Pi bon-an-klas GnRH rcepteur Antagonist Yselty (linzagolix) Aplike pou lis nan Inyon Ewopeyen an

ObsEva SA se yon konpayi biopharmaceutiical Swis biopharmaceutiical dedye a devlopman ak komesyalizasyon nan terapi nouvo amelyore sante repwodiksyon fi. Denyeman, konpayi an te anonse ke li te soumet yon aplikasyon otorizasyon maketing (MAA) pou Yselty (linzagolix 100mg ak 200mg) nan Ajans medsin Ewopeyen an (EMA), ki se itilize yo trete lou manstrual senyen ki asosye ak fibroid teritwa (Lou Menstrual Senyen). , HMB). ObsEva plan yo soumet Nouvo Aplikasyon Dwog Yselty a (NDA) nan US FDA a nan dezyem mwatye nan 2021.

Linzagolix aktif Yselty a famasetik linzagolix (ansyen li te ye kom OBE2109) se yon nouvo, oral, yon fwa-chak jou GnRH resepte antagonist ak potansyelman pi bon-an-klas karakteristik. Kounye a, linzagolix se nan etap nan an reta nan devlopman klinik pou tretman an nan menorrhagia (HMB) ki asosye ak fibwoyid teritwa ak doule ki asosye ak andometrioz. ObsEva te jwenn lisans linzagolix ki soti nan Kissei nan fen 2015 epi li te jwenn dwa pou komesyalize pwodwi a atrave lemond (eksepte Azi).

Si apwouve, Yselty ap vin antagonist la selman GnRH ak yon rejim doz fleksib pou tretman an nan fibwoyid teritwa: (1) 100mg yon fwa pa jou, apwopriye pou kontrent oswa gen tandans pou fe pou evite itilize nan monn ajoute-back terapi (ajoute -back terapi, ABT) pou pasyan fi; (2) 200 mg yon fwa yon jou konbine avek ABT, apwopriye pou itilize alontem (plis pase mwa 6); (3) 200 mg yon fwa pa jou pou itilize kout tem, apwopriye pou rediksyon rapid nan volim fibroid.

Faz Yselty a 3 pwoje klinik pou tretman an nan fibroid teritwa gen ladan 2 ese klinik kle (PRIMROSE 1 ak PRIMROSE 2). Etid sa yo te rive krite yo sikse: ba-doz ak linzagolix-wo doz nan konbinezon ak ak san ABT ka efektivman trete HMB ki asosye ak fibroid teritwa, epi yo gen benefisye ki akseptab.

estrikti chimik linzagolik

Jijman PRIMROSE 1 te fet nan Etazini ak enskri yon total de 574 fanm ki gen fibroid terib; 2 pwose PRIMROSE 2 a te fet nan Ewop ak Etazini, ak yon total de 535 fanm ki gen fibwom terib te enskri. Nan tou de ese klinik, pasyan yo te bay 100mg oswa 200mg nan linzagolix (ak ak san ABT a monn) oswa plasebo. Pwen prensipal de eprev yo te rediksyon an nan HMB nan semen 24 nan tretman; sekouris yo te defini kom: pasyan ki mezire le li sevi avek emoglobin alkalin, pet san menstrual (MBL) ≤80 mL ak MBL diminye pa ≥50% soti nan debaz. Pwen segonde enkli amenorhea, tan MBL rediksyon, emoglobin (Hb), doule, ak bon jan kalite nan lavi (QoL). Sekirite pwen yo enkli dansite zo (BMD) ak evenman negatif (AE). Pa gen kalsyom / vitamin D te bay pandan peryod etid la. Te dansite mineral Zo mezire pa doub-eneji X-ray absorptiometry (DEXA) eskane nan debaz, semen 24, semen 52, ak semen 76 (evalye mwa 6 apre tretman).

Rezilta yo te montre ke tou de ese avek sikse te rankontre pwensipal la: konpare ak plasbo, tout gwoup doz te estatistik ak klinikman siyifikatif rediksyon nan HMB. Etid la te jwenn ke linzagolix gen yon repons kle-doz-doz, ak pousantaj la repons prensipal pi wo prensipal te obseve nan fanm ki ap resevwa 200 mg mg konbine avek ABT. An tem de pwen segonde (amenorrhea, tan MBL rediksyon, nivo emoglobin nan pasyan ki gen anemi, doule, bon jan kalite nan lavi), tout doz te montre amelyorasyon enpotan. Volim nan matris ak fibroid nan gwoup la 200 mg doz diminye rapidman ak anpil siyifikativman.

Nan jijman an PRIMROSE 1, pousantaj repons lan nan gwoup la 200mg + ABT te 75.5 % (p<0.001), the="" response="" rate="" of="" the="" 100mg="" (no="" abt)="" group="" was="" 56.4%="" (p="0.003)," and="" the="" placebo="" group="" was="" 35.0%.="" the="" overall="" safety="" profile="" was="" in="" line="" with="" expectations,="" and="" the="" most="" common="" adverse="" events="" (occurring="" in="" more="" than="" 5%="" of="" patients)="" were="" headaches="" and="" hot="" flashes.="" the="" average="" percentage="" change="" from="" baseline="" in="" bmd="" is="" small,="" which="" is="" consistent="" with="" any="" gnrh="" antagonist="">

Nan PRIMROSE 2 jijman an, pousantaj repons 200mg + ABT gwoup la te 93.9 (p<0.001), the="" response="" rate="" of="" the="" 100mg="" (no="" abt)="" group="" was="" 56.7%=""><0.001), and="" the="" placebo="" group="" was="" 29.4%.="" the="" overall="" safety="" profile="" was="" in="" line="" with="" expectations,="" and="" the="" most="" common="" adverse="" events="" (occurring="" in="" more="" than="" 5%="" of="" patients)="" were="" headaches="" and="" hot="" flashes.="" the="" average="" percentage="" change="" from="" baseline="" in="" bmd="" is="" small,="" which="" is="" consistent="" with="" previous="" clinical="" trials.="" the="" 52-week="" results="" showed="" that="" continuous="" linzagolix="" treatment="" can="" continuously="" and="" effectively="" reduce="" hmb.="" the="" response="" rates="" of="" the="" 200mg+abt="" group="" and="" 100mg="" (without="" abt)="" group="" were="" 91.6%="" and="" 53.2%,="" respectively.="" in="" addition,="" compared="" with="" the="" 24th="" week,="" a="" small="" incremental="" change="" in="" bmd="" was="" observed="" in="" the="" 52nd="">