Enzyme replacement therapy for mucopolysaccharidosis VI: A phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study

Harmatz, Paul; Giugliani, Roberto; Schwartz, Ida Vanessa Döederlein; Guffon, Nathalie; Teles, Elisa Leão; Sá-Miranda, Clara; Wraith, J. Edmond; Beck, Michael; Arash, Laila; Scarpa, Maurizio; Yu, Zi‐Fan; Wittes, Janet; Berger, Kenneth I.; Newman, Mary S.; Lowe, Ann M.; Kakkis, Emil; Swiedler, Stuart J.

doi:10.1016/j.jpeds.2005.12.014

Cited by 341 publications

(270 citation statements)

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“…Enzyme replacement therapy has been previously developed for MPS I 20,22 and MPS VI, 24,25 as well as for other lysosomal storage diseases. 26 -28 Both MPS I and MPS VI are caused by deficiencies in single enzymes involved in the catabolism of GAG, 1 and like MPS II, their phenotypic expression varies considerably.…”

Section: Discussionmentioning

confidence: 99%

“…24,25 In the MPS I double-blind, placebo-controlled phase III ERT study reported by Wraith and coworkers, 6 months of treatment with laronidase (recombinant ␣-L-iduronidase) significantly decreased urinary GAG, decreased liver and spleen volumes, improved %FVC (based on each patient's current height) by 4.3% (P ϭ 0.022) and increase the 6MWT distance by 38 m (P ϭ 0.066) compared to placebo. 22 In the MPS VI double-blind phase, placebo-controlled phase III ERT study, 6 months of treatment with galsulfase (recombinant human N-acetylgalactosamine 4-sulfatase) decreased urinary GAG and the distance walked in 12 minutes showed a longitudinal model-derived mean difference of 92 Ϯ 40 m (P ϭ 0.025) in favor of galsulfase.…”

Section: Discussionmentioning

confidence: 99%

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A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome)

Muenzer

Wraith

Beck³

et al. 2006

Genetics in Medicine

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Purpose: To evaluate the safety and efficacy of recombinant human iduronate-2-sulfatase (idursulfase) in the treatment of mucopolysaccharidosis II. Methods: Ninety-six mucopolysaccharidosis II patients between 5 and 31 years of age were enrolled in a double-blind, placebo-controlled trial. Patients were randomized to placebo infusions, weekly idursulfase (0.5 mg/kg) infusions or every-other-week infusions of idursulfase (0.5 mg/kg).Efficacy was evaluated using a composite endpoint consisting of distance walked in 6 minutes and the percentage of predicted forced vital capacity based on the sum of the ranks of change from baseline. Results: Patients in the weekly and every-other-week idursulfase groups exhibited significant improvement in the composite endpoint compared to placebo (P ϭ 0.0049 for weekly and P ϭ 0.0416 for every-other-week) after one year. The weekly dosing group experienced a 37-m increase in the 6-minute-walk distance (P ϭ 0.013), a 2.7% increase in percentage of predicted forced vital capacity (P ϭ 0.065), and a 160 mL increase in absolute forced vital capacity (P ϭ 0.001) compared to placebo group at 53 weeks. Idursulfase was generally well tolerated, but infusion reactions did occur.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome)

Muenzer

Wraith

Beck³

et al. 2006

Genetics in Medicine

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512

509

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“…In the past, several studies have used endurance tests such as the 6MWT, and more recently the 3MSCT, to assess the impact of ERT on overall disease progression in MPS disorders [Harmatz et al, 2006; Hendriksz et al, [Link]; Muenzer et al, 2006; Wraith et al, 2004]. However, the physiological correlates of these tests are not well characterized.…”

Section: Discussionmentioning

confidence: 99%

Safety and physiological effects of two different doses of elosulfase alfa in patients with morquio a syndrome: A randomized, double‐blind, pilot study

