I-Protalix BioTherapeutics, Inc. namhlanje ibhengeze iziphumo zokugqibela ezivela kwi-BRIGHT Phase III yolingo lwezonyango oluvavanya i-pegunigalsidase alfa (PRX 102) yonyango olunokubakho lwe-Fabry isifo. Iziphumo zibonisa ukuba unyango kunye ne-2 mg / kg ye-PRX-102 elawulwa yi-intravenous (IV) infusion nganye kwiiveki ezine yayinyamezeleke kakuhle, kwaye isifo se-Fabry sihlolwe ngokuqikelelwa kwe-glomerular filtration rate (eGFR) i-slope kunye ne-plasma lyso-Gb3 concentration yayizinzile.
"Siyavuya ukwabelana ngedatha yokugqibela kwisifundo se-BRIGHT, isiganeko esibalulekileyo kwinkqubela phambili yenkqubo yethu yekliniki ye-PRX-102," kusho uDror Bashan, uMongameli weProtalix kunye neGosa eliLawulayo eliyiNtloko. “Ubukho bale datha ukuze iqwalaselwe kwakhona yi-US Food and Drug Administration, i-Arhente yaMayeza yaseYurophu kunye nabanye abalawuli lelinye inyathelo eliya phambili ekuvunyweni okulindelweyo kwe-PRX-102 njengenye indlela elungileyo enokubakho kwizigulana zabantu abadala beFabry kuzo zombini i-1 mg eqhelekileyo. \kg rhoqo kwiiveki ezimbini kunye ne-2 mg\kg rhoqo kwiiveki ezine."
I-PRX-102 isityalo esine-cell-expressed recombinant, i-PEGylated, i-cross-linked α galactosidase Umviwa wemveliso. I-BRIGHT Phase III yolingo lwekliniki (i-NCT03180840) yayiyi-multicenter, i-open-label yamazwe ngamazwe, i-switch-over study eyenzelwe ukuvavanya ukhuseleko, ukusebenza kakuhle kunye ne-pharmacokinetics yonyango kunye ne-2 mg / kg ye-PRX-102 elawulwa rhoqo kwiiveki ezine kwiiveki ze-52. Iyonke i-14 infusions). Uphononongo lubhalise izigulane ze-30 zabantu abadala abanesifo se-Fabry (amadoda angama-24 kunye nabasetyhini be-6) abanentsingiselo (SD) yobudala be-40.5 (11.3) iminyaka, ukusuka kwi-19 ukuya kwi-58 iminyaka, abaye bafumana unyango lokutshintshwa kwe-enzyme evunyiweyo (ERT) ubuncinane. iminyaka emithathu kwidosi ezinzileyo elawulwa rhoqo kwiiveki ezimbini (i-agalsidase alfa – Replagal® okanye i-agalsidase beta – Fabrazyme®). Ezona mpawu zixhaphakileyo zesifo seFabry kwisiseko yi-acroparesthesia, ukunganyamezeli ubushushu, i-angiokeratomas kunye ne-hypohydrosis.
Zonke izigulane ezithathe inxaxheba kuphononongo zifumene ubuncinane idosi enye ye-PRX-102, kunye nezigulane ze-29 zagqiba isifundo. Kwezi zigulane ze-29, i-28 ifumene i-regimen ejoliswe kwi-2 mg / kg ye-PRX-102 rhoqo kwiiveki ezine kulo lonke uphononongo, ngelixa esinye isigulane satshintshelwa kwi-1 mg / kg ye-PRX-102 rhoqo kwiiveki ezimbini ngeprotocol kwi-11th infusion. . Esinye isigulana sarhoxa kwisifundo emva kokungena okokuqala ngenxa yengozi yendlela.
I-infusions yokuqala ye-PRX-102 ilawulwa phantsi kweemeko ezilawulwayo kwindawo yophando. Ngokusekelwe kwiikhrayitheriya ezichazwe kwangaphambili kwiprotocol yokufunda, izigulane ziye zakwazi ukufumana i-PRX-102 infusions kwi-setup yokunyamekela ekhaya emva kokuba uMphenyi kunye noMxhasi weMonitor wezoNyango bavumile ukuba kukhuselekile ukwenza njalo.
