Unyango olutsha lwe-Diabetic Retinopathy ebonisa isiphumo esihle

I-REGENXBIO Inc. ibhengeze idatha eyongezelelweyo yesikhashana evela kwiSigaba se-II ALTITUDE™ solingo lwe-RGX-314 yonyango lwe-diabetic retinopathy (DR) ngaphandle kwe-diabetic macular edema (CI-DME) ebandakanyekayo kwi-ofisi yokuhanjiswa kwe-suprachoroidal. Idatha inikezelwa kwinkomfa ye-Angiogenesis, Exudation, kunye ne-Degeneration 2022 nguMichael A. Klufas, MD, iNkonzo yeRetina, iSibhedlele se-Will Eye, uNjingalwazi oNcedisayo we-Ophthalmology, iYunivesithi yaseThomas Jefferson. I-RGX-314 iphandwa njengonyango olunokubakho lwexesha elilodwa lonyango lwe-macular degeneration emanzi kunye ne-DR.              

UYilo loFundo kunye noHlaziyo loKhuseleko kwiSigaba sesi-II i-ALTITUDE yovavanyo lwe-RGX-314 yoNyango lwe-DR usebenzisa i-Suprachoroidal Delivery

I-ALTITUDE yi-multi-center, i-open-label, i-randomized, i-controlled ye-dose-escalation trial evavanya ukuphumelela, ukhuseleko kunye nokunyamezela kokunikezelwa kwe-suprachoroidal ye-RGX-314 usebenzisa i-SCS Microinjector® kwizigulane ezine-DR yokuxilongwa kwesifo seswekile esinobunzima okanye esibi. i-retinopathy (NPDR) okanye i-mild proliferative diabetic retinopathy (PDR). Izigulane ezingamashumi amabini kwi-Cohort 1 zazingenamkhethe ukufumana i-RGX-314 kwinqanaba le-dose ye-2.5 × 1011 iikopi ze-genomic ngeso ngalinye (GC / iso) ngokubhekiselele kulawulo lokujonga kwi-3: umlinganiselo we-1. Iqela le-2 liya kubandakanya izigulane ze-20 ezingahleliweyo ukufumana i-RGX-314 kwinqanaba lokunyuka kwe-dose ye-5 × 1011 GC / iliso ngokubhekiselele kulawulo lokuqwalasela kwi-3: umlinganiselo we-1. Iqela le-3 lenzelwe ukuvavanya i-RGX-314 kwinqanaba elifanayo ledosi njenge-Cohort 2 kwizigulane ze-20 ezingenayo i-antibody (NAb) engathathi hlangothi. Ukubhaliswa kuyaqhubeka kwi-Cohorts 2 kunye ne-3. Izigulane kolu vavanyo alufumani unyango lwe-prophylactic immune suppressive corticosteroid ngaphambi okanye emva kokulawulwa kwe-RGX-314.

Ukususela ngoJanuwari 18, i-2022, i-RGX-314 yaxelwa ukuba inyamezeleke kakuhle kwi-Cohort 1. Iziganeko ezimbi ezimbi ezimbi zichazwe kwizigulane ezimbini, zombini ezo zingaqwalaselwanga ezinxulumene neziyobisi. Phakathi kwezigulana ezikwi-Cohort 1 ezifakwe kwi-RGX-314, akukho ukudumba kwe-intraocular kwabonwa. Njengoko bekuxeliwe ngaphambili, esinye isigulana safumana imeko encinci ye-episcleritis eyasonjululwa nge-topical corticosteroids. Unyango lwe-ocular oluqhelekileyo oluvela kwiziganeko ezimbi kwiliso lophononongo ukuya kwiinyanga ezintandathu azizange zithathelwe ingqalelo ezinxulumene neziyobisi kwaye bezinobulali. Ezi ziquka ukopha kwe-conjunctival kunye ne-conjunctival hyperemia.

Isishwankathelo seDatha yeQela loku-1 kwiinyanga ezintandathu

Kwiinyanga ezintandathu, kwizigulane ze-15 ezifakwe kwi-RGX-314 kwi-Cohort 1, izigulane ezisixhenxe (47%) zibonise ukuphuculwa kwamanyathelo amabini okanye ngaphezulu ukusuka kwisiseko kwi-Early Treatment Diabetic Retinopathy Study-Diabetic Retinopathy Severity Scale (DRSS), i Isiphelo sokuqala sophononongo, xa kuthelekiswa ne-zero yezigulane ezihlanu (0%) kwiqela lolawulo lokujonga. Isigulane esinye (7%) esifakwe kwi-RGX-314 siyaqhubeka nokubonisa ukuphuculwa kwamanyathelo amane. Ipesenti yezigulane ze-Cohort 1 ezifakwe kwi-RGX-314 zifezekisa ubuncinane ukuphuculwa kwamanyathelo amabini kwiinyanga ezintandathu kwi-RGX-314 yamehlo aphathwayo (47%) yanda ukusuka kwiziphumo ezixelwe ngaphambili zeenyanga ezintathu (33%). Uphuculo olunamanyathelo ama-2 kwi-DRSS yamkelwe njengesiphelo esibalulekileyo yi-FDA kulingo lwezonyango lwe-DR.

Kwizigulane ezisixhenxe ezine-NPDR (i-DR yobunzima bezinga le-47-53) kwisiseko, i-57% yezigulane zibonise ukuphuculwa kwamanyathelo amabini okanye ngaphezulu ukusuka kwisiseko se-DRSS kwiinyanga ezintandathu emva kokulawulwa kwe-RGX-314. Kwizigulane ezisibhozo ezine-PDR (inqanaba lobunzima be-DR ≥ 61) kwisiseko, i-38% yezigulane zibonise ukuphuculwa kwamanyathelo amabini okanye ngaphezulu kwiinyanga ezintandathu emva kokulawulwa kwe-RGX-314. 

Kwiinyanga ezintandathu emva kokulawulwa kwe-RGX-314, izigulane ze-Cohort ze-1 zibonise utshintsho oluzinzile kwi-BCVA ye-+0.3 iileta xa kuthelekiswa nesiseko, ngelixa izigulane ezihlanu kwingalo yokulawula ukujonga zibonise utshintsho oluzinzile kwi-BCVA ye-2.0 iileta xa kuthelekiswa nesiseko.