GlaxoSmithKline thawj qhov adhesion inhibitor Rukobia (fostemsavir) yuav pom zoo sai sai hauv EU

ViiV Kev Noj Qab Haus Huv yog kev tshawb nrhiav kab mob HIV / AIDS tshuaj thiab kev txhim kho tshuaj uas tswj los ntawm GlaxoSmithKline (GSK) thiab Pfizer thiab Shionogi. Tsis ntev los no, lub tuam txhab tshaj tawm tias Pawg Neeg Sawv Cev Saib Xyuas European Tshuaj (EMA) rau Cov Khoom Siv Tshuaj rau Cov Neeg Siv (CHMP) tau tshaj tawm cov lus pom zoo hais txog kev pom zoo rau Rukobia (fostemsavir) 600mg kho mob-tso tshuaj, nrog rau lwm cov tshuaj tiv thaiv kab mob (ARV), Txog kev kho mob rau cov neeg laus muaj ntau yam tshuaj tiv thaiv HIV-1 uas tsis tuaj yeem tsim qhov kev tiv thaiv tshuaj tiv thaiv kab mob.

Rukobia yog ib qho tshiab muab tso ua ke tiv thaiv kev kho mob HIV-1. Lub Rau Hli xyoo no, Rukobia tau pom zoo los ntawm Asmeskas FDA rau kev taw qhia: ua ke nrog lwm cov tshuaj ARV rau kev kho mob ntawm cov neeg mob uas tau sim ntau txoj kev kho mob HIV (ntau kev kho mob-paub txog, HTE) thiab vim yog cov tshuaj tiv thaiv / tsis quav cawv lossis kev nyab xeeb. Xav txog ntau tus neeg laus tshuaj tiv thaiv HIV-1 uas tsis ua haujlwm nrog cov tshuaj tua kabmob ARV tam sim no. Hauv kev piv rau Theem III BRIGHT kawm, feem ntau (60 %) HTE muaj ntau hom tshuaj tiv thaiv HIV-1 cov neeg laus muaj tus kabmob tau txais Rukobia thiab kho cov kev kho mob tom qab kom ua tiav thiab muaj kev tiv thaiv kab mob kis mus txog 96 lub lis piam, thiab CD4+ T cell technology yog qhov chaw kho mob muaj cov ntsiab lus kev txhim kho.

Kev nce qib ntau nyob hauv ob peb xyoo dhau los tau txhim kho kev kho mob HIV ntau heev, thiab rau ntau tus neeg mob, tus kabmob HIV yog suav tias yog kev tswj kav tus neeg muaj sia nyob ntev. Txawm li cas los xij, vim kev siv tshuaj tiv thaiv, tiv taus lossis kev txiav txim siab txog kev nyab xeeb, cov neeg mob HTE laus (li ntawm 6% ntawm cov neeg muaj tus kabmob HIV) muaj tsawg los tsis muaj thiab tsis muaj kev pheej hmoo rau mob AIDS thiab tuag thiab kev tuag ntxiv, thiab kev kho mob ntxiv yog qhov yuav tsum tau ua sai.

Kev pom zoo ntawm Rukobia ntawm kev ua lag luam yuav muab cov kev kho mob tseem ceeb rau cov neeg muaj mob HTE multidrug-resistant HIV-1 uas tsis tuaj yeem siv cov tshuaj uas twb muaj lawm los txhawm thiab tswj kev tiv thaiv kab mob vim muaj ntau yam. Yav dhau los, Asmeskas FDA tau tso cai Rukobia taug qab kev ceev ceev, kev soj ntsuam kev txheeb xyuas kev ua ntej, thiab dhau kev ua txhaum cai tshuaj. European Union EMA tau tso cai Rukobia cov kev tsim nyog rau kev ntsuam xyuas nrawm.

