Mitsva Yekuedza Mibairo yeGene Therapy yeSevere Hemophilia A

BioMarin Pharmaceutical Inc. nhasi yazivisa kuburitswa kwezvakabuda muChidzidzo cheChikamu chechitatu GENEr3-8 chevaloctocogene roxaparvovec, chirongwa chekuongorora majini chekurapa vanhu vakuru vane hemophilia yakakomba A, muNew England Journal of Medicine (NEJM). Chinyorwa chakanzi, "Valoctocogene Roxaparvovec Gene Therapy for Hemophilia A," inoshuma gore rimwe kana kupfuura zvekutevera data kubva muchidzidzo uye inotaurwa mupepeti yakaburitswa mumagazini imwecheteyo yeJournal ichibvuma kubatsira kungangoita zero kubuda ropa uye kudzivirira. kushandiswa kweprophylactic therapy.  

Chinyorwa chepakutanga chekutsvagisa chinoshuma kuti zvichitevera kuisirwa kumwe chete kwevaloctocogene roxaparvovec vatori vechikamu vakawana zvakanyanya kuderedzwa kwegore rekubuda ropa, kuderedzwa kwechinhu VIII kushandiswa, uye kuwedzera factor VIII chiitiko, kupfuura zvavakaita mugore risati rasvika kudzidza kunyoresa. Munhamba yakagara yakatsanangurwa rollover inosanganisira vatori vechikamu 112 vakanyoreswa kubva kune vangangove vasina kupindira kudzidza, zvinoreva gore negore chinhu VIII kuisa pfungwa pakushandisa uye zvinoreva kurapwa kwekubuda kweropa mushure mevhiki 4 yakaderera mushure mekunyudzwa ne99% uye 84%, zvichiteerana (zvose P <0.001) . Pakazere, vatori vechikamu 121/134 (90%) vanga vasina kubuda ropa rakarapwa kana kushomeka kweropa mushure mekunyudzwa, zvichienzaniswa nefactor VIII prophylaxis sezvakanyorwa mune isingapindire kudzidza. Pamasvondo 49-52, 88% yevatori vechikamu vaiva nemedian factor VIII basa re5 IU/dL kana kupfuura, sekuyerwa vachishandisa chromogenic substrate (CS) assay. 

“Kubuda kweropa kunomirira mutoro mukuru wekutarisira zvirwere uye kudiwa kwekurapa kusingakwane kuvanhu vazhinji. Ndinokurudzirwa kuti mugore rekutanga rekurapa, 90% yevatori vechikamu muzvidzidzo vanga vaine zero yakarapwa kubuda ropa kana kushomeka kweropa mushure mekuisirwa pane nefactor VIII prophylaxis, "akadaro Margareth C. Ozelo, MD, PhD, Director, Hemocentro UNICAMP. Yunivhesiti yeCampinas uye Mutungamiri Mukuru Muongorori weGENEr8-1 Chidzidzo. "Izvi zvabuda zvinoratidza mukana wekuchengetedza kubuda ropa kwehemostatic nejini rekurapa hemophilia A."

"Tinodada kuva mapiyona mukudzidza kwegene therapy kune yakanyanya hemophilia A uye kugovera dhata remurwere mumwe nemumwe rinogonesa kunzwisisa kwakazara kweseti yedata remushonga uyu unogona kushandura," akadaro Hank Fuchs, MD, Mutungamiriri weNyika Yese. Tsvagiridzo uye Kubudirira paBioMarin. “Valoctocogene roxaparvovec yakadzidzwa kwenguva refu kupfuura chero ipi zvayo mushonga wegene yehemophilia A, uye gore negore, tinoramba tichiwedzera ruzivo rwedu rwekuti kurapa kwekuongorora uku kungabatsire sei hupenyu hwevanhu vane hemophilia A. Tinotenda kune vakapinda muchidzidzo. uye vaongorori vebasa ravo rakakosha muchirongwa ichi chebudiriro, chinosanganisira GENEr8-1, chidzidzo chikuru chegene therapy muhemophilia A.

