Liphetho tse Nchafalitsoeng tsa Tleliniki mabapi le Phekolo ea Mafu a Fabry

Protalix BioTherapeutics, Inc. kajeno e phatlalalitse liphetho tsa ho qetela ho tsoa tekong ea kliniki ea BRIGHT Phase III e hlahlobang pegunigalsidase alfa (PRX 102) bakeng sa phekolo e ka bang teng ea lefu la Fabry. Liphello li bontša hore phekolo e nang le 2 mg / kg ea PRX-102 e tsamaisoang ke intravenous (IV) ka mor'a libeke tse ling le tse ling tse 'nè e ne e mamelloa hantle,' me lefu la Fabry le hlahlojoa ka tekanyo e hakantsoeng ea glomerular filtration rate (eGFR) le plasma lyso-Gb3 concentration e ne e tsitsitse.  

"Re thabetse ho arolelana lintlha tsa ho qetela tse tsoang thutong ea BRIGHT, mohato oa bohlokoa tsoelo-peleng ea lenaneo la rona la bongaka la PRX-102," ho boletse Dror Bashan, Mopresidente oa Protalix le Ofisiri e ka Sehloohong ea Phethahatso. "Boteng ba lintlha tsena bakeng sa ho hlahlojoa ke Tsamaiso ea Lijo le Lithethefatsi ea US, Setsi sa Meriana sa Europe le balaoli ba bang ke mohato o mong oa ho ea pele ho tumello e lebelletsoeng ea PRX-102 e le khetho e ntle bakeng sa bakuli ba batho ba baholo ba Fabry ho 1 mg e tloaelehileng. \kg libeke tse ling le tse ling tse peli hammoho le 2 mg\kg libeke tse ling le tse ling tse nne.

PRX-102 ke semela se hlahisoang ke lisele, PEGylated, cross-linked α galactosidase A sehlahisoa sa sehlahisoa. Teko ea kliniki ea BRIGHT Phase III (NCT03180840) e ne e le thuto e bulehileng ea linaha tse ngata, e bulehileng, e etselitsoeng ho hlahloba tšireletso, katleho le pharmacokinetics ea phekolo ka 2 mg / kg ea PRX-102 e tsamaisoang libeke tse ling le tse ling tse 'nè bakeng sa libeke tsa 52. kakaretso ea li-infusions tse 14). Boithuto bo ngolisitse bakuli ba baholo ba 30 ba nang le lefu la Fabry (banna ba 24 le basali ba 6) ba nang le lilemo tse bolelang (SD) tsa lilemo tse 40.5 (11.3), ho tloha 19 ho isa ho lilemo tse 58, bao pele ba ileng ba amohela kalafo e ncha ea enzyme (ERT) bonyane. lilemo tse tharo ka tekanyo e tsitsitseng e tsamaisoang libeke tse ling le tse ling tse peli (agalsidase alfa - Replagal® kapa agalsidase beta - Fabrazyme®). Matšoao a tloaelehileng a lefu la Fabry qalong e ne e le acroparesthesia, ho se mamelle mocheso, angiokeratomas le hypohydrosis.

Bakuli bohle ba kentseng letsoho thutong ba fumane bonyane tekanyo e le 'ngoe ea PRX-102, mme bakuli ba 29 ba qetile thuto. Ho bakuli bana ba 29, 28 e ile ea fumana mokhoa o reriloeng oa 2 mg / kg ea PRX-102 libeke tse ling le tse ling tse 'nè ho pholletsa le thuto eohle, ha mokuli a le mong a fetisetsoa ho 1 mg / kg ea PRX-102 libeke tse ling le tse ling tse peli ka protocol ho 11th infusion. . Mokuli e mong o ile a ikhula thutong ka mor'a ho kenngoa ha pele ka lebaka la kotsi ea sephethephethe.

