Livtencity: Thawj cov tshuaj siv rau kev kho cov kab mob refractory CMV hauv cov neeg tau txais kev hloov pauv!--1/2

Takeda Pharmaceuticals (Takeda) tsis ntev los no tau tshaj tawm tias US Food and Drug Administration (FDA) tau pom zoo cov tshuaj tiv thaiv kab mob Livtencity (maribavir, TAK-620) rau kev kho mob ntawm cov neeg txais kev hloov pauv uas yog refractory rau cov pa tshuaj tiv thaiv kab mob (nrog lossis tsis muaj noob). Hom tsis kam) tom qab hloov pauv nrog cytomegalovirus (CMV) kab mob. Livtencity tshwj xeeb yog tsim rau: cov neeg laus thiab menyuam yaus (hnub nyoog ≥ 12 xyoos, qhov hnyav ≥ 35 kg) uas tau txais kev hloov pauv hauv nruab nrog cev (SOT) lossis hematopoietic stem cell transplantation (HSCT), kev kho mob ntawm ganciclovir [ganciclovir], valganciclo Viral. [valganciclovir], foscarnet [foscarnet], cidofovir [cidofovir] refractory (nrog lossis tsis muaj genotype resistance) CMV kab mob tom qab hloov pauv. Livtencity blocks viral replication los ntawm inhibiting kev ua ntawm CMV protein kinase pUL97.

Nws yog ib qho tsim nyog hais tias Livtencity yog thawj zaug thiab tsuas yog cov tshuaj pom zoo los ntawm US FDA rau kev kho mob ntawm CMV kab mob tom qab hloov pauv uas yog refractory rau cov tshuaj tiv thaiv kab mob (nrog lossis tsis muaj genotype resistance). Livtencity tau pom zoo los ntawm cov txheej txheem tshuaj xyuas tseem ceeb thiab yav dhau los tau tso cai Orphan Drug Designation (ODD) thiab Breakthrough Drug Designation (BTD) los ntawm FDA. Tam sim no, Livtencity tseem nyob rau theem 3 kev sim tshuaj raws li kev kho thawj kab rau CMV kab mob hauv HSCT cov neeg tau txais kev hloov pauv. CMV yog DNA virus ntawm β herpesvirus subfamily, nrog rau qib siab ntawm hom tshwj xeeb. Tib neeg yog tib tus tswv tsev ntawm tib neeg cytomegalovirus (HCMV). CMV yog ib yam kab mob uas kis tau rau tib neeg txhua lub hnub nyoog. Thaum muaj hnub nyoog 40 xyoo, ntau tshaj li ib nrab ntawm cov neeg laus tau kis tus kab mob CMV, thiab feem ntau tsis muaj tsos mob lossis qhia tau. Txawm li cas los xij, hauv cov neeg uas tsis muaj zog tiv thaiv kab mob (xws li cov neeg tau txais kev hloov pauv hauv nruab nrog cev los yog qia cell), tus kab mob CMV yog ib qho teeb meem loj heev.

CMV yog ib qho ntawm feem ntau thiab mob hnyav tom qab hloov pauv, nrog qhov tshwm sim ntawm 16-56% hauv cov neeg tau txais kev hloov pauv hauv nruab nrog cev thiab li ntawm 30% -70% hauv cov neeg tau txais hematopoietic qia cell. CMV tuaj yeem tau txais lossis rov ua haujlwm dua tom qab hloov pauv, uas tuaj yeem cuam tshuam tsis zoo rau tus neeg tau txais kev hloov pauv thiab ua rau muaj qhov tshwm sim loj, suav nrog kev puas tsuaj ntawm cov kabmob hloov pauv thiab tsis ua haujlwm ntawm kev hloov pauv. Cov neeg tau txais kev hloov pauv tau ntsib tus kab mob CMV muaj kev pheej hmoo siab dua ntawm cov teeb meem thiab kev tuag. Cov tshuaj tiv thaiv kab mob uas twb muaj lawm tuaj yeem siv los kho CMV, tab sis cov kev kho mob no yuav raug txwv hauv lawv daim ntawv thov vim muaj kev phiv thiab / lossis tshuaj tiv thaiv. CMV kab mob uas tiv taus lossis tsis teb rau cov tshuaj uas twb muaj lawm yog qhov kev txhawj xeeb ntau dua. Qhov kev pom zoo no yuav muab kev xaiv kho mob rau pab pawg neeg mob no thiab pab ua kom tau raws li qhov xav tau kev kho mob tseem ceeb hauv daim teb no.

