Fintepla (fenfluramine) tau thov rau qhov qhia tshiab hauv Tebchaws Meskas thiab Europe: kev kho mob Lennox-Gastaut syndrome!

Zogenix yog lub tuam txhab kws tshuaj mob siab rau tsim kho cov kab mob tsawg. Tsis ntev los no, lub tuam txhab tau tshaj tawm tias nws tau xa Daim Ntawv Thov Kev Hloov Kho Qib II mus rau European Tshuaj Lub Chaw Haujlwm (EMA) rau Fintepla (fenfluramine) qhov ncauj tshuaj rau kev kho mob qaug dab peg cuam tshuam nrog Lennox-Gastaut syndrome (LGS), qhov siab heev. tshuaj- tiv thaiv menyuam yaus- pib mob qaug dab peg. Yog tias pom zoo, daim ntawv thov yuav nthuav dav siv Fintepla hauv Tebchaws Europe los kho LGS.

Thaum Lub Kaum Ib Hlis 2021, US Food and Drug Administration (FDA) tau lees txais thiab tso cai Kev Tshawb Fawb Tseem Ceeb rau Fintepla's supplemental New Drug Application (sNDA): rau kev kho mob qaug dab peg nrog LGS.

Hauv Teb Chaws Asmeskas thiab EU, Fintepla tau pom zoo nyob rau lub Rau Hli thiab Kaum Ob Hlis 2020 rau kev kho mob qaug dab peg nrog Dravet syndrome (DS) hauv cov neeg mob siab dua lossis sib npaug rau 2 xyoos. Fintepla yav dhau los tau tso cai Breakthrough Drug Designation (BTD) los ntawm US FDA rau kev kho mob ntawm LGS thiab DS.

LGS thiab DS yog ob qho tib si tsis tshua muaj thiab feem ntau muaj kev puas tsuaj rau menyuam yaus- pib mob qaug dab peg tshwm sim los ntawm cov hnub nyoog ntxov ntawm qhov pib, muaj ntau hom qaug dab peg, qaug dab peg ntau zaus, kev puas hlwb loj, thiab nyuaj rau kev kho mob.

Fintepla, ib tug kua formulation ntawm tsawg- koob tshuaj fenfluramine, txo qaug dab peg ntau zaus los ntawm modulating serotonin receptor thiab sigma-1 receptor kev ua (saib: Fenfluramine diminishes NMDA receptor-mediated qaug dab peg los ntawm nws cov kev ua si sib xyaw ntawm serotonin 5HT2A thiab hom 1 sigma receptors).

LGS yog ib hom mob qaug dab peg uas tsis tshua muaj thiab hnyav nrog kev kho mob siab thiab qaug dab peg nyob rau hauv yuav luag txhua tus neeg mob. Yog li ntawd, nquag ntog thiab raug mob, nrog rau kev paub tsis meej, txwv tsis pub lub neej zoo ntawm cov neeg mob thiab cov neeg saib xyuas, txawm tias nyob rau hauv cov kev kho mob tam sim no. Cov txiaj ntsig tau los ntawm cov placebo- tswj Phase 3 Txoj Kev Kawm 1601 txoj kev tshawb fawb pom tau tias kev kho mob nrog Fintepla txo qis qaug dab peg ntau zaus (piv txwv li qhov kawg) thiab ntog (qhov tseem ceeb thib ob qhov kawg) nrog rau kev nyab xeeb thiab kev tiv thaiv zoo. Yog tias pom zoo, Fintepla tuaj yeem muab cov neeg mob no thiab cov tsev neeg xav tau kev kho mob tshiab tseem ceeb.

Fenfluramine - Molecular Structural Formula (Duab Source: Wikipedia.org)

Daim ntawv thov qhia tshiab rau Fintepla rau kev kho mob ntawm LGS{{0}} ntsig txog qaug dab peg, raws li cov ntaub ntawv los ntawm Txoj Kev Kawm 1601 txoj kev tshawb fawb. Qhov no yog ntau qhov chaw thoob ntiaj teb LGS sim nrog 2 qhov chaw: Thawj ntu yog ob npaug - dig muag, placebo- tswj kev tshawb fawb soj ntsuam kev nyab xeeb, kev ua siab ntev thiab kev ua tau zoo ntawm Fintepla ntxiv rau cov neeg mob cov tshuaj tiv thaiv kab mob tam sim no. Txoj kev tshawb no tau tso npe rau 263 tus neeg mob, hnub nyoog 2-35, uas nws tus kab mob tswj tsis tau txawm tias kho nrog ib lossis ntau dua cov tshuaj antiepileptic (AEDs). Hauv txoj kev tshawb no, cov neeg mob tau muab faib ua peb pawg: Fintepla (0.7 mg / kg / hnub, qhov siab tshaj plaws txhua hnub ntawm 26 mg; n{10}}), Fintepla (0.2 mg / kg / hnub, n=89 ), thiab placebo (n{14}}).