Burton

Berger

Lewis

et al. 2015

American J of Med Genetics Pt A

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The primary treatment outcomes of a phase 2, randomized, double‐blind, pilot study evaluating safety, physiological, and pharmacological effects of elosulfase alfa in patients with Morquio A syndrome are herewith presented. Patients aged ≥7 years and able to walk ≥200 m in the 6‐min walk test (6MWT) were randomized to elosulfase alfa 2.0 or 4.0 mg/kg/week for 27 weeks. The primary objective was to evaluate the safety of both doses. Secondary objectives were to evaluate effects on endurance (6MWT and 3‐min stair climb test [3MSCT]), exercise capacity (cardio‐pulmonary exercise test [CPET]), respiratory function, muscle strength, cardiac function, pain, and urine keratan sulfate (uKS) levels, and to determine pharmacokinetic parameters. Twenty‐five patients were enrolled (15 randomized to 2.0 mg/kg/week and 10 to 4.0 mg/kg/week). No new or unexpected safety signals were observed. After 24 weeks, there were no improvements versus baseline in the 6MWT, yet numerical improvements were seen in the 3MSCT with 4.0 mg/kg/week. uKS and pharmacokinetic data suggested no linear relationship over the 2.0–4.0 mg/kg dose range. Overall, an abnormal exercise capacity (evaluated in 10 and 5 patients in the 2.0 and 4.0 mg/kg/week groups, respectively), impaired muscle strength, and considerable pain were observed at baseline, and there were trends towards improvements in all domains after treatment. In conclusion, preliminary data of this small study in a Morquio A population with relatively good endurance confirmed the acceptable safety profile of elosulfase alfa and showed a trend of increased exercise capacity and muscle strength and decreased pain. © 2015 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

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“…We pooled cross-sectional and longitudinal height for age data from patients who participated in the MPS VI crosssectional Survey Study done in 2001-2002(Swiedler et al 2005; clinical trials and their extension programs, including phase 1/2, phase 2, phase 3 (Harmatz et al 2004;Harmatz et al 2005;Harmatz et al 2006;Harmatz et al 2008), and a phase 4 study ; the MPS VI clinical surveillance program (CSP; ClinicalTrials.gov: NCT00214773); and the Resurvey Study (Giugliani et al 2014) to construct growth charts for patients with the MPS VI disorder. Patients treated with galsulfase (recombinant human arylsulfatase B; rhASB; Naglazyme ® ; an enzyme replacement therapy [ERT] for MPS VI) or patients status post hematopoietic stem cell transplant (HSCT) were excluded from this analysis.…”

Section: Data Source For Integrated Height Analysismentioning

confidence: 99%

Growth Charts for Individuals with Mucopolysaccharidosis VI (Maroteaux–Lamy Syndrome)

et al. 2014

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Background: The skeletal phenotype of mucopolysaccharidosis VI (MPS VI) is characterized by short stature and growth failure.Objective: The purpose of this study was to construct reference growth curves for MPS VI patients with rapidly and slowly progressive disease.Methods: We pooled cross-sectional and longitudinal height for age data from galsulfase (Naglazyme ® , BioMarin Pharmaceutical Inc.), treatment naïve patients (n ¼ 269) who participated in various MPS VI studies, including galsulfase clinical trials and their extension programs, the MPS VI clinical surveillance program (CSP), and the MPS VI survey and resurvey studies, to construct growth charts for the MPS VI population. There were 229 patients included in this study, of which data from 207 patients 25 years of age with 513 height measurements were used for constructing reference growth curves.Results: Height for age growth curves for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles were constructed for patients with rapidly and slowly progressing disease defined by the pre-enzyme replacement therapy (ERT) uGAG levels of > or 200 mg/mg creatinine. The mean (SD) pre-ERT uGAG levels were 481.0 (218.6) and 97.8 (56.3) mg/mg creatinine for the patients 25 years of age with rapidly (n ¼ 131) and slowly (n ¼ 76) progressing MPS VI disease, respectively. The median growth curves for patients with and >200 mg/mg creatinine were above and below the median (50th percentile) growth curve for the entire MPS VI population.Conclusion: MPS VI growth charts have been developed to assist in the clinical management of MPS VI patients.

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Enzyme replacement therapy for mucopolysaccharidosis VI: A phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study

Cited by 341 publications

References 19 publications

A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome)

A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome)

Safety and physiological effects of two different doses of elosulfase alfa in patients with morquio a syndrome: A randomized, double‐blind, pilot study

Growth Charts for Individuals with Mucopolysaccharidosis VI (Maroteaux–Lamy Syndrome)

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