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The long-term safety and efficacy of vestronidase alfa, rhGUS enzyme replacement therapy, in subjects with mucopolysaccharidosis VII

2020Journal article Open access
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dc.contributor.authorWang, Raymond Y.
dc.contributor.authorda Silva Franco, José Francisco
dc.contributor.authorLópez-Valdez, Jaime
dc.contributor.authorMartins, Esmeralda
dc.contributor.authorSutton, Vernon Reid
dc.contributor.authorWhitley, Chester B.
dc.contributor.authorZhang, Lin
dc.contributor.authorCimms, Tricia
dc.contributor.authorMarsden, Deborah
dc.contributor.authorJurecka, Agnieszka
dc.contributor.authorHarmatz, Paul
dc.date.accessioned2022-03-31T10:21:39Z
dc.date.available2022-03-31T10:21:39Z
dc.date.issued2020
dc.description.abstractVestronidase alfa (recombinant human beta-glucuronidase) is an enzyme replacement therapy (ERT) for Mucopolysaccharidosis (MPS) VII, a highly heterogeneous, ultra-rare disease. Twelve subjects, ages 8-25 years, completed a Phase 3, randomized, placebo-controlled, blind-start, single crossover study (UX003-CL301; NCT02377921), receiving 24-48 weeks of vestronidase alfa 4 mg/kg IV. All 12 subjects completed the blind-start study, which showed significantly reduced urinary glycosaminoglycans (GAG) and clinical improvement in a multi-domain responder index, and enrolled in a long-term, open-label, extension study (UX003-CL202; NCT02432144). Here, we report the final results of the extension study, up to an additional 144 weeks after completion of the blind-start study. Three subjects (25%) completed all 144 weeks of study, eight subjects (67%) ended study participation before Week 144 to switch to commercially available vestronidase alfa, and one subject discontinued due to non-compliance after receiving one infusion of vestronidase alfa in the extension study. The safety profile of vestronidase alfa in the extension study was consistent with observations in the preceding blind-start study, with most adverse events mild to moderate in severity. There were no treatment or study discontinuations due to AEs and no noteworthy changes in a standard safety chemistry panel. Out of the eleven subjects who tested positive for anti-drug antibodies at any time during the blind-start or extension study, including the baseline assessment in the blind-start study, seven subjects tested positive for neutralizing antibodies and all seven continued to demonstrate a reduction in urinary GAG levels. There was no association between antibody formation and infusion associated reactions. Subjects receiving continuous vestronidase alfa treatment showed a sustained urinary GAG reduction and clinical response evaluated using a multi-domain responder index that includes assessments in pulmonary function, motor function, range of motion, mobility, and visual acuity. Reduction in fatigue was also maintained in the overall population. As ERT is not expected to cross the blood brain barrier, limiting the impact on neurological signs of disease, and not all subjects presented with neurological symptoms, outcomes related to central nervous system pathology are not focused on in this report. Results from this study show the long-term safety and durability of clinical efficacy in subjects with MPS VII with long-term vestronidase alfa treatment.pt_PT
dc.description.sponsorshipThis work was supported by Ultragenyx Pharmaceutical Inc. LZ, TC, DM, and AJ, authors of this manuscript, are employees of Ultragenyx Pharmaceutical and contributed to the conduct of the research; the study design; data collection, analysis and interpretation; development of this manuscript; and the decision to submit this article.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationWang RY, da Silva Franco JF, López-Valdez J, et al. The long-term safety and efficacy of vestronidase alfa, rhGUS enzyme replacement therapy, in subjects with mucopolysaccharidosis VII [published correction appears in Mol Genet Metab. 2020 Sep - Oct;131(1-2):285]. Mol Genet Metab. 2020;129(3):219-227. doi:10.1016/j.ymgme.2020.01.003pt_PT
dc.identifier.doi10.1016/j.ymgme.2020.01.003pt_PT
dc.identifier.issn1096-7192
dc.identifier.issn1096-7206
dc.identifier.urihttp://hdl.handle.net/10400.16/2679
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAcademic Presspt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S1096719219307851?via%3Dihubpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectEnzyme replacement therapypt_PT
dc.subjectGlycosaminoglycanspt_PT
dc.subjectMPS VIIpt_PT
dc.subjectMucopolysaccharidosispt_PT
dc.subjectSly syndromept_PT
dc.subjectTreatmentpt_PT
dc.titleThe long-term safety and efficacy of vestronidase alfa, rhGUS enzyme replacement therapy, in subjects with mucopolysaccharidosis VIIpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceUnited States of Americapt_PT
oaire.citation.endPage227pt_PT
oaire.citation.issue3pt_PT
oaire.citation.startPage219pt_PT
oaire.citation.titleMolecular Genetics and Metabolismpt_PT
oaire.citation.volume129pt_PT
person.familyNameMartins
person.givenNameEsmeralda
person.identifier.ciencia-idBF1C-DAE5-FAEA
person.identifier.orcid0000-0002-9247-9391
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication7f4a528c-bf0f-4895-ac98-4353fe38c68a
relation.isAuthorOfPublication.latestForDiscovery7f4a528c-bf0f-4895-ac98-4353fe38c68a

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