Long-term follow-up of endurance and safety outcomes during enzyme replacement therapy for mucopolysaccharidosis VI: Final results of three clinical studies of recombinant human N-acetylgalactosamine 4-sulfatase

Paul Harmatz, Roberto Giugliani, Ida Vanessa Ida, Nathalie Guffon, Elisa Leão Teles, M. Clara Sá Miranda, J. Edmond Wraith, Michael Beck, Laila Arash, Maurizio Scarpa, David Ketteridge, John J. Hopwood, Barbara Plecko, Robert Steiner, Chester B. Whitley, Paige Kaplan, Zi Fan Yu, Stuart J. Swiedler, Celeste Decker

Research output: Contribution to journalArticle

166 Citations (Scopus)

Abstract

The objective of this study was to evaluate the long-term clinical benefits and safety of recombinant human arylsulfatase B (rhASB) treatment of mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome), a lysosomal storage disease. Fifty-six patients derived from 3 clinical studies were followed in open-label extension studies for a total period of 97-260 Weeks. All patients received weekly infusions of rhASB at 1 mg/kg. Efficacy was evaluated by (1) distance walked in a 12-minute walk test (12MWT) or 6-minute walk test (6MWT), (2) stairs climbed in the 3-minute stair climb (3MSC), and (3) reduction in urinary glycosaminoglycans (GAG). Safety was evaluated by compliance, adverse event (AE) reporting and adherence to treatment. Results: A significant reduction in urinary GAG (71-79%) was sustained. For the 12MWT, subjects in Phase 2 showed improvement of 255 ± 191 m (mean ± SD) at Week 144; those in Phase 3 Extension demonstrated improvement from study baseline of 183 ± 26 m (mean ± SE) in the rhASB/rhASB group at Week 96 and from treatment baseline (Week 24) of 117 ± 25 m in the placebo/rhASB group. The Phase 1/2 6MWT and the 3MSC from Phase 2 and 3 also showed sustained improvements through the final study measurements. Compliance was 98% overall. Only 560 of 4121 reported AEs (14%) were related to treatment with only 10 of 560 (2%) described as severe. Conclusion: rhASB treatment up to 5 years results in sustained improvements in endurance and has an acceptable safety profile.

LanguageEnglish
Pages469-475
Number of pages7
JournalMolecular Genetics and Metabolism
Volume94
Issue number4
DOIs
Publication statusPublished - 1 Aug 2008

Keywords

  • Clinical trial
  • Enzyme replacement therapy
  • Glycosaminoglycans
  • Mucopolysaccharidosis VI
  • N-Acetylgalactosamine-4-sulfatase

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Cite this

Harmatz, Paul ; Giugliani, Roberto ; Ida, Ida Vanessa ; Guffon, Nathalie ; Teles, Elisa Leão ; Miranda, M. Clara Sá ; Wraith, J. Edmond ; Beck, Michael ; Arash, Laila ; Scarpa, Maurizio ; Ketteridge, David ; Hopwood, John J. ; Plecko, Barbara ; Steiner, Robert ; Whitley, Chester B. ; Kaplan, Paige ; Yu, Zi Fan ; Swiedler, Stuart J. ; Decker, Celeste. / Long-term follow-up of endurance and safety outcomes during enzyme replacement therapy for mucopolysaccharidosis VI : Final results of three clinical studies of recombinant human N-acetylgalactosamine 4-sulfatase. In: Molecular Genetics and Metabolism. 2008 ; Vol. 94, No. 4. pp. 469-475.
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title = "Long-term follow-up of endurance and safety outcomes during enzyme replacement therapy for mucopolysaccharidosis VI: Final results of three clinical studies of recombinant human N-acetylgalactosamine 4-sulfatase",
abstract = "The objective of this study was to evaluate the long-term clinical benefits and safety of recombinant human arylsulfatase B (rhASB) treatment of mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome), a lysosomal storage disease. Fifty-six patients derived from 3 clinical studies were followed in open-label extension studies for a total period of 97-260 Weeks. All patients received weekly infusions of rhASB at 1 mg/kg. Efficacy was evaluated by (1) distance walked in a 12-minute walk test (12MWT) or 6-minute walk test (6MWT), (2) stairs climbed in the 3-minute stair climb (3MSC), and (3) reduction in urinary glycosaminoglycans (GAG). Safety was evaluated by compliance, adverse event (AE) reporting and adherence to treatment. Results: A significant reduction in urinary GAG (71-79{\%}) was sustained. For the 12MWT, subjects in Phase 2 showed improvement of 255 ± 191 m (mean ± SD) at Week 144; those in Phase 3 Extension demonstrated improvement from study baseline of 183 ± 26 m (mean ± SE) in the rhASB/rhASB group at Week 96 and from treatment baseline (Week 24) of 117 ± 25 m in the placebo/rhASB group. The Phase 1/2 6MWT and the 3MSC from Phase 2 and 3 also showed sustained improvements through the final study measurements. Compliance was 98{\%} overall. Only 560 of 4121 reported AEs (14{\%}) were related to treatment with only 10 of 560 (2{\%}) described as severe. Conclusion: rhASB treatment up to 5 years results in sustained improvements in endurance and has an acceptable safety profile.",
keywords = "Clinical trial, Enzyme replacement therapy, Glycosaminoglycans, Mucopolysaccharidosis VI, N-Acetylgalactosamine-4-sulfatase",
author = "Paul Harmatz and Roberto Giugliani and Ida, {Ida Vanessa} and Nathalie Guffon and Teles, {Elisa Le{\~a}o} and Miranda, {M. Clara S{\'a}} and Wraith, {J. Edmond} and Michael Beck and Laila Arash and Maurizio Scarpa and David Ketteridge and Hopwood, {John J.} and Barbara Plecko and Robert Steiner and Whitley, {Chester B.} and Paige Kaplan and Yu, {Zi Fan} and Swiedler, {Stuart J.} and Celeste Decker",
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Harmatz, P, Giugliani, R, Ida, IV, Guffon, N, Teles, EL, Miranda, MCS, Wraith, JE, Beck, M, Arash, L, Scarpa, M, Ketteridge, D, Hopwood, JJ, Plecko, B, Steiner, R, Whitley, CB, Kaplan, P, Yu, ZF, Swiedler, SJ & Decker, C 2008, 'Long-term follow-up of endurance and safety outcomes during enzyme replacement therapy for mucopolysaccharidosis VI: Final results of three clinical studies of recombinant human N-acetylgalactosamine 4-sulfatase', Molecular Genetics and Metabolism, vol. 94, no. 4, pp. 469-475. https://doi.org/10.1016/j.ymgme.2008.04.001

Long-term follow-up of endurance and safety outcomes during enzyme replacement therapy for mucopolysaccharidosis VI : Final results of three clinical studies of recombinant human N-acetylgalactosamine 4-sulfatase. / Harmatz, Paul; Giugliani, Roberto; Ida, Ida Vanessa; Guffon, Nathalie; Teles, Elisa Leão; Miranda, M. Clara Sá; Wraith, J. Edmond; Beck, Michael; Arash, Laila; Scarpa, Maurizio; Ketteridge, David; Hopwood, John J.; Plecko, Barbara; Steiner, Robert; Whitley, Chester B.; Kaplan, Paige; Yu, Zi Fan; Swiedler, Stuart J.; Decker, Celeste.

In: Molecular Genetics and Metabolism, Vol. 94, No. 4, 01.08.2008, p. 469-475.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Long-term follow-up of endurance and safety outcomes during enzyme replacement therapy for mucopolysaccharidosis VI

T2