The long-term safety and efficacy of vestronidase alfa, rhGUS enzyme replacement therapy, in subjects with mucopolysaccharidosis VII
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Molecular Genetics and Metabolism
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Vestronidase 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 noncompliance
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.
Como referenciar
WANG, RAYMOND Y.; FRANCO, JOSE F. da S.; LOPEZ-VALDEZ, JAIME; MARTINS, ESMERALDA; SUTTON, VERNON R.; WHITLEY, CHESTER B.; ZHANG, LIN; CIMMS, TRICIA; MARSDEN, DEBORAH; JURECKA, AGNIESZKA; HARMATZ, PAUL. The long-term safety and efficacy of vestronidase alfa, rhGUS enzyme replacement therapy, in subjects with mucopolysaccharidosis VII. Molecular Genetics and Metabolism, v. 129, n. 3, p. 219-227, 2020. DOI: 10.1016/j.ymgme.2020.01.003. Disponível em: http://repositorio.ipen.br/handle/123456789/31398. Acesso em: 30 Dec 2025.
Esta referência é gerada automaticamente de acordo com as normas do estilo IPEN/SP (ABNT NBR 6023) e recomenda-se uma verificação final e ajustes caso necessário.