Imiphumela Emisha Yesivivinyo Ye-Gene Therapy Ye-Severe Hemophilia A

I-BioMarin Pharmaceutical Inc. namuhla imemezele ukushicilelwa kwemiphumela yocwaningo lweSigaba 3 GENEr8-1 lwe-valoctocogene roxaparvovec, ukwelapha ngofuzo oluphenyayo lokwelapha abantu abadala abane-hemophilia A enzima, ku-New England Journal of Medicine (NEJM). I-athikili enesihloko esithi, "Valoctocogene Roxaparvovec Gene Therapy for Hemophilia A," ibika unyaka owodwa noma ngaphezulu yedatha yokulandelela evela ocwaningweni futhi kubhekiselwa kuyo esihlokweni esishicilelwe kumagazini ofanayo we-Journal ivuma inzuzo engaba khona yokopha okuyiziro nokugwema. ukusetshenziswa kwe-prophylactic therapy.  

I-athikili yocwaningo yasekuqaleni ibika ukuthi ukulandela ukujova okukodwa kwabahlanganyeli be-valoctocogene roxaparvovec bahlangabezane namazinga okopha ancipha kakhulu ngonyaka, ukusetshenziswa kwe-factor VIII okuncishisiwe, kanye nomsebenzi we-factor VIII owandayo, kunangonyaka owandulela ukubhaliswa kocwaningo. Esibalweni esishiwo ngaphambili se-rollover esihlanganisa abahlanganyeli be-112 ababhalisele isifundo esingaba khona esingangeneleli, kusho ukusetshenziswa okugxilisiwe kwe-factor VIII yonyaka futhi kusho amazinga okopha aphathwayo ngemva kwesonto lesi-4 kwehle ukumnika ngemva kwe-99% kanye ne-84%, ngokulandelana (kokubili i-P <0.001) . Sekukonke, ababambiqhaza abangu-121/134 (90%) babengenako ukopha okulashiwe noma ukopha okumbalwa okulashiwe ngemva kokumnika, uma kuqhathaniswa ne-factor VIII prophylaxis njengoba kubhaliwe ocwaningweni olungangeneleli. Emasontweni angu-49-52, i-88% yabahlanganyeli inomsebenzi we-median factor VIII we-5 IU/dL noma ngaphezulu, njengoba kulinganiswa kusetshenziswa i-chromogenic substrate (CS) assay. 

“Ukopha ngokweqile kumelela umthwalo omkhulu wokulawulwa kwezifo kanye nesidingo esingafezeki sezokwelapha kubantu abaningi. Kuyangikhuthaza ukuthi ngonyaka wokuqala wokwelashwa, u-90% wabahlanganyeli bocwaningo babenokopha okungelashwanga noma ukopha okumbalwa okulashiwe ngemva kokumnika kune-factor VIII prophylaxis,” kusho uMargareth C. Ozelo, MD, PhD, uMqondisi, Hemocentro UNICAMP, Inyuvesi yaseCampinas kanye Nomphenyi Oyinhloko Wocwaningo Lwe-GENEr8-1. "Le miphumela ikhombisa amandla okulawula ukopha kwe-hemostatic okuqhubekayo ngalolu hlobo lokwelapha lwe-hemophilia A."

"Siyaziqhenya ngokuba ngamavulandlela ocwaningweni lokwelapha ngezakhi zofuzo ze-hemophilia A enzima kanye nokwabelana ngemininingwane yesiguli ngasinye esiza ukuqonda okuphelele kwesethi yedatha egcwele yalo muthi ongaguqula," kusho u-Hank Fuchs, MD, uMongameli Womhlaba Wonke. Ucwaningo Nokuthuthukiswa kwa-BioMarin. “I-Valoctocogene roxaparvovec icutshungulwe isikhathi eside kunanoma iyiphi enye indlela yokwelapha i-hemophilia A, futhi unyaka nonyaka, siyaqhubeka nokwandisa ulwazi lwethu lokuthi lokhu kwelashwa kophenyo kungase kuzuzise kanjani izimpilo zabantu abane-hemophilia A. Siyabonga kubahlanganyeli bocwaningo. nabaphenyi ngeqhaza labo elibalulekile kulolu hlelo lokuthuthukisa, oluhlanganisa i-GENEr8-1, ucwaningo olukhulu kakhulu lokwelapha ngezakhi zofuzo ku-hemophilia A.”

