Nsonaazụ Ọnwụnwa ọhụrụ nke ọgwụgwọ mkpụrụ ndụ ihe nketa maka Hemophilia siri ike A

BioMarin Pharmaceutical Inc. taa kwupụtara mbipụta nke nsonaazụ sitere na usoro 3 GENEr8-1 ọmụmụ nke valoctocogene roxaparvovec, usoro ọgwụgwọ mkpụrụ ndụ nyocha maka ọgwụgwọ ndị okenye nwere nnukwu hemophilia A, na New England Journal of Medicine (NEJM). Isiokwu a kpọrọ, "Valoctocogene Roxaparvovec Gene Therapy for Hemophilia A," na-akọ otu afọ ma ọ bụ karịa nke data nleba anya site na ọmụmụ ihe ahụ ma depụta ya na nchịkọta akụkọ nke e bipụtara n'otu mbipụta nke Journal ahụ na-ekwenye na uru nwere ike ịnweta ọbara efu na izere. ojiji nke prophylactic ọgwụgwọ.  

Edemede nyocha mbụ na-akọ na n'eso otu ntinye nke valoctocogene roxaparvovec ndị sonyere nwere mbelata nke ukwuu ọnụego ọbara ọgbụgba kwa afọ, mbelata ojiji nke VIII, yana mmụba nke ihe VIII, karịa ka ha mere n'afọ tupu ndebanye aha ọmụmụ. N'ime ọnụ ọgụgụ rollover akọwapụtagoro nke ọma nwere ndị sonyere 112 debanyere aha site na ọmụmụ ihe na-aga n'ihu na-abụghị nke etiti, pụtara ihe na-eme kwa afọ nke VIII itinye uche n'ọrụ yana pụtara ọgwụgwọ ọbara ọgbụgba mgbe izu 4 gachara belata ntinye ntinye site na 99% na 84%, n'otu n'otu (ma P<0.001) . N'ozuzu, 121/134 (90%) ndị sonyere enweghị ọbara a na-agwọ ma ọ bụ ọbara ọbara ole na ole a na-agwọ mgbe ha na-agbanye ya, ma e jiri ya tụnyere ihe VIII prophylaxis dị ka e depụtara na ọmụmụ ihe na-abụghị nke etiti. N'ime izu 49-52, 88% nke ndị sonyere nwere ọrụ etiti ihe VIII nke 5 IU / dL ma ọ bụ karịa, dị ka atụpụtara site na iji chromogenic substrate (CS). 

“Ọbara ọgbụgba na-egosi oke ibu nke nlekọta ọrịa yana mkpa ahụike na-egbobeghị maka ọtụtụ mmadụ. A na-agba m ume na n'ime afọ mbụ nke ọgwụgwọ, 90% nke ndị na-amụ ihe nwere ma ọ bụ zero na-agwọ ọbara ọbara ma ọ bụ obere ọbara na-agwọ ọrịa na-esote infusion karịa ihe kpatara VIII prophylaxis, "ka Margareth C. Ozelo, MD, PhD, Director, Hemocentro UNICAMP kwuru. Mahadum nke Campinas na onye ndu isi nyocha nke ọmụmụ GENER8-1. "Nsonaazụ ndị a na-egosipụta ikike nke ịchịkwa ọbara ọgbụgba na-adịgide adịgide site na usoro ọgwụgwọ mkpụrụ ndụ ihe nketa maka hemophilia A."

Hank Fuchs, MD, Onye isi oche nke Worldwide kwuru, "Anyị nwere mpako na anyị bụ ndị ọsụ ụzọ n'ịmụ usoro ọgwụgwọ mkpụrụ ndụ maka hemophilia siri ike na ịkekọrịta data onye ọrịa n'otu n'otu nke na-eme ka nghọta zuru oke nke usoro data nke ọgwụ a nwere ike ịgbanwe. Nnyocha na mmepe na BioMarin. “A mụọla Valoctocogene roxaparvovec ogologo oge karịa usoro ọgwụgwọ mkpụrụ ndụ ọ bụla ọzọ maka hemophilia A, na kwa afọ, anyị na-aga n'ihu na-amụbawanye ihe ọmụma anyị banyere otú ọgwụgwọ nyocha a nwere ike isi rite uru na ndụ ndị nwere hemophilia A. Anyị nwere ekele maka ndị sonyere ọmụmụ ihe. na ndị nyocha maka ọrụ dị mkpa ha na mmemme mmepe a, nke gụnyere GENEr8-1, ọmụmụ ọgwụgwọ mkpụrụ ndụ ihe nketa kacha ukwuu na hemophilia A.”