Cov tshuaj nquag ntawm Livtencity yog maribavir, uas yog qhov ncauj bioavailable anti-cytomegalovirus (CMV) compound, thiab tsuas yog CMV cov tshuaj tiv thaiv kab mob uas lub hom phiaj thiab inhibits pUL97 protein kinase thiab nws cov substrate ntuj. Kev tswj hwm CMV tam sim no muaj feem cuam tshuam nrog kev lag luam nyuaj, suav nrog kev tswj cov tshuaj toxicity thiab viremia clearance. Livtencity muaj peev xwm rov hais dua cov kev kho mob ntawm refractory CMV tom qab hloov pauv, tsis hais qhov kev tiv thaiv.

Qhov kev pom zoo no yog nyob ntawm theem 3 TAK-620-303 (SOLSTICE, NCT02931539) tseem ceeb. Cov txiaj ntsig tseem ceeb tau tshaj tawm ntawm 2021 Kev Hloov Kho thiab Kho Mob Cell (TCT) Lub Rooj Sib Tham hauv Lub Ob Hlis xyoo no. Cov txiaj ntsig ntawm pawg kev tshuaj xyuas pawg tau tshaj tawm nyob rau lub Peb Hlis xyoo no. Tshaj tawm ntawm 47th Lub Rooj Sib Tham Txhua Xyoo ntawm European Society for Blood and Bone Marrow Transplantation (EBMT) hauv 2021. Cov txiaj ntsig tseem ceeb qhia tau tias maribavir muaj txiaj ntsig zoo dua piv nrog cov tshuaj tiv thaiv kab mob sib kis (IAT), mus txog qhov tseem ceeb thiab cov ntsiab lus tseem ceeb thib ob ntawm txoj kev tshawb no. . Tsis tas li ntawd, maribavir muaj kev kho mob toxicity qis dua piv nrog cov tshuaj tiv thaiv kab mob. Cov txiaj ntsig ntawm kev txheeb xyuas pawg pab pawg txhawb nqa kev ua tau zoo hauv tag nrho cov pej xeem randomized.

Ramona Sequeira, Tus Thawj Coj ntawm Takeda Pharmaceutical's US Chaw Lag Luam thiab Kev Lag Luam Thoob Ntiaj Teb Kev Lag Luam, tau hais tias: "Qhov kev pom zoo niaj hnub no yuav rov hais dua kev tswj hwm ntawm CMV tom qab hloov pauv. Livtencity yog thawj zaug thiab tsuas yog siv los kho cov neeg txais kev hloov pauv nrog lossis tsis muaj tshuaj tiv thaiv. Cov tshuaj tiv thaiv kab mob CMV tom qab hloov pauv. Cov neeg mob hloov chaw muaj kev kho mob ntev thiab nyuaj; Nrog rau qhov kev pom zoo no, peb zoo siab los muab cov neeg mob no nrog cov tshuaj tiv thaiv kab mob hauv qhov ncauj tshiab los tawm tsam CMV kab mob thiab kab mob. Peb ua tsaug rau cov neeg mob thiab cov kws kho mob uas tau koom nrog hauv peb qhov kev sim tshuaj, nrog rau peb cov kws tshawb fawb thiab cov kws tshawb fawb rau lawv txoj kev koom tes."

maribavir molecular qauv