Rukobia' s lub tshuaj kws ua haujlwm tau zoo yog fostemsavir, uas yog thawj-chav kawm HIV-1 txuas inhibitor. Fostemsavir yog prodrug ntawm temsavir. Tom qab kev tswj hwm ntawm qhov ncauj, fostemsavir tuaj yeem hloov mus rau temsavir, uas tom qab ntawd nqus tau thiab siv cov tshuaj tiv thaiv kab mob los ntawm kev ncaj qha rau glycoprotein 120 (gp120) subunit ntawm tus kab mob saum npoo. Los ntawm kev khi rau qhov chaw ntawm tus kabmob no, temsavir tiv thaiv tus kabmob HIV los ntawm kev ua lub cev rau cov kabmob tiv thaiv kabmob CD4+ T thiab lwm yam kev tiv thaiv kabmob, thiab tiv thaiv tus kabmob HIV los ntawm kev xa mus rau cov hlwb thiab nthuav tawm zuj zus. Txij li Rukobia yog thawj qhov kev siv tshuaj tiv thaiv kab mob rau thawj kauj ruam (txuas ntxiv) ntawm lub voj voog tus kab mob, nws tsis tau pom tias nws tawm tsam lwm hom tshuaj tiv thaiv kab mob, uas tuaj yeem pab tsim kev tiv thaiv feem ntau lwm cov tshuaj tiv thaiv kab mob HIV.

30 xyoo dhau los, kev txhim kho tsis txaus ntseeg tau ua rau kev kho mob HIV. Cov tshuaj tiv thaiv kab mob tuaj yeem tiv thaiv HIV tau zoo, uas yuav pab txo qis kev muaj mob, kis tus kabmob HIV, thiab kev tuag mob ntsig txog AIDS. Txawm li cas los xij, vim tias muaj peev xwm hloov pauv ntawm HIV, qee tus neeg mob tuaj yeem tsim kho cov tshuaj tiv thaiv kab mob, ua rau Nws txoj kev kho mob ua tsis tiav. Cov kev sib tw hauv kev tiv taus, kev nyab xeeb, thiab kev sib txuam tshuaj yuav txo tau ntau cov tshuaj tiv thaiv kev tsis haum thaum tsim cov kev xaiv zoo rau kev kho mob. Kuj tseem muaj kev xav tau kev kho mob tsis tseem ceeb rau cov neeg mob ntau hom tshuaj uas yav tas los tau txais ntau txoj haujlwm thiab tsis tuaj yeem tawm tsam tus kabmob HIV tau zoo. Qhov kev ua tau zoo thiab kev nyab xeeb tshawb fawb los ntawm Rukobia qhov chaw tsim kho kev ua haujlwm qhia tau tias cov tshuaj muaj lub peev xwm rau cov neeg muaj ntau yam tshuaj tiv thaiv mob HIV uas xav tau txoj kev kho tshiab. Rukobia kev pom zoo rau kev ua lag luam yuav muab txoj hauv kev tshiab los pab cov neeg mob li no ua tiav kev tsim txom kev tsuj.

Fostemsavir qauv qog

Kev tshuaj xyuas zoo ntawm CHMP yog saib raws cov ntaub ntawv los ntawm piv piv Phase III BRIGHT kawm (NCT02362503) hauv HTE ntau cov tshuaj tiv thaiv HIV rau cov neeg mob. 96 lub limtiam cov txiaj ntsig ntawm qhov kev tshawb fawb tau tshaj tawm ntawm 2019 International AIDS Society AIDS Science Science (IAS 2019) hauv Mexico City thaum Lub Xya Hli 2019.

BRIGHT yog kev kawm ob-pawg (xaiv thiab tsis-randomized) uas soj ntsuam kev nyab xeeb thiab ua tau zoo ntawm HIV-1 txuas inhibitor fostemsavir hauv kev kho dua dhau los (HTE) HIV-1 laus cov neeg laus. Tag nrho ntawm 371 tus neeg mob tau tso npe rau hauv txoj kev tshawb no. Txawm hais tias cov neeg mob no tau siv tshuaj tiv thaiv antiretroviral (ARV), lawv cov ntshav ntawm cov kab mob (HIV-RNA) tseem muaj feem ntau. Cov neeg mob feem ntau tau txais kev kho mob HIV rau ntau dua 15 xyoo (71%), tau txais 5 lossis ntau dua kev kho mob HIV (85%) thiab / lossis muaj keeb kwm ntawm AIDS (86%) ua ntej nkag mus hauv kev sim siab.