Valoctocogene Roxaparvovec Kuchengetedza

Urwu ndirwo ruzivo rwazvino rwekuchengetedza kubva muongororo yemakore maviri yeChidzidzo cheChitatu GENEr3-8 uye inovhara kuchengetedzwa kwese kwevaloctocogene roxaparvovec. Kuchengetedzwa kunosanganisirwa mukuburitswa kweNEJM kunobva pakuongorora kwegore rimwe chete. Vese vatori vechikamu muChidzidzo cheChikamu 1 vakagamuchira imwechete 3e6 vg/kg dose. Hapana vatori vechikamu vakagadzira inhibitors kuFactor VIII, kuipa, kana thromboembolic zviitiko. Mugore rechipiri, hapana zviratidzo zvitsva zvekuchengetedza zvakabuda, uye hapana zviitiko zvakakomba zvine chekuita nekurapa (SAE) zvakashumwa. Varwere vakawanda vakanga varega chero corticosteroid (CS) kushandiswa mugore rokutanga, uye pakanga pasina maSAE ane chokuita neCS mune varwere vakasara vari kubviswa CS mugore rechipiri. Pakazere, izvo zvinowanzoitika zvakashata zviitiko (AE) zvine chekuita ne valoctocogene roxaparvovec zvakaitika kare uye zvaisanganisira kupindira kwechinguvana kwakabatana maitiro uye kupfava kusvika pakati nepakati kusimuka kwema enzymes echiropa asina anogara kwenguva refu ekiriniki sequelae. Alanine aminotransferase (ALT) kukwidziridzwa (13 vatori vechikamu, 119%), murabhoritari bvunzo yekushanda kwechiropa, yakaramba iri yakajairika AE. Zvimwe zviitiko zvakashata zvinowanzoitika ndezvemusoro (89 vatori vechikamu, 55%), arthralgia (41 vatori vechikamu, 53%), kusvotwa (40 vatori vechikamu, 51%), aspartate aminotransferase (AST) kukwirira (38 vatori vechikamu, 47%), uye kuneta (35). vatori vechikamu, 40%). Muchidzidzo cheChikamu 30/1, SAE ye salivary gland mass yakaonekwa mune mumwe mudzidzi wezvidzidzo, uyo akabatwa makore anopfuura mashanu apfuura, uye akanzi haana hukama ne valoctocogene roxaparvovec nemuongorori. Vakuru vehutano vakakodzera vakaziviswa mukupera kwa2, uye zvidzidzo zvese zvinoramba zvichienderera pasina kugadziridzwa. Dare rakazvimirira reData Monitoring Committee (DMC) rakazoongororazve nyaya iyi. A genomic analysis iri kuitwa sezvinotsanangurwa mukiriniki yekuedza protocol. 

GENER8-1 Tsanangudzo Yekudzidza

Chidzidzo chepasi rose Phase 3 GENEr8-1 chidzidzo cheruoko chimwechete, chakavhurika-label chinoongorora kushanda uye kuchengetedzeka kwevaloctocogene roxaparvovec muvanhu vane hemophilia A (FVIII ≤ 1 IU/dL) vanga vachirapwa nguva dzese neprophylactic exogenous factor VIII. kwerisingasviki gore risati ranyoreswa. Iyo yekutanga efficacy endpoint yaive shanduko kubva padanho rekutanga mu factor VIII basa (CS assay) pamavhiki 49-52 mushure mekunyudzwa. Sekondari efficacy endpoints yaisanganisira kuchinja kubva kune imwe nheyo mukushandiswa kwegore negore kwechikonzero VIII kuisa pfungwa uye gore negore nhamba yezvikamu zvekubuda ropa mushure mevhiki 4. Kuchengetedzwa kwakaongororwa kuburikidza nekurekodha kwezviitiko zvakashata, kuongororwa kwe laboratory, uye kuongorora muviri. Kakawanda, vatori vechikamu 134 vakagamuchira imwe valoctocogene roxaparvovec infusion pamutengo we6e13 vg / kg, uye vose vatori vechikamu vaiva nehuwandu hwemwedzi ye12 yekutevera panguva yekucheka data. Vatori vechikamu makumi maviri nevaviri vekutanga vakanyoreswa zvakananga muChidzidzo cheChikamu 22, gumi nevanomwe vavo vaive vasina hutachiona hweHIV uye vakapihwa kangani makore maviri zuva rekuchekwa kwedata risati rasvika. Vakasara ve3 vatori vechikamu (rollover population) vakapedza mwedzi mitanhatu mune imwe yedzidzo yakasiyana-siyana isiri-yekupindira kuti vatarise zvikamu zvekubuda ropa, kushandiswa kwechinhu VIII, uye hutano hwehutano hwehupenyu apo vachigamuchira factor VIII prophylaxis vasati vatenderera uye kugamuchira imwe chete. infusion ye valoctocogene roxaparvovec muGENEr17-2 kudzidza.