Fennec lub tuam txhab Pedmark (sodium thiosulfate) rov xa nws daim ntawv thov npe hauv Tebchaws Meskas!

Fennec Pharmaceuticals tsis ntev los no tshaj tawm tias nws tau rov xa daim ntawv thov tshuaj tshiab (NDA) rau Pedmark (tshwj xeeb tsim cov tshuaj sodium thiosulfate) mus rau Asmeskas Khoom Noj thiab Tshuaj Yeeb Tshuaj (FDA), uas tau siv rau hauv cov neeg mob menyuam yaus txhawm rau tiv thaiv platinum uas muaj tshuaj kho mob. Ototoxicity, tshwj xeeb: rau cov neeg mob uas muaj qhov txwv, tsis nthuav dav cov qog nqaij hlav los ntawm 1 hlis txog 18 xyoos, txhawm rau tiv thaiv ototoxicity tshwm sim los ntawm kev siv tshuaj cisplatin.

Tom qab tau txais cov feeb kawg ntawm Chav Kawm Lub Rooj Sib Tham nrog FDA, Pedmark NDA xa nws dua. Nws yog ib qho tseem ceeb uas tsab ntawv teb ua tiav (CRL) tau txais thaum Lub Yim Hli 10, 2020 tau hais txog qhov tsis zoo ntawm cov chaw tsim tshuaj lag luam, tab sis tsis pom muaj teeb meem kev nyab xeeb lossis teeb meem muaj txiaj ntsig, thiab tsis xav tau cov ntaub ntawv kho mob ntxiv.

Pedmark yog tshuaj yeeb tshuaj, uas yog dej-soluble thiol sib xyaw siv ua tshuaj txo cov tshuaj. Kev tswj hwm lub sijhawm ntev (4-8 teev) thiab Pedmark koob tshuaj ntau (16-20g/m2) tuaj yeem tiv thaiv tsiaj qauv thiab cov neeg mob los ntawm kev tiv thaiv kab mob. Ototoxicity induced los ntawm platinum.

Yog pom zoo, Pedmark yuav yog thawj cov khoom los tiv thaiv menyuam yaus&#kev hnov ​​lus tsis zoo los ntawm cisplatin. Yav dhau los, FDA tau tso cai Pedmark Orphan Drug Designation, Kev Teev Npe Ceev, thiab Kev Txhim Kho Tshuaj. Tam sim no, cov tshuaj (European lub npe lag luam: Pedmarqsi) tseem tab tom tshuaj xyuas los ntawm European Medicines Agency (EMA).

Rosty Raykov, CEO ntawm Fennec Pharmaceuticals, hais tias:" Peb zoo siab rov xa NDA rau Pedmark. Peb tos ntsoov yuav ua haujlwm nrog FDA thaum lub sijhawm tshuaj xyuas. Peb tseem cog lus tias yuav txo qis kev pheej hmoo ntawm kev hnov ​​lus tas mus li hauv cov menyuam tau txais kev kho mob cisplatin. Nrog kev pom zoo, Pedmark yuav dhau los ua thawj qhov kev pom zoo los ntawm FDA los txo qis kev pheej hmoo ntawm cisplatin-induced ototoxicity rau menyuam yaus."

Cisplatin thiab lwm yam platinum sib txuas yog cov tshuaj siv tshuaj kho mob rau ntau yam kev mob qog noj ntshav thaum yau. Hmoov tsis zoo, kev kho platinum-based tuaj yeem ua rau ototoxicity lossis tsis hnov ​​lus, uas yog qhov ruaj khov, tsis hloov pauv, thiab tshwj xeeb tshaj yog teeb meem rau cov muaj txoj sia nyob ntawm kev mob qog noj ntshav thaum yau.

