Roche Evrysdi (risdiplam) Tseem Ceeb Txhim Kho Lub Cev Muaj Zog&Ciaj sia nyob hauv Cov Me Nyuam Nrog Hom 1 SMA-1/2

Roche tsis ntev los no tshaj tawm tias kev tshuaj xyuas ntawm qhov ncauj tshuaj Evrysdi® (risdiplam) rau cov leeg txha nqaj qaum (SMA) thoob ntiaj teb theem 2/3 Kev kawm FIREFISH (NCT02913482) Ntu 2 cov ntaub ntawv tau tshaj tawm hauv phau ntawv xov xwm kho mob thoob ntiaj teb New England Journal of Medicine (NEJM). Saib: Risdiplam-Kho Cov Me Nyuam Nrog Hom 1 Spinal Muscular Atrophy tiv thaiv keeb kwm kev tswj hwm.

SMA yog thawj qhov caj ces ua rau tuag hauv cov menyuam mos thiab menyuam yaus, thiab 5q-SMA yog hom kab mob feem ntau. Tus kab mob no tuaj yeem ua rau cov leeg tsis muaj zog thiab ua rau lub cev tsis muaj zog ua haujlwm tau zoo, thiab muaj qhov xav tau kev kho mob tseem ceeb. Evrysdi tau pom zoo los ntawm Asmeskas FDA thaum Lub Yim Hli 2020 rau kev kho menyuam yaus thiab cov neeg laus nrog SMA ≥ 2 hli hnub nyoog. Thaum Lub Peb Hlis 2021, Evrysdi tau pom zoo los ntawm European Union los kho cov neeg mob nrog SMA ≥ 2 hli hnub nyoog thiab kuaj mob raws li hom 1/2 hom/3 SMA lossis 5q hom SMA nrog 1-4 daim qauv ntawm SMN2. Hauv Suav Teb, thaum Lub Rau Hli xyoo no, Evrysdi (Aimanxin®, Lisporan qhov ncauj hais daws hmoov) tau pom zoo los ntawm Lub Xeev Khoom Noj thiab Tshuaj rau kev kho mob SMA cov neeg mob hnub nyoog 2 hlis thiab laus dua. Raws li tam sim no, Evrysdi tau pom zoo hauv 54 lub tebchaws thiab tau xa daim ntawv thov kev lag luam hauv 33 lwm lub tebchaws.

Evrysdi yog thawj qhov kev kho lub qhov ncauj rau SMA thiab thawj txoj kev kho SMA uas tuaj yeem ua rau hauv tsev. Cov tshuaj yog kev npaj ua kua uas tuaj yeem tswj tau qhov ncauj lossis los ntawm lub raj pub mis hauv tsev, ib hnub ib zaug. Cov tshuaj tuaj yeem siv los kho menyuam yaus, menyuam yaus, tub ntxhais hluas, thiab cov neeg laus nrog txhua hom (hom 1, hom 2, thiab hom 3) ntawm SMA. Evrysdi yog lub cev muaj zog neuron muaj sia nyob noob caj noob ces 2 (SMN2) mRNA splicing modifier, uas kho SMA los ntawm kev tsim cov tshuab neuron muaj sia nyob muaj protein ntau (SMN). SMN cov protein tau faib thoob plaws lub cev thiab yog qhov tseem ceeb rau kev tswj kom muaj lub cev muaj zog lub paj hlwb thiab ua kom lub cev muaj zog.

Qhov thib ob ntawm FIREFISH txoj kev tshawb fawb tau ua hauv cov menyuam mos uas muaj cov tsos mob yam 1 SMA uas muaj hnub nyoog 1-7 hlis thaum lub sijhawm rau npe nkag. Cov txiaj ntsig tau pom tias txoj kev tshawb fawb mus txog qhov kawg qhov kawg: ntawm 12 lub hlis ntawm kev kho mob, 29% ntawm cov menyuam mos (12/41) zaum yam tsis muaj kev txhawb nqa tsawg kawg 5 vib nas this, qhov tseem ceeb uas tsis tau pom dua ib txwm muaj ntawm tus kabmob. Hauv ntu thib ob ntawm FIREFISH txoj kev kawm, kev nyab xeeb ntawm Evrysdi zoo ib yam nrog nws cov yam ntxwv paub txog kev nyab xeeb. Thaum Lub Ob Hlis 2021, 12-hli cov txiaj ntsig ntawm thawj koob tshuaj FIREFISH tau luam tawm ntawm NEJM.