Ukuphepha kwe-Valoctocogene Roxaparvovec

Lolu ulwazi lwamanje kakhulu lokuphepha oluvela ekuhlaziyweni kweminyaka emibili yocwaningo lweSigaba 3 GENEr8-1 futhi luhlanganisa ukuphepha kukonke kwe-valoctocogene roxaparvovec. Ukuphepha okufakwe ekushicilelweni kwe-NEJM kusekelwe ekuhlaziyweni konyaka owodwa. Bonke ababambiqhaza ocwaningweni lweSigaba 3 bathola umthamo owodwa we-6e13 vg/kg. Abekho ababambiqhaza abathuthukise ama-inhibitors ku-Factor VIII, i-malignancy, noma izehlakalo ze-thromboembolic. Ngonyaka wesibili, azikho izimpawu zokuphepha ezintsha ezivele, futhi azikho izehlakalo ezimbi kakhulu ezihlobene nokwelashwa (SAE) ezibikiwe. Iziguli eziningi zaziyekile ukusebenzisa i-corticosteroid (CS) ngonyaka wokuqala, futhi kwakungekho ama-SAE ahlobene ne-CS ezigulini ezisele ezancishiswa ku-CS ngonyaka wesibili. Sekukonke, izehlakalo ezimbi ezivame kakhulu (AE) ezihlotshaniswa ne-valoctocogene roxaparvovec zenzeke kusenesikhathi futhi zihlanganisa ukusabela okuhlobene nokumnika kwesikhashana kanye nokukhuphuka okumaphakathi kuya kokumaphakathi kwama-enzyme esibindi angenazo ukulandelana komtholampilo okuhlala isikhathi eside. Ukuphakama kwe-Alanine aminotransferase (ALT) (abahlanganyeli abangu-119, i-89%), ukuhlolwa kwelabhorethri yokusebenza kwesibindi, kwahlala kuyi-AE evamile kakhulu. Ezinye izenzakalo ezimbi ezivamile kwakuyikhanda elibuhlungu (abahlanganyeli be-55, i-41%), i-arthralgia (abahlanganyeli abangu-53, i-40%), isicanucanu (abahlanganyeli abangu-51, 38%), ukuphakama kwe-aspartate aminotransferase (AST) (abahlanganyeli abangu-47, 35%), nokukhathala (40 ababambiqhaza, 30%). Ocwaningweni lweSigaba 1/2, i-SAE ye-salivary gland mass ikhonjwe kumhlanganyeli oyedwa wocwaningo, owalashwa eminyakeni engaphezu kwemihlanu edlule, futhi kwabikwa ukuthi ayihlobene ne-valoctocogene roxaparvovec ngumseshi. Iziphathimandla zezempilo ezifanele zaziswe ngasekupheleni kuka-2021, futhi zonke izifundo zisaqhubeka ngaphandle kokuguqulwa. I-Data Monitoring Committee ezimele (DMC) iqhubekile yabuyekeza icala. Ukuhlaziywa kwe-genomic kwenziwa njengoba kushiwo kuphrothokholi yesilingo somtholampilo. 

GENER8-1 Incazelo Yocwaningo

Ucwaningo lomhlaba wonke lweSigaba sesi-3 GENEr8-1 luwucwaningo lwengalo eyodwa, olunelebula evulekile oluhlola ukusebenza kahle nokuphepha kwe-valoctocogene roxaparvovec kubantu abane-hemophilia A (FVIII ≤ 1 IU/dL) ababelashwe ngokuqhubekayo nge-prophylactic exogenous factor VIII. okungenani unyaka owodwa ngaphambi kokubhalisa. Ukuphela kokusebenza okuyinhloko kwaba ukuguqulwa kusukela kusisekelo somsebenzi we-Factor VIII (i-CS assay) emavikini angu-49-52 ngemva kokumnika. Iziphetho zokuphumelela kwesibili zazihlanganisa ushintsho olusuka kusisekelo ekusetshenzisweni kwaminyaka yonke kwe-factor VIII concentrate kanye nenani lonyaka leziqephu zokuphuma kwegazi ngemva kweviki 4. Ukuphepha kwahlolwa ngokurekhoda izenzakalo ezimbi, ukuhlolwa kwelabhorethri, nokuhlolwa ngokomzimba. Sebebonke, isamba sabahlanganyeli be-134 bathole ukumnika okukodwa kwe-valoctocogene roxaparvovec ngedosi ye-6e13 vg/kg, futhi bonke ababambiqhaza babenezinyanga eziyi-12 zokulandelela okungenani ngesikhathi sokunqunywa kwedatha. Ababambiqhaza bokuqala abangama-22 babhaliswe ngokuqondile ocwaningweni lweSigaba sesi-3, abayi-17 kubo ababengenayo i-HIV futhi banikwa umthamo okungenani iminyaka emi-2 ngaphambi kosuku lokunqunywa kwedatha. Ababambiqhaza abangu-112 abasele (isibalo sabantu abathintekayo) baqede okungenani izinyanga eziyisithupha ocwaningweni oluhlukile olungangeneleli ukuze bahlole ngokuzayo iziqephu zokopha, ukusetshenziswa kwe-factor VIII, kanye nezinga lempilo elihlobene nempilo ngenkathi bethola i-factor VIII prophylaxis ngaphambi kokugingqika nokuthola eyodwa. ukufakwa kwe-valoctocogene roxaparvovec ocwaningweni lwe-GENEr8-1.