Lub hnub nyoog nruab nrab ntawm cov neeg mob cuv npe yog 13 xyoo; 29 feem pua ​​​​tau ntau dua lossis sib npaug rau 18 xyoo, noj 1-4 AEDs, thiab yav tas los sim lossis txiav tawm qhov nruab nrab ntawm 7 lwm yam AEDs. Qhov nruab nrab qhov nruab nrab lub caij nplooj zeeg zaus zaus hauv txhua pab pawg yog 77 ntu hauv ib hlis. Tom qab tsim 4-lub limtiam lub hauv paus pib lub caij nplooj zeeg zaus zaus, cov neeg mob randomized titrated lawv cov koob tshuaj ntau dua 2-lub limtiam titration lub sijhawm, ua raws li 12-lub limtiam lub sijhawm tu-dose. Cov neeg mob uas ua tiav Tshooj 1 tau tsim nyog nkag mus rau Tshooj 2 ntawm qhov kev sim tshuaj ntsuam xyuas, kev tshawb fawb qhib-daim ntawv txuas ntxiv mus ntev li 12 lub hlis txhawm rau ntsuas qhov kev nyab xeeb mus ntev, kev ua siab ntev thiab kev ua tau zoo ntawm Fintepla.

Cov txiaj ntsig tau pom tias txoj kev tshawb fawb tau ntsib nws cov ntsiab lus tseem ceeb: Fintepla {{0}}.7 mg / kg / hnub yog qhov zoo tshaj rau cov placebo hauv kev txo qis qis qis (hloov ntau zaus ntawm kev ntog) raws li kev hloov pauv hauv cov hauv paus thiab titration thiab tu lub sijhawm kho. Qhov nruab nrab hloov pauv los ntawm kev txo qis hauv paus: 26.5 feem pua ​​​​vs 7.8 feem pua ​​, p=0 0012), cov ntaub ntawv tseem ceeb heev. Siv cov kev ntsuas parametric, qhov nruab nrab txhua hli zaus ntawm kev poob hauv Fintepla (0.7 mg / kg / hnub) pab pawg kho mob tau txo los ntawm 26.5 feem pua ​​​​piv rau cov placebo pawg (p=0.0034). Tsis tas li ntawd, Fintepla (0.7 mg / kg / hnub) kuj tau pom qhov kev txhim kho tseem ceeb piv rau cov placebo hauv cov kev ntsuas tseem ceeb thib ob, suav nrog kev faib ua feem ntawm cov neeg mob uas muaj qhov txo qis hauv kev kho mob (Ntau dua lossis sib npaug li 50 feem pua) hauv qhov zaus ntawm kev poob. ( 25.3 feem pua ​​​​vs 10.3 feem pua ​​, p=0.0165), qhov feem pua ​​​​ntawm cov neeg mob uas pom kev txhim kho los ntawm cov hauv paus hauv Kev Kho Mob Ntiaj Teb Txhim Kho Score (CGI-I) (48.8 feem pua ​​vs 33.8 feem pua ​​, p{{ 28}}.0567), thiab qhov feem pua ​​​​ntawm cov neeg mob uas tau pom tias muaj kev txhim kho tseem ceeb hauv CGI-Kuv los ntawm qhov pib. Tus nqi ntawm cov neeg mob (26.3 feem pua ​​vs 6.3 feem pua ​​, p=0.0007).

Lwm qhov kawg ntawm qhov kawg ntawm txoj kev tshawb no: Fintepla qis{{0}} koob tshuaj (0.2 mg/kg/hnub) txo qhov zaus ntawm kev poob los ntawm 13.2 feem pua ​​​​ntawm ib lub hlis los ntawm cov kab hauv qab mus rau kev kho mob, tab sis qhov kev hloov pauv no tsis ncav cuag qhov tseem ceeb ntawm cov ntaub ntawv. piv nrog cov placebo (p=0.0915). Fintepla feem ntau zam tau zoo nyob rau hauv txoj kev tshawb no, nrog rau cov xwm txheej tsis zoo ib yam nrog cov uas tau pom hauv lub tuam txhab ob qhov kev tshawb fawb dhau los ntawm Phase III hauv Dravet syndrome.