Li-infusions tsa pele tsa PRX-102 li ne li tsamaisoa tlas'a maemo a laoloang sebakeng sa lipatlisiso. Ho latela mekhoa e boletsoeng esale pele ho protocol ea thuto, bakuli ba ile ba khona ho fumana infusions ea bona ea PRX-102 setsing sa tlhokomelo ea lapeng hang ha Mofuputsi le Sponsor Medical Monitor ba lumetse hore ho bolokehile ho etsa joalo.

Ka kakaretso, 33 ea 182 kakaretso ea liketsahalo tse mpe tse hlahang kalafo (TEAEs) tse tlalehiloeng ho bakuli ba robong (30.0%) li ne li nkoa li amana le phekolo; kaofela li ne li le bonolo kapa li itekanetse ka matla 'me bongata bo ile ba rarolloa qetellong ea thuto. Ho ne ho se na li-TEAE tse tebileng kapa tse matla tse amanang le kalafo 'me ha ho li-TEAE tse lebisitseng lefung kapa ho tlohela thuto. Har'a li-TEAE tse amanang le phekolo, tse 27 e ne e le li-infusion-related reactions (IRRs) 'me tse setseng e ne e le liketsahalo tse le' ngoe tsa letšollo, erythema, mokhathala, mafu a kang a ntaramane, ho eketseha ha moroto oa protheine / creatinine, le moroto o nepahetseng bakeng sa lisele tse tšoeu tsa mali. Li-IRR tse 27 li tlalehiloe ho bakuli ba bahlano (16.7%), kaofela e le banna. Li-IRR kaofela li etsahetse nakong ea infusion kapa ka mor'a lihora tse peli ka mor'a ho kenngoa; ha ho liketsahalo tse tlalehiloeng pakeng tsa lihora tse peli le 24 ka mor'a infusion. Ha ho le ea mong oa bakuli ba se nang li-anti-drug antibodies (ADAs) ha ho hlahlojoa ba hlahisitseng li-ADA tse susumelitsoeng ke kalafo ka mor'a ho fetohela kalafo ea PRX-102.

Mehato ea sephetho sa thuto e bontša hore likhahla tsa plasma lyso Gb3 li ile tsa lula li tsitsitse nakong ea thuto ka phetoho e bolelang (±SE) ea 3.01 nM (0.94) ho tloha qalong (19.36 nM ± 3.35) ho ea ho Beke ea 52 (22.23 ± 3.60 nM). Ho bolela litekanyetso tse feletseng tsa eGFR li ne li tsitsitse nakong ea phekolo ea libeke tsa 52, ka phetoho e bolelang ho tloha motheong oa 1.27 mL / min / 1.73 m2 (1.39). Ho bolela (SE) eGFR letsoapo, qetellong ea thuto, bakeng sa baahi bohle, e ne e le 2.92 (1.05) mL / min / 1.73m2 / selemo e bontšang botsitso.

"Re thabetse ho phatlalatsa liphetho tsa ho qetela tsa teko ea kliniki ea BRIGHT Phase III 'me re rata ho leboha bafuputsi ba thuto, bakuli ba lefu la Fabry, le malapa a bona ba faneng ka nako le boiteko ba bona ho etsa lipatlisiso tsena tsa bohlokoa," ho boletse Giacomo Chiesi, hlooho ea Chiesi. Mafu a Rarehang a Lefatše Lohle. "Ho ipapisitsoe le lintlha tsena le lithuto tsa tlatsetso tsa bongaka, re lumela hore PRX-102 e kanna ea ba khetho ea bohlokoa e ncha ea kalafo bakeng sa bakuli ba ntseng ba amohela infusions ea ERT kamora libeke tse ling le tse ling tse peli, 'me re labalabela ho ntšetsa pele mosebetsi oa rona lefats'eng ka bophara ho fumana tumello ea taolo joalo ka kapele kamoo ho ka khonehang le ho fana ka phihlello sechabeng sa lefu la Fabry.”