Ngokubanzi, i-33 ye-182 iyonke iziganeko ezimbi ezibangelwa unyango (TEAEs) zichazwe kwizigulane ezisithoba (30.0%) zithathwa njengezinto ezinxulumene nonyango; zonke zazinobulali okanye ziphakathi ngobungqongqo kwaye uninzi lwasombululwa ekupheleni kophononongo. Kwakungekho zi-TEAE ezinzulu okanye eziqatha ezinxulumene nonyango kwaye akukho zi-TEAE ezikhokelele ekufeni okanye ekurhoxisweni kofundo. Kwii-TEAEs ezinxulumene nonyango, i-27 yayiyi-infusion-related reactions (IRRs) kwaye intsalela yayizehlo zorhudo, i-erythema, ukukhathala, ukugula okufana nomkhuhlane, ukunyuka kweprotheni yomchamo / umlinganiselo we-creatinine, kunye nomchamo ochanekileyo kwiiseli ezimhlophe zegazi. Ii-IRR ezingama-27 zichazwe kwizigulane ezihlanu (16.7%), zonke zingamadoda. Zonke ii-IRR zenzeke ngexesha lokunyuswa okanye kwiiyure ezimbini emva kokufakwa; akukho ziganeko zirekhodwe phakathi kweeyure ezimbini kunye ne-24 emva kwe-infusion. Akukho nasinye kwizigulane ezingenazo i-anti-drug antibodies (ADAs) ekuhlolweni eziphuhliswe ii-ADA ezenziwe ngonyango emva kokutshintshela kunyango lwe-PRX-102.
Imilinganiselo yeziphumo zokufunda ibonisa ukuba i-plasma lyso Gb3 igxininiso yahlala izinzile ngexesha lokufunda kunye noshintsho oluqhelekileyo (±SE) lwe-3.01 nM (0.94) ukusuka kwisiseko (19.36 nM ± 3.35) ukuya kwiVeki ye-52 (22.23 ± 3.60 nM). Kuthetha ukuba ixabiso elipheleleyo le-eGFR lizinzile ngexesha le-52 yeveki yonyango, kunye noshintsho oluqhelekileyo ukusuka kwisiseko se-1.27 mL / min / 1.73 m2 (1.39). I-Mean (SE) i-eGFR slope, ekupheleni kophononongo, kuluntu lonke, i-2.92 (1.05) mL / min / 1.73m2 / ngonyaka ebonisa ukuzinza.
"Siyavuya ukwazisa iziphumo zokugqibela ezivela kwi-BRIGHT Phase III yolingo lwezonyango kwaye singathanda ukubulela abaphandi bophononongo, izigulane zesifo se-Fabry, kunye neentsapho zabo ezinikezele ixesha labo kunye neenzame kolu phando lubalulekileyo," watsho uGiacomo Chiesi, intloko yeChiesi. Global Rare Diseases. Ngokusekwe kule datha kunye nezifundo ezongezelelweyo zeklinikhi, sikholelwa ukuba i-PRX-102 inokuba lukhetho olutsha olubalulekileyo lonyango kwizigulana ezifumana infusions ye-ERT rhoqo emva kweeveki ezimbini, kwaye sijonge phambili ekuqhubeleni phambili umsebenzi wethu kwihlabathi jikelele ukufumana imvume yolawulo njengoko ngokukhawuleza kangangoko kunokwenzeka kwaye unikeze ukufikelela kuluntu lwesifo saseFabry. ”
INTO ONOKUYITHATHA KWELI NQAKU:
- Food and Drug Administration, the European Medicines Agency and other regulators is another step forward towards the anticipated approval of PRX-102 as a potential good alternative for adult Fabry patients in both the regular 1 mg\kg every two weeks as well as the 2 mg\kg every four weeks regimen.
- Of these 29 patients, 28 received the intended regimen of 2 mg/kg of PRX-102 every four weeks throughout the entire study, while one patient was switched to 1 mg/kg of PRX-102 every two weeks per protocol at the 11th infusion.
- The BRIGHT Phase III clinical trial (NCT03180840) was a multicenter, multinational open-label, switch-over study designed to evaluate the safety, efficacy and pharmacokinetics of treatment with 2 mg/kg of PRX-102 administered every four weeks for 52 weeks (a total of 14 infusions).
