Lisaftoclax (APG-2575) Yalandira Chivomerezo Choyamba Chokhazikika ku China cha CLL/SLL, Chosonyeza Kukula Kwambiri Padziko Lonse mu Chithandizo cha Bcl-2 Inhibitor

Posachedwapa, Ascentage Pharma yalengeza kuti mankhwala ake atsopano a Bcl-2 selective inhibitor lisaftoclax (APG-2575) avomerezedwa ndi National Medical Products Administration (NMPA) ku China kuti athandize odwala akuluakulu omwe ali ndi matenda a chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) omwe adalandirapo chithandizo chimodzi cha systemic kuphatikizapo Bruton's tyrosine kinase (BTK) inhibitors, zomwe zimapangitsa lisaftoclax kukhala mankhwala oyamba a Bcl-2 oletsa kulandira chilolezo chovomerezeka ndi chilolezo chotsatsa chithandizo cha odwala omwe ali ndi CLL/SLL ku China, komanso mankhwala achiwiri a Bcl-2 oletsa ovomerezeka padziko lonse lapansi.

Lisaftoclax ndi mankhwala atsopano oletsa khansa a Bcl-2 omwe amaperekedwa pakamwa, omwe adapangidwa ndi Ascentage Pharma kuti achiritse odwala khansa mwa kuletsa puloteni yoletsa khansa ya Bcl-2 ndikubwezeretsa njira yachibadwa ya apoptosis m'maselo a khansa. Mu mayeso azachipatala, lisaftoclax yawonetsa kuthekera kwakukulu kochiritsira khansa zingapo zamagazi ndi zotupa zolimba, makamaka mu CLL/SLL, zonse monga monotherapy komanso kuphatikiza.

Kuvomerezedwa kumeneku kumachokera ku zotsatira za kafukufuku wofunikira kwambiri wa Gawo Lachiwiri (APG2575CC201) womwe unapangidwa kuti uwonetse momwe lisaftoclax imagwirira ntchito komanso chitetezo chake mwa odwala omwe ali ndi CLL/SLL yobwereranso m'mbuyo kapena yokana chithandizo, ndipo chiŵerengero cha mayankho onse (ORR) ndicho chimake chachikulu. Lisaftoclax inasonyeza mphamvu yogwira ntchito bwino komanso ORR yomwe inakwaniritsa cholinga chake mwa odwala omwe kale ankalandira mankhwala oletsa BTK ndi/kapena immunochemotherapy. Kuphatikiza apo, lisaftoclax inasonyeza chitetezo chabwino popanda chotupa-lysis syndrome (TLS) chomwe chimachitika panthawi ya kafukufukuyu, kuchuluka kochepa kwa poizoni m'magazi komwe kunali koyenera kuchiritsidwa, komanso kuchuluka kochepa kwa poizoni wosakhala m'magazi komwe kunali kwakukulu kwambiri mu kalasi 1-2.

CLL/SLL ndi khansa ya m'magazi yomwe imayamba chifukwa cha maselo okhwima a B-cell. Imakhudza makamaka okalamba omwe ali ndi matenda atsopano opitilira 100,000 omwe amanenedwa padziko lonse lapansi chaka chilichonse1. Ku China, komwe kuchuluka kwa matenda a CLL/SLL kuli kotsika kuposa kwa mayiko akumadzulo, matendawa akuchitika mofulumira kwambiri, ndipo ali ndi zaka zazing'ono komanso ankhanza kwambiri2. Monga njira yoyamba yochizira CLL/SLL, zoletsa za BTK zasintha kwambiri zotsatira za chithandizo kwa odwala. Komabe, zoletsa za BTK zikukumanabe ndi mavuto osiyanasiyana monga kuthekera kochepa koyambitsa mayankho akuya, chiopsezo chachikulu chobwereranso chithandizo chapakati ndi cha nthawi yayitali, poizoni komanso kusalekerera komwe kumayenderana ndi chithandizo cha nthawi yayitali; motero, kufunikira njira zochizira zotetezeka komanso zothandiza kwambiri kwa odwala omwe ali ndi CLL/SLL.

Kuyambitsa zoletsa za Bcl-2 kwasintha kwambiri chithandizo cha CLL/SLL. Bcl-2 yomwe imayambitsa apoptosis, yomwe imapezeka kwambiri m'matenda osiyanasiyana a khansa ya m'magazi, makamaka CLL/SLL, ndi njira yofunika kwambiri yomwe maselo otupa amapewera apoptosis. Komabe, kupeza choletsa cha Bcl-2 ngati cholinga chochiritsira n'kovuta kwambiri makamaka chifukwa njira yake yogwirira ntchito imadalira mgwirizano wa mapuloteni ndi mapuloteni (PPI). Kulumikizana kwa Bcl-2 ndi kwakukulu, zomwe zimapangitsa kuti zikhale zovuta kuti zoletsa za mamolekyulu ang'onoang'ono zigwire ntchito zoletsa. Kuphatikiza apo, puloteni ya Bcl-2 ili pa mitochondria, yokhala ndi kapangidwe ka nembanemba kawiri, ndi imodzi mwa zigawo zovuta kwambiri komanso zovuta zamaselo chifukwa zimafuna mankhwala kuti alowe kaye mu nembanemba ya selo asanayambe kugwira ntchito pa nembanemba ya mitochondrial. Izi zisanachitike, palibe choletsa cha Bcl-2 chomwe chidavomerezedwa kuti chichiritse CLL/SLL ku China. Kuvomerezedwa kumeneku kwa lisaftoclax kumadzaza kusiyana kwa chithandizo mu CLL/SLL, kubweretsa chiyembekezo chatsopano kwa odwala ambiri mdzikolo.

Pakadali pano, pali mayesero ambiri azachipatala a ukadaulo watsopano wothana ndi khansa ku China omwe akufuna odwala. Mukafunsira mankhwala ndi ukadaulo watsopano, mutha kulumikizana ndi Dipatimenti Yapadziko Lonse ya Chipatala cha Oncology ku Beijing South Region.

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