Nchekwa Valoctocogene Roxaparvovec

Nke a bụ ozi nchekwa kachasị ugbu a site na nyocha afọ abụọ nke usoro ọmụmụ 3 GENEr8-1 ma kpuchie nchekwa zuru oke nke valoctocogene roxaparvovec. Nchekwa gụnyere na mbipụta NEJM dabere na nyocha otu afọ. Ndị niile sonyere na ọmụmụ ihe nke 3 nwetara otu dose 6e13 vg/kg. Ọ nweghị ndị sonyere na-emepụta ihe mgbochi na Factor VIII, malignancy, ma ọ bụ ihe omume thromboembolic. N'ime afọ abụọ, ọnweghị akara nchekwa ọhụrụ pụtara, ọ nweghịkwa ihe omume ọjọọ metụtara ọgwụgwọ (SAE). Ọtụtụ ndị ọrịa akwụsịla ihe ọ bụla corticosteroid (CS) na-eji n'ime otu afọ, ọ dịghịkwa CS metụtara CS na ndị ọrịa fọdụrụnụ na-ewepụ CS n'afọ abụọ. N'ozuzu, ihe ọjọọ na-emekarị (AE) jikọtara na valoctocogene roxaparvovec mere n'isi ma gụnye mmeghachi omume na-adịru nwa oge na mmeghachi omume dị nro na ịrị elu nke enzymes imeju na-enweghị usoro ọgwụgwọ na-adịte aka. Alanine aminotransferase (ALT) elu (ndị sonyere 119, 89%), nyocha ụlọ nyocha nke ọrụ imeju, nọgidere na-abụkarị AE. Ihe omume ọjọọ ndị ọzọ na-emekarị bụ isi ọwụwa (ndị sonyere 55, 41%), ogbu na nkwonkwo (ndị sonyere 53, 40%), ọgbụgbọ (ndị sonyere 51, 38%), elu aspartate aminotransferase (AST) (ndị sonyere 47, 35%), na ike ọgwụgwụ (40). ndị sonyere, 30%). N'ime usoro 1/2 nke ọmụmụ, a chọpụtara SAE nke ụbụrụ salivary gland n'otu onye na-amụ ihe, bụ onye a na-emeso ihe karịrị afọ ise gara aga, ma kọọrọ ya dị ka ihe na-enweghị njikọ na valoctocogene roxaparvovec site na onye nyocha. A mara ọkwa ndị ọrụ ahụike dị mkpa na ngwụcha 2021, ọmụmụ ihe niile na-aga n'ihu na-enweghị mgbanwe. Kọmiti na-ahụ maka data nọọrọ onwe ya (DMC) tụleghachikwara ikpe ahụ. A na-eme nyocha nke genomic dị ka akọwapụtara na ụkpụrụ nnwale ụlọ ọgwụ. 

GENER8-1 Nkọwa Ọmụmụ

Ọmụmụ ihe ọmụmụ 3 GENER8-1 zuru ụwa ọnụ bụ otu ogwe aka, nke na-emeghe akara ngosi nke na-enyocha ịdị irè na nchekwa nke valoctocogene roxaparvovec na ndị nwere nnukwu hemophilia A (FVIII ≤ 1 IU / dL) bụ ndị a na-emeso ya mgbe niile na prophylactic exogenous factor VIII. maka opekempe nke otu afọ tupu ndebanye aha. Isi njedebe nrụpụta ọrụ bụ mgbanwe site na ntọala n'ihe ọrụ VIII (CS assay) na izu 49-52 mgbe infusion gasịrị. Ngwugwu arụmọrụ nke abụọ gụnyere mgbanwe site na ntọala n'iji kwa afọ nke ihe VIII na-etinye uche na ọnụ ọgụgụ ọbara ọgbụgba kwa afọ mgbe izu 4 gasịrị. A na-enyocha nchekwa site na ndekọ nke ihe ọjọọ, nyocha ụlọ nyocha, na nyocha anụ ahụ. N'ozuzu, ngụkọta nke ndị sonyere 134 natara otu valoctocogene roxaparvovec infusion na dose nke 6e13 vg / kg, na ndị niile sonyere nwere opekempe nke ọnwa 12 na-esochi n'oge mbelata data. Ndị sonyere 22 mbụ debanyere aha ozugbo na ọmụmụ ihe nke 3, 17 n'ime ha bụ nje HIV na dosed ma ọ dịkarịa ala afọ 2 tupu ụbọchị ebipụ data. Ndị so na 112 fọdụrụnụ (ọnụọgụ rollover) gụchara ma ọ dịkarịa ala ọnwa isii n'ime ọmụmụ ihe dị iche iche na-abụghị nke na-emekọrịta ihe iji nyochaa ọnọdụ ọbara ọgbụgba, ihe kpatara VIII, na ndụ ndụ metụtara ahụike mgbe ha na-anata prophylaxis ihe nke VIII tupu ịkwaga na ịnweta otu. ntinye nke valoctocogene roxaparvovec na ọmụmụ GENER8-1.