Lub Cim Txhab Tshiab Ntawm Qhov Ncauj PI3Kδ / CK1-ε Dual Tus Txhuam Hniav Ukoniq Tau Pom Zoo Los Ntawm Asmeskas FDA!

TG Kev Kho Mob yog lub tuam txhab biopharmaceutical ua kom muaj kev tsim kho tshiab rau cov neeg mob uas muaj cov kab mob B cell-mediated. Tsis ntev los no, lub tuam txhab tshaj tawm tias Asmeskas Chaw Tswj Xyuas Khoom Noj thiab Tshuaj (FDA) tau ua kom muaj kev pom zoo los ntawm Ukoniq (umbralisib, 200mg ntsiav tshuaj) rau kev kho mob: (1) tau txais tsawg kawg ib qho kev rov tshwm sim lossis rov ua dua tshiab raws li los tiv thaiv CD20 cov neeg mob uas muaj marginal. cheeb tsam lymphoma (MZL); (2) Cov neeg laus uas muaj mob rov huam lossis rov huam dua qub los ntawm refluory follicular lymphoma (FL) uas tau txais tsawg kawg yog 3 cov kab ke kho mob Hais txog kev noj tshuaj, lub koob tshuaj pom zoo ntawm Ukoniq yog 800mg (4 ntsiav tshuaj), noj ib hnub ib zaug noj ntawm qhov ncauj nrog zaub mov.

Nws tsim nyog teev tias Ukoniq yog thawj zaug thiab tsuas yog hais qhov ncauj, ib zaug ib hnub, phosphoinositide-3-kinase δ (PI3K-δ) thiab casein kinase 1 tau pom zoo los kho kev mob rov qab / refractory MZL thiab FL. -ε (CK1-ε) dual inhibitor. Raws li tus lej teb tag nrho (ORR) cov ntaub ntawv los ntawm Theem 2 UNITY-NHL kev sim (NCT02793583), Ukoniq tau txais kev pom zoo nrawm dua. Kev tso cai txuas ntxiv rau cov ntsuas no yuav yog los ntawm kev txheeb xyuas qhov tseeb thiab qhov piav qhia txog cov txiaj ntsig tau zoo hauv cov kev sim kuaj pom. Ntawm 2 qhov ntsuas, MZL qhov taw qhia tau tso cai kev kuaj xyuas thawj zaug. Ib qho ntxiv, Ukoniq tau yav tas los tso cai rau Breakthrough Drug Designation (BTD) rau kev kho MZL thiab Chaw Kho Mob Yeeb Tshuaj Kho Mob (ODD) rau kev kho MZL thiab FL

Michael S. Weiss, Tus Thawj Coj ntawm Executive thiab CEO ntawm TG Cov Kws Kho Mob, hais tias:" Ukoniq' s kev pom zoo hnub no yog hnub keeb kwm rau peb lub tuam txhab. Nov yog thawj qhov kev pom zoo uas peb tau txais. Peb zoo siab heev uas tuaj yeem koom ua ke tshiab PI3K-δ thiab CK1-ε inhibitors coj cov mob rov huam tuaj / tawm kho MZL thiab FL cov neeg mob."

Dr. Nathan Fowler, tus kws tshawb fawb lub rooj zaum ntawm MZL& FL cohort ntawm UNITY-NHL txoj kev kawm thiab cov xibfwb ntawm cov tshuaj ntawm University of Texas MD Anderson Cancer Center, hais tias:" Txawm hais tias kev nce qib hauv kev kho mob, MZL thiab FL yog cov tseem kho tsis tau cov kab mob. Rau cov neeg mob uas rov zoo li qub tom qab kev kho mob dhau los Cov kev kho mob muaj qhov txwv thiab tsis muaj tus txheej txheem kev tswj kom zoo. Nrog kev pom zoo ntawm umbralisib, tam sim no peb muaj lub hom phiaj, lub qhov ncauj, ib zaug ib hnub, muab cov neeg mob nrog txoj kev kho mob tshiab, thiab tseem yuav los tawm tsam cov kab mob no ua rau muaj kev cia siab tshiab."