Hauv Tebchaws Meskas thiab Europe, kwv yees tias ntau dua 10,000 tus menyuam tau txais tshuaj platinum-based tshuaj txhua xyoo. Ntawm lawv, 40% -90% ntawm cov menyuam yuav muaj ototoxicity hnyav thiab hloov tsis tau. Qhov tshwm sim ntawm ototoxicity hauv cov menyuam no nyob ntawm qhov koob tshuaj thiab ntev npaum li cas ntawm kev siv tshuaj kho mob, thiab ntau tus menyuam no xav tau lub pob ntseg mloog tas mus li. Tam sim no tsis muaj tshuaj uas tuaj yeem tiv thaiv qhov hnov ​​tsis hnov ​​lus no. Tsuas yog kim, thev naus laus zis nyuaj, suboptimal cochlear implants (puab pob ntseg) cog tau pom los muab qee yam txiaj ntsig. Ntawm cov neeg mob nrog ototoxicity nyob rau theem tseem ceeb ntawm kev txhim kho, menyuam mos thiab menyuam yaus tsis muaj kev hais lus thiab kev txhim kho lus thiab kev txawj nyeem ntawv, thiab cov menyuam yaus thiab cov tub ntxhais hluas tsis muaj kev txhim kho hauv zej zog thiab kev xav thiab kev kawm tiav.

Pedmark tau raug tshuaj xyuas los ntawm pab pawg koom tes hauv 2 theem III kev tshawb fawb soj ntsuam rau kev tiv thaiv thiab txo qis ntawm ototoxicity, suav nrog COG ACCL0431 txoj kev kawm thiab SIOEL 6 txoj kev tshawb fawb. Ob txoj kev tshawb fawb tau ua tiav tiav. Txoj kev tshawb nrhiav COG ACCL0431 suav nrog 5 hom mob qog noj ntshav thaum yau. Cov qog nqaij hlav no feem ntau kho nrog tshuaj kho mob cisplatin los kho cov kab mob hauv ib cheeb tsam thiab nthuav tawm, suav nrog kev kho mob tshiab hepatoblastoma, qog nqaij hlav qog nqaij hlav, osteosarcoma, neuroblastoma, thiab medulla Cell qog. SIOPEL 6 txoj kev tshawb fawb tsuas tso npe rau cov neeg mob hepatoblastoma nrog cov qog nqaij hlav hauv ib cheeb tsam.

Pedmark cov ntaub ntawv sim tshuaj

Pedmark tuaj yeem tiv thaiv cov hlwb los ntawm cov tshuaj lom platinum ntau txoj hauv kev. Cov txheej txheem tiv thaiv tshuaj lom neeg no tsis yog ib leeg tshwj xeeb. Pedmark tuaj yeem tsis ua haujlwm platinum complexes thiab ua rau lawv covalently khi rau thiols yam tsis muaj cytotoxicity. Txawm hais tias muaj ntau ntau ntawm cov platinum dawb hauv cov ntshav ncig tau ploj tom qab 4 teev ntawm kev tswj hwm platinum, Pedmark' kev tiv thaiv platinum cuam tshuam txog kev hnov ​​lus tseem ua tau zoo tom qab 8 teev ntawm kev tswj hwm qeeb ntawm platinum. Qhov no qhia tias Pedmark tuaj yeem khi rau cov platinum/cov protein ntau, yog li ua kom nws qhov lom tsawg. Lub peev xwm txheej txheem ntawm platinum ua rau hnov ​​tsis hnov ​​lus yog vim qhov tso cov protein-khi platinum hauv cochlea.

Pedmark' lwm txoj hauv kev los tiv thaiv ototoxicity yog los ntawm kev tshem tawm cov pa oxygen (ROS) thiab nce qib ntawm cov tshuaj txo qis endogenous (xws li GSH). Hauv lub pob ntseg sab hauv, cochlea tuaj yeem mloog zoo Pedmark hauv perilymph lossis endolymph, thiab hauv zos txhim kho Pedmark' tshuaj tiv thaiv tiv thaiv ototoxicity. Yog li ntawd, cisplatin-mediated (ntawm ROS) plaub hau cell apoptosis raug cuam tshuam los ntawm kev txo cov khoom ntawm sodium thiosulfate (STS).