FIREFISH tus kws tshawb fawb thiab MDUK Oxford Neuromuscular Center Professor ntawm Pediatric Neuromuscular Kab Mob, Laurent Servais, hais tias:" Yog tsis kho, menyuam mos uas muaj hom 1 SMA tsis tuaj yeem muaj sia nyob dhau 2 xyoos. Qhov tseem ceeb ntawm lub cev muaj zog ua tiav los ntawm kev kho Evrysdi, xws li zaum, Tig thiab nqos yog cov hauv paus los pab cov menyuam no ua tiav cov txiaj ntsig zoo tshaj plaws. Lawv muaj lub peev xwm los txo qhov xav tau kev tso pa tawm mus tas li thiab nce tus nqi kev ciaj sia."

Thaum lub sijhawm tshuaj xyuas cov ntaub ntawv, lub sijhawm nruab nrab ntawm Evrysdi kho yog 15.2 lub hlis, thiab hnub nyoog nruab nrab ntawm cov neeg mob yog 20.7 hli. Thaum lub hlis thib 12 ntawm kev kho mob, 93% (38/41) ntawm cov menyuam mos tau muaj txoj sia nyob, thiab 85% (35/41) ntawm cov menyuam mos tsis tau tso pa mus tas li. Tsis muaj kev kho mob, hnub nyoog nruab nrab ntawm kev tuag lossis tso pa tawm mus tas li hauv keeb kwm kab mob sib kis yog 13.5 hli. 90% (37/41) ntawm cov neeg mob tau nce tsawg kawg 4 cov qhab nia hauv CHOP-INTEND cov qhab nia, thiab 56% (23/41) tau qhab nia ntau dua 40 cov ntsiab lus, nrog qhov nruab nrab nce ntawm 20 cov ntsiab lus.

Ib qho ntxiv, txoj kev tshawb fawb tau mus txog ib qho ntawm cov ntsiab lus thib ob: 78% (32/41) ntawm cov neeg mob tau muab cais ua HINE-2 cov neeg teb. HINE-2 scale (Hammersmith Infant Neurological Examination Scale 2) ntsuas kev ua haujlwm ntawm lub cev los ntawm kev tswj lub taub hau, zaum ntawm lub cev, tuav tus kheej, ncaws, dov, nkag, sawv thiab taug kev muaj peev xwm. Yog tias ntau qhov kev tawm dag zog lub cev qhia pom kev txhim kho ntau dua li qhov phem zuj zus, tus menyuam mos tau muab cais ua HINE-2 cov lus teb.

Hauv ntu thib ob ntawm FIREFISH txoj kev kawm, kev nyab xeeb ntawm Evrysdi tau zoo ib yam nrog nws cov yam ntxwv paub txog kev nyab xeeb. Cov xwm txheej tsis zoo tshwm sim feem ntau yog kab mob ua pa ntawm lub ntsws (68%), mob ntsws (39%), kub cev (39%), cem quav (20%), raws plab (10%) thiab pob khaus maculopapular (10%). Cov xwm txheej tsis zoo feem ntau yog mob ntsws (32%), mob ntsws (5%), hypotonia (5%) thiab ua pa tsis ua haujlwm (5%). Peb tus menyuam mos tau tsim teeb meem tuag thaum thawj 3 lub hlis ntawm kev kho mob. Cov kws tshawb fawb ntseeg tias cov no tsis muaj dab tsi cuam tshuam nrog Evrysdi.

Thaum lub Plaub Hlis xyoo no, Roche tshaj tawm cov ntaub ntawv ob xyoos tshiab rau Tshooj 2 ntawm FIREFISH txoj kev tshawb fawb, uas pom tias Evrysdi txuas ntxiv txhim kho tus menyuam mos' lub cev muaj zog ua haujlwm, suav nrog kev muaj peev xwm zaum thiab sawv tsis muaj kev txhawb nqa, los ntawm 12 lub hlis txog 24 lub hlis. Kev tshawb fawb tseem qhia tau tias Evrysdi txuas ntxiv txhim kho cov neeg muaj sia nyob, txhim kho lub peev xwm pub mis hauv lub qhov ncauj, thiab txo qhov xav tau kev tso pa mus tas li. Cov ntaub ntawv tshawb fawb qhia pom tias piv nrog kev kawm ib txwm muaj ntawm hom 1 SMA, Evrysdi txuas ntxiv txhim kho kev nqos peev xwm thiab txo tus nqi pw hauv tsev kho mob. Evrysdi txoj kev nyab xeeb ua raws li nws tau teeb tsa kev nyab xeeb.