Qhov pom zoo no yog txiav txim siab raws li cov ntaub ntawv los ntawm ob txoj kev sib koom tes ua ke hauv UNITY-NHL Theem 2b sim. UNITY-NHL yog qhov chaw ntau ntau, qhib-daim ntawv lo theem 2b kawm. Ob txoj kev sib koom tes tshuaj ntsuam xyuas Ukoniq li kev ntsuas tshuaj rau 69 cov neeg mob uas rov mob / tso tawm MZL (yav dhau los tau txais tsawg kawg ib txoj kev kho, suav nrog kev tiv thaiv CD20 raws li kev cai), 117 cov neeg mob uas tau rov mob / rov ua dua tshiab FL (yav dhau los tau txais tsawg kawg 2 kev kho mob, nrog rau cov tshuaj tiv thaiv. -CD20 monoclonal antibody thiab ib tus neeg sawv cev alkylating). Txhua pawg neeg sib koom tes nce mus txog nws qhov kawg ntawm cov lus teb tag nrho (ORR) thiab mus txog 40-50% lub hom phiaj cov tswv yim kev qhia tau lees paub los ntawm Independent Review Committee (IRC).

Cov ntaub ntawv los ntawm MZL cohort tau qhia tias ORR yog 49%, ntawm cov lus teb tiav (CR) yog 16%, feem ntawm tus lej teb (PR) yog 33%, thiab nruab nrab lub sijhawm ntawm teb (DOR) tseem tsis tau mus txog. FL cov ntaub ntawv qhia pom: ORR yog 43%, uas CR yog 3.4%, PR yog 39%, thiab nruab nrab DOR yog 11,1 hli. Hauv txoj kev tshawb fawb, Ukoniq tau pom zoo zoo thiab muaj kev nyab xeeb.

Cov tshuaj ua ntu zus ntawm Ukoniq yog umbralisib, uas yog qhov ncauj qhov ncauj, ib zaug ob zaug ua rau muaj kev cuam tshuam cov PI3Kδ thiab CK1-ε, uas yuav ua rau nws kov yeej qee qhov teeb meem thev cuam tshuam nrog thawj tiam ntawm PI3Kδ inhibitors. Phosphatidylinositol-3 kinase (PI3K) yog chav kawm ntawm cov enzymes koom nrog kev nthuav tawm ntawm tes thiab kev muaj sia nyob, kev sib txawv ntawm tes, kev thauj mus los, thiab kev tiv thaiv kab mob. PI3K muaj plaub lub subtypes (α, β, δ, thiab γ), cov uas ty subtype yog qhia muaj nyob rau hauv cov hlwb hematopoietic keeb kwm thiab feem ntau cuam tshuam nrog B-cell-txuam lymphoma.

Umbrasib muaj nanomolar potency rau raws subtype ntawm PI3K, thiab muaj kev xaiv siab rau alpha, beta, thiab gamma subtypes. Umbralisib kuj tseem ceeb tshwj xeeb ua rau casein kinase 1-ε (CK1-ε), uas tej zaum yuav muaj qhov cuam tshuam los tiv thaiv tus mob qog nqaij hlav, thiab tseem yuav hloov kho T cell ua si cuam tshuam nrog kev tiv thaiv kab mob tsis zoo uas pom nyob hauv PI3K inhibitors yav dhau los.

Cov PI3Kδ pom zoo tam sim no cuam tshuam txog kev tiv thaiv autoimmune-mediated toxicity, xws li lub siab ua rau lub siab, mob ntsws, thiab mob plab. Piv nrog kev pom zoo PI3K inhibitors, tus kab mob hloov pauv ntawm umbralisib' s tshwj xeeb sib txawv, nws qhov tshwj xeeb cuam tshuam rau CK1-ε, thiab nws cov cim tshwj xeeb thiab cov ntawv pov thawj tshuaj lom neeg yuav muaj cov yam ntxwv sib txawv hauv PI3K inhibitor chav kawm.

Umbralisib tau ua pov thawj nws cov haujlwm hauv cov qauv preclinical thiab cov kev tshawb fawb soj ntsuam ntawm hematological malignancies. Tam sim no, Theem IIb thiab Theem III sim hauv CLL thiab NHL cov neeg mob tseem niaj hnub soj ntsuam kev kho tus mob hlab ntaws plab.

Ntxiv nrog rau umbralisib, TG tseem tab tom txhim kho cov tshuaj monoclonal antibody ublituximab (TG-1101), uas yog glycoengineered chimeric IgG1 monoclonal antibody tsom CD20. Tam sim no nyob rau theem III kev soj ntsuam kev loj hlob los soj ntsuam kev kho mob qog noj ntshav. (Mob ntsws lymphocytic mus ntev [CLL], tsis muaj Hodgkin's lymphoma [NHL]) thiab tsis mob khees-xaws (ntau myeloma [MM]).

Ntxiv rau, TG muaj ntau lub cuab tam uas tau nkag mus rau theem I kev soj ntsuam, nrog rau PD-L1 monoclonal antibody TG-1501, covalently khi Bruton' s tyrosine kinase (BTK) inhibitor TG-1701, thiab lwm yam.