MACE), cov leeg ntshav muaj zog (VTE), thiab cov mob hnyav tau tsawg, thiab lawv yog cov zoo ib yam hauv pawg kho mob nquag. Tsis pub dhau 52 lub lis piam, tsis muaj kev hloov pauv loj hauv cov chaw kuaj mob (suav nrog ntshav tsis txaus, ntshav hauv ntshav, lipids thiab daim siab ua siab).