Txhua tus neeg mob sau cia tshuaj, tiv thaiv tsis tau thiab / lossis contraindications rau 4 ntawm 6 qhov tam sim no muaj ARV tshuaj. Hauv kev sib koom tes hauv pawg (n = 272), cov neeg mob yuav tsum tswj hwm tag nrho ntawm Chav Kawm 1 tab sis tsis ntau tshaj Class 2 ARV tshuaj nyob rau hauv lub hauv paus, thiab tsis tuaj yeem tsim qhov ARV lub hom phiaj los ntawm lawv cov tshuaj seem. Cov neeg mob no tau siv los ntawm kev sib piv ntawm 3: 1, thiab dig muag dig muag fostemsavir lossis placebo (n = 272) rau lawv cov kev kho mob tsis ua haujlwm tam sim no, thiab tau txais kev kho mob monotherapy rau 8 hnub. Cov neeg mob (n = 99) uas tsis muaj ib yam haujlwm tseem tshuav rau kev pom zoo los ntawm ARV raug tso rau hauv pawg neeg tsis muaj kev sib tham thiab tau txais daim ntawv lo qhib fostemsavir thiab kho kom zoo tom qab (OBT) nyob rau hnub 1. Lub ntsiab ntawm qhov kev tshawb fawb tau kev hloov pauv nruab nrab hauv log10 HIV-1 RNA ntawm kev sib koom tes ntawm nruab nrab hnub 1 txog rau hnub 8. Tom qab 8-hnub ua ob lub sijhawm dig muag, txhua tus neeg mob nyob hauv cov pab pawg neeg tau txais qhib daim ntawv fostemsavir thiab kho kom zoo tom qab. Cov haujlwm tseem ceeb kawg ua tiav nrog cov kav ntev ntawm cov lus teb ntawm 24, 48, thiab 96 lub lis piam, nrog rau kev hloov kev nyab xeeb los ntawm cov hauv paus hauv CD4+ cell technology thiab rov tshwm sim ntawm cov tshuaj tiv thaiv.

Cov txiaj ntsig pom tau hais tias raws qhov ntsuas qhov nce nruab nrab poob hauv HIV-1 RNA txij hnub 1 txog hnub 8 nyob rau hauv kev sib koom tes ntawm cov neeg sib koom tes, qhov kev soj ntsuam qhov kawg pom tias fostemsavir zoo dua rau cov placebo (txo qis 0.79 thiab 0.17 log10 c / mL, feem; p< 0.0001,="" nkag="" siab-rau-kho-tshwm="" sim="" [itt-e]="" cov="" pej="" xeem).="" hauv="" kev="" sib="" koom="" tes="" ntawm="" tus="" neeg,="" cov="" nqi="" tiv="" thaiv="" kev="" tiv="" thaiv="" kab="" mob="" thiab="" kev="" tiv="" thaiv="" lub="" cev="" tsis="" tu="" ncua="" tau="" nce="" ntxiv="" los="" ntawm="" 24="" lub="" lis="" piam="" mus="" rau="" 96="" lub="" lis="" piam="" hauv="" qhov="" no="" nyuaj-kho-multidrug="" resistant="" hiv-1="" tus="" neeg="">

Cov ntaub ntawv tshwj xeeb: Ntawm cov neeg mob kho nrog fostemsavir thiab kho kom zoo tom qab kho (OBT) hauv kev sib koom tes ua ke, cov uas tau ua tiav kev tiv thaiv kev tua kab mob (HIV-1 RNA< 40="" daim="" ntawv="" ml="" [c="" ml])="" ntawm="" 24,="" 48,="" thiab="" 96="" kev="" kho="" mob="" lub="" lis="" piam="" qhov="" feem="" ntawm="" cov="" neeg="" mob="" yog="" 53="" %,="" 54="" %,="" thiab="" 60="" %="" (n="163/272)." nrog="" lub="" sijhawm="" dhau="" los,="" cov="" neeg="" mob="" tau="" qhia="" txog="" kev="" txhim="" kho="" kev="" tiv="" thaiv="" tsis="" tu="" ncua,="" thiab="" qhov="" hloov="" pauv="" nruab="" nrab="" ntawm="" cd4+="" lub="" xov="" tooj="" tau="" txuas="" ntxiv="" nce="" (90,="" 139,="" thiab="" 205="" hlwb="" atl="" ntawm="" 24,="" 48,="" thiab="" 96="" lub="" lis="" piam="">

Hauv kev tshawb nrhiav, qhov tshwm sim tsis zoo tshaj plaws (≥5%, txhua qib) yog xeev ntuav thiab zawv plab. Los ntawm lub lim tiam 96th, qhov kev faib ua feem ntawm cov neeg mob uas tsis kho kev kho mob fostemsavir vim muaj cov xwm txheej tsis zoo yog 7% (randomized: 5%, tsis-randomized: 2%).