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

Wang, Raymond; Franco, José Francisco da Silva; López-Valdez, Jaime; Martins, Esmeralda; Sutton, V. Reid; Whitley, Chester B.; Zhang, Lin; Cimms, Tricia; Marsden, Deborah; Jurecka, Agnieszka; Harmatz, Paul

doi:10.1016/j.ymgme.2020.01.003

Cited by 24 publications

(16 citation statements)

References 33 publications

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“…Vestronidase alfa is a formulation of recombinant human β-glucuronidase (rhGUS; UX003 -Ultragenyx Pharmaceutical Inc.), approved by the Food and Drug Administration (FDA) in 2017 and in 2018 by Agência Nacional de Vigilância Sanitária (ANVISA-Brazil) to treat children and adults with MPS VII. These approvals were based on ndings from studies including noninterventional reviews of medical records, patient surveys, and clinical trials [9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Mucopolysaccharidosis VII in Brazil: Natural History and Clinical Findings

Giugliani

Barth

Dumas³

et al. 2021

Preprint

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Background: Mucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome, caused by deficiency of the lysosomal enzyme β-glucuronidase, is an ultra-rare disorder with scarce epidemiological data and few publications about natural history and clinical spectrum. Methods: We conducted a case series report which included retrospective data from all MPS VII patients diagnosed through the “MPS Brazil Network” who were known to be alive in 2020 in Brazil (N=13). Clinical data were obtained from a review of the medical records and descriptive statistics and variables were summarized using counts and percentages of the total population.Results: The majority of the patients were from the Northeast region of Brazil. Among the signs and symptoms that raised the clinical suspicion of MPS, coarse face was the most frequent; 58% of the patients had a history of non-immune hydrops fetalis. All the subjects presented short neck and trunk. The majority presented typical phenotypical signs of MPS disorders. They all presented neurodevelopmental delay and cognitive impairment. About half of this cohort had knees deformities. Dysostosis multiplex was identified in almost all patients and cardiomyopathy was less frequent than observed in other types of MPSs. The mean age at diagnosis was 5 years, ranging from 1 to 14 years. Almost all patients (12/13) were homozygous for the c.526C>T (p.Leu176Phe) mutation. A novel variant of the GUSB gene was found, the c.875T>C (p.Leu292Pro), in a compound heterozygous with the c.526C>T (p.Leu176Phe) variant.Conclusions: This case series is the biggest data collection of MPS VII patients alive in Latin America. The overall clinical picture of the MPS VII patients is very similar to other MPS disorders, including broad spectrum of severity and delayed diagnosis.

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Section: Introductionmentioning

confidence: 99%

Mucopolysaccharidosis VII in Brazil: Natural History and Clinical Findings

Giugliani

Barth

Dumas³

et al. 2021

Preprint

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“…Mean reductions in DS and CS in the continuation period were 54.8% and 46.7%, respectively. Although interpretation of the safety and efficacy data in this study are limited by the heterogeneity, small sample size (n = 3), and change over time in clinical symptoms, these results were confirmed in a phase 3 study in which treatment with vestronidase alfa at 24 weeks led to significant decreases in uGAG excretion that were maintained for up to an additional 144 weeks [ 9 , 10 ].…”

Section: Discussionmentioning

confidence: 57%

“…In a randomized, placebo-controlled, phase 3 study (N = 12), vestronidase alfa 4 mg/kg administered intravenously every other week (QOW) for 24 weeks significantly reduced urinary GAG (uGAG) excretion, and most subjects with MPS VII exhibited improvement in other clinical and patient-reported outcomes [ 8 , 9 ]. In the open-label, long-term extension, reductions in uGAG excretion were sustained, and treatment was well tolerated [ 10 ]. In the open-label, phase 1/2 first-in-human study, vestronidase alfa 1–4 mg/kg for the initial 38 weeks of treatment led to reduction in uGAG excretion in subjects with MPS VII [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Open-label phase 1/2 study of vestronidase alfa for mucopolysaccharidosis VII

Jones

Çöker

López

et al. 2021

Molecular Genetics and Metabolism Reports

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Vestronidase alfa is an enzyme replacement therapy for mucopolysaccharidosis VII (MPS VII). In this open-label, phase 1/2 study, three subjects with MPS VII received intravenous vestronidase alfa administered every other week (QOW) for 14 weeks (2 mg/kg), followed by 24-week forced-dose titration (1, 4, and 2 mg/kg QOW; 8 weeks each), 36-week continuation (2 mg/kg), and long-term extension (4 mg/kg). Vestronidase alfa was well tolerated and led to dose-responsive, sustained reductions in urinary glycosaminoglycan excretion.

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“…12 Laboratory of Inborn Errors of Metabolism, Institute of Biological Sciences, Federal University of Pará, INAGEMP, Belém, PA, Brazil. 13 Hospital de Clínicas, Federal University of Uberlândia, Uberlândia, MG, Brazil. 14 Hospital Universitário Bettina Ferro de Souza, Federal University of Pará, Belém, PA, Brazil.…”

Section: Fundingmentioning

confidence: 99%

“…Vestronidase alfa is a formulation of recombinant human β-glucuronidase (rhGUS; UX003-Ultragenyx Pharmaceutical Inc.), approved by the Food and Drug Administration (FDA) in 2017 and in 2018 by Agência Nacional de Vigilância Sanitária (ANVISA-Brazil) to treat children and adults with MPS VII. These approvals were based on findings from studies including non-interventional reviews of medical records, patient surveys, and clinical trials [9][10][11][12][13].…”

mentioning

confidence: 99%

Mucopolysaccharidosis VII in Brazil: natural history and clinical findings

Giugliani

Barth

Dumas³

et al. 2021

Orphanet J Rare Dis

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Background Mucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome, caused by deficiency of the lysosomal enzyme β-glucuronidase, is an ultra-rare disorder with scarce epidemiological data and few publications about natural history and clinical spectrum. Methods We conducted a case series report which included retrospective data from all MPS VII patients diagnosed through the “MPS Brazil Network” who were known to be alive in 2020 in Brazil (N = 13). Clinical data were obtained from a review of the medical records and descriptive statistics and variables were summarized using counts and percentages of the total population. Results The majority of the patients were from the Northeast region of Brazil. Among the signs and symptoms that raised the clinical suspicion of MPS, coarse face was the most frequent; 58% of the patients had a history of non-immune hydrops fetalis. All the subjects presented short neck and trunk. The majority presented typical phenotypical signs of MPS disorders. They all presented neurodevelopmental delay and cognitive impairment. About half of this cohort had knees deformities. Dysostosis multiplex was identified in almost all patients and cardiomyopathy was less frequent than observed in other types of MPSs. The mean age at diagnosis was 5 years, ranging from 1 to 14 years. Almost all patients (12/13) were homozygous for the c.526C>T (p.Leu176Phe) mutation. A novel variant of the GUSB gene was found, the c.875T>C (p.Leu292Pro), in a compound heterozygous with the c.526C>T (p.Leu176Phe) variant. Conclusions This case series is the biggest data collection of MPS VII patients alive in Latin America. The overall clinical picture of the MPS VII patients is very similar to other MPS disorders, including a spectrum of severity and delayed diagnosis.

show abstract

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

Cited by 24 publications

References 33 publications

Mucopolysaccharidosis VII in Brazil: Natural History and Clinical Findings

Mucopolysaccharidosis VII in Brazil: Natural History and Clinical Findings

Open-label phase 1/2 study of vestronidase alfa for mucopolysaccharidosis VII

Mucopolysaccharidosis VII in Brazil: natural history and clinical findings

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