Ukwelashwa Okusha Kwe-Diabetic Retinopathy Ekhombisa Umphumela Omuhle

I-REGENXBIO Inc. imemezele idatha eyengeziwe yesikhashana enhle evela ocwaningweni oluqhubekayo lwe-Phase II ALTITUDE™ lwe-RGX-314 lokwelapha i-diabetic retinopathy (DR) ngaphandle kwe-centre-involved diabetic macular edema (CI-DME) isebenzisa ukulethwa kwe-suprachoroidal ehhovisi. Imininingwane yethulwa engqungqutheleni ye-Angiogenesis, Exudation, and Degeneration 2022 nguMichael A. Klufas, MD, Retina Service, Wills Eye Hospital, Umsizi kaProfessor we-Ophthalmology, Thomas Jefferson University. I-RGX-314 iphenywa njengendlela yokwelapha yofuzo yesikhathi esisodwa engaba khona yokwelapha ukuwohloka kwe-macular okuhlobene nobudala okumanzi kanye ne-DR.              

I-Study Design kanye nesibuyekezo sokuphepha esisuka ku-Phase II ALTITUDE Trial ye-RGX-314 yokwelashwa kwe-DR Ukusebenzisa i-Suprachoroidal Delivery

I-ALTITUDE iyisikhungo esiningi, ilebula evulekile, engahleliwe, elawulwayo yokwenyuka komthamo ohlola ukusebenza kahle, ukuphepha kanye nokubekezelelana kokulethwa kwe-suprachoroidal kwe-RGX-314 kusetshenziswa i-SCS Microinjector® ezigulini ezinokuxilongwa kwe-DR kwesifo sikashukela esibi kakhulu noma esibi esingenakuqhathaniswa. i-retinopathy (NPDR) noma i-mild proliferative diabetesic retinopathy (PDR). Iziguli ezingamashumi amabili ku-Cohort 1 zahlelwa ngokungahleliwe ukuze zithole i-RGX-314 ezingeni le-dose ye-2.5 × 1011 amakhophi e-genomic ngeso ngalinye (GC / iso) ngokumelene nokulawulwa kokubheka ngesilinganiso se-3: 1. I-Cohort 2 izofaka iziguli ze-20 ezingahleliwe ukuze zithole i-RGX-314 ezingeni elikhulayo le-dose ye-5 × 1011 GC / iso ngokumelene nokulawula kokubheka ku-3: isilinganiso se-1. I-Cohort 3 yakhelwe ukuhlola i-RGX-314 ezingeni lethamo elifanayo njenge-Cohort 2 ezigulini ezingama-20 ezine-neutralize antibody (NAb) positive. Ukubhaliswa kuyaqhubeka ku-Cohorts 2 kanye ne-3. Iziguli kulolu cwaningo azitholi ukwelashwa kwe-prophylactic immune suppressive corticosteroid ngaphambi noma ngemva kokuphathwa kwe-RGX-314.

Kusukela ngo-January 18, 2022, i-RGX-314 kubikwe ukuthi ibekezelelwe kahle ku-Cohort 1. Izigameko ezimbili ezimbi ezimbi zibikwe ezigulini ezimbili, zombili ezingabhekwa njengezihlobene nezidakamizwa. Phakathi kweziguli eziku-Cohort 1 ezifakwe umthamo we-RGX-314, akukho ukuvuvukala kwe-intraocular okubonwa. Njengoba kubikiwe ngaphambili, isiguli esisodwa sabhekana necala elincane le-episcleritis elaxazululwa nge-topical corticosteroids. Ukwelashwa kwe-ocular evamile kwavela izehlakalo ezimbi esweni locwaningo phakathi nezinyanga eziyisithupha azizange zithathwe njengezihlobene nezidakamizwa futhi zazimnene kakhulu. Lokhu kufaka phakathi ukopha kwe-conjunctival kanye ne-conjunctival hyperemia.

Isifinyezo Sedatha Yeqoqo 1 Ezinyangeni Eziyisithupha

Ezinyangeni eziyisithupha, ezigulini eziyi-15 ezinikezwe umthamo we-RGX-314 ku-Cohort 1, iziguli eziyisikhombisa (47%) zibonise ukuthuthukiswa okuzinyathelo ezimbili noma okukhulu kusukela kwesisekelo ku-Early Treatment Diabetic Retinopathy Study-Diabetic Retinopathy Severity Scale (DRSS), i isiphetho esiyinhloko socwaningo, uma kuqhathaniswa noziro weziguli ezinhlanu (0%) eqenjini lokulawula lokubuka. Isiguli esisodwa (7%) esinikezwe i-RGX-314 siyaqhubeka nokubonisa ukuthuthukiswa okunezinyathelo ezine. Iphesenti leziguli ze-Cohort 1 ezifakwe nge-RGX-314 ezizuza okungenani ukuthuthukiswa kwezinyathelo ezimbili ezinyangeni eziyisithupha kumehlo aphathwe i-RGX-314 (47%) lenyuke kusukela kumiphumela ebikiwe ngaphambilini yezinyanga ezintathu (33%). Ukuthuthukiswa okuzinyathelo ezimbili ku-DRSS kwamukelwe njengesiphetho esibalulekile yi-FDA ezinhlolweni zomtholampilo ze-DR.

Ezigulini eziyisikhombisa ezazine-NPDR (i-DR severity level 47-53) ekuqaleni, i-57% yeziguli ibonise ukuthuthukiswa okuzinyathelo ezimbili noma okukhulu kusukela ku-DRSS yokuqala ezinyangeni eziyisithupha ngemuva kokuphathwa kwe-RGX-314. Ezigulini eziyisishiyagalombili ezine-PDR (i-DR severity level ≥ 61) ekuqaleni, i-38% yeziguli ibonise ukuthuthukiswa okubili noma okukhulu ezinyangeni eziyisithupha ngemuva kokuphathwa kwe-RGX-314. 

Ezinyangeni eziyisithupha ngemva kokuphathwa kwe-RGX-314, iziguli ze-Cohort 1 zibonise ukuguqulwa kwesilinganiso esizinzile ku-BCVA yezinhlamvu ze-+0.3 uma kuqhathaniswa nesisekelo, kuyilapho iziguli ezinhlanu ezingalweni zokulawula ukuqaphela zibonisa ushintsho oluzinzile lwesilinganiso ku-BCVA yezinhlamvu ze-2.0 uma kuqhathaniswa nesisekelo.