Theem III lub luag haujlwm saib xyuas kev vam meej ntawm Akari ua kom tiav cov tshuaj tiv thaiv kev kho mob ntawm PNH

Akari Therapeutics tau tso tawm cov ntaub ntawv zoo ib ntus los ntawm Theem III CAPSTONE kawm txog C5 ua kom tiav cov tshuaj tiv thaiv kab mob rau hauv kev kho mob paroxysmal nocturnal hemoglobinuria (PNH).

Qhov no yog peb-ntu, ob-pab pawg, kev sib tw, qhib-daim ntawv lo tshawb kawm ua nyob rau hauv cov neeg mob nrog PNH uas yav dhau los tsis tau txais kev tiv thaiv inhibitor (kev kho mob thawj zaug) thiab yog nyob ntawm cov ntshav hloov. Hauv txoj kev tshawb nrhiav, cov neeg mob tau txais lub luag haujlwm thiab tau txais kev txhaj tshuaj niaj hnub ntawm nomacopan lossis kev saib xyuas tus qauv (SOC: ntshav hloov, anticoagulation lossis tsis siv tshuaj tiv thaiv) rau 6 lub hlis. Tom qab 6 lub hlis, cov neeg mob hauv SOC pawg tau txais nomacopan tau 3 lub hlis, thiab cov neeg mob hauv pab pawg nomacopan tseem tau txais nomacopan ntxiv txog peb hlis ntxiv. Qhov kawg ntawm qhov kev tshawb fawb yog: ruaj khov hemoglobin (Hb), txhais tau tias Hb qib siab tshaj li tus nqi tsim rau txhua tus neeg mob thaum lub sijhawm tshawb fawb ua ntej, thiab zam kom tsis txhob mob ntshav liab (PRBC) thaum lub sijhawm kho 6 lub hlis lub sijhawm. Txhua tus neeg mob yuav tau txais cov ntshav ntxiv yog tias Hb qis dua tus nqi teev tseg.

Cov ntaub ntawv tso tawm lub sijhawm no yog los ntawm thawj yim tus neeg mob uas tau nkag mus rau txoj kev tshawb no. Cov ntaub ntawv ib ntus qhia tau tias txhua tus neeg mob tau txais nomacopan mus txog qhov kawg ntawm kev hloov ntshav-ywj siab (piv txwv li tau txais kev tshem tawm cov ntshav): nyob rau thawj 6 lub hlis ntawm kev kho mob, 4 tus neeg mob uas tau muab rau nomacopan tsis tau txais ntshav ntxiv thiab tau raug xaiv los ua SOC Txhua 4 tus neeg mob tau txais kev txhaj ntshav. Ob pawg ntawm cov neeg mob muaj cov ntshav sib thooj keeb kwm zoo ib yam thiab txhais tau tias yog Hb kev teeb tsa, thiab kev sib txawv ntawm kev kho mob tau pom tseeb (p = 0.034).

Hauv Kev Tsum Ntu II COBALT PNH, 6 ntawm 8 tus neeg mob tau hloov ntshav-tos ua ntej kev kho mob. Tom qab 3 lub hlis ntawm kev kho mob, 3 ntawm 6 tus neeg mob tau tshem ntawm kev vam khom hloov ntshav, thiab seem 3 raug tshem tawm ntawm kev tshawb nrhiav kev soj ntsuam ntev txog kev nyab xeeb. Kev tso cov ntshav sib tos (txhais tias: tsis muaj ntshav ntxiv rau 6 lub hlis). Tshwj tsis yog rau ib tus neeg mob uas tau txais chav tsev ntawm PRBC nyob rau 12 lub hli dhau los, cov neeg mob tseem tshuav hloov ntshav-ywj pheej txog li ob xyoos.

Txog rau hnub no, tag nrho ntawm 14 PNH cov neeg mob tau raug kho nrog nomacopan hauv 4 qhov chaw sim tshuaj. Ntxiv Ntu III cov ntaub ntawv yuav tshaj tawm ntawm European Hematology (EHA) Kev Sib Tham Txhua Xyoo, Lub Rau Hli 11-14, 2020.

Kev sib tw kom zoo dua ntawm nomacopan (synergistic C5 thiab LTB4 inhibition)

Nomacopan yog ib qho me me protein (16740Da), uas yog soluble thiab ruaj khov. Nws ua ntawm kev ua kom tiav C5, uas tuaj yeem tiv thaiv kev tso tawm ntawm C5a thiab kev tsim C5b-9 (tseem hu ua membrane nres complex). Leukotriene B4 (LTB4). Ob C5 thiab LTB4 yog cov khoom tseem ceeb ntawm tib neeg lub cev tiv thaiv kab mob / tshuaj tiv thaiv. Nomacopan tau tsim kho rau kev kho mob los ntawm PNH, mob ntshav sabphigoid, atopic keratoconjunctivitis, thiab thrombotic microangiopathy.

Akari tab tom tsim qhov tshiab, chav-ntsuas kub-ruaj khov, siab-tsim nomacopan cov qauv tsim uas tso cai me me ntawm 0.3mL, txhaj qis-viscosity, siv cov koob txhaj zoo ib yam li insulin txhaj cwj mem, uas muab tshuaj subcutaneous ib zaug ib lub lim tiam. Kev cuv npe ntawm cov neeg mob nyob rau Theem III CAPSTONE txoj kev tshawb no tau ncua sij hawm tam sim no txhawm rau siv cov cai tshiab no.

Soliris yog blockbuster C5 ua kom tiav inhibitor tsim los ntawm Alexion. Nws tau tsim tawm xyoo 2007 thiab tau pom zoo los kho 4 yam mob uas tsis tshua pom zoo, suav nrog PNH. Cov tshuaj yog ib lub ntiaj teb zoo tshaj plaws kev muag tshuaj rau cov menyuam ntsuag, nrog muag $ 3.563 txhiab hauv xyoo 2018, thiab yog qhov tseeb "nyuj nyuj" rau Alexion. Tam sim no, lub tuam txhab tau txuas ntxiv tsim cov cim tshiab rau Soliris thiab tseem tab tom txhim kho kev kho dua tshiab ntawm Ultomiris, uas yog thawj zaug ua haujlwm ntev C5 ua kom tiav cov tshuaj tiv thaiv kom tau txais kev tswj hwm txhua txhua 8 lub lis piam thiab kuj tau pom zoo rau kev kho PNH.

Tam sim no, Soliris thiab Ultimiris tseem ntsib txoj kev sib tw muaj peev xwm los ntawm lwm qhov sib ntxiv inhibitors hauv PNH kev tsim kho kav dej. Ntxiv rau nomacopan, Apellis kuj tseem nyuam qhuav tshaj tawm cov qhabnias ntawm Ntu 3 lub taub hau-rau-lub taub hau PEGASUS kev kawm ntawm C3 ua kom muaj kev cuam tshuam inhibitor pegcetacoplan. Cov ntaub ntawv qhia tau tias pegcetacoplan yeej Soliris ntawm kev ua tau zoo. Hais txog qhov ua tau zoo ntawm qhov kawg, Hb-raug txhais nyob rau lub lim tiam 16 ntawm kev kho tau muaj qhov kev txhim kho tseem ceeb (+ 2.4g / dL vs -1.5g / dL; sib txawv = 3.8g / dL, p <> Cov txiaj ntsig tseem ceeb kuj tau pom nyob hauv qhov tseem ceeb hauv qab kawg: hauv lub lim tiam 16 ntawm kev kho, 85% ntawm cov neeg mob hauv pab pawg pegcetacoplan tsis muaj ntshav ntxiv, piv nrog 15% hauv pab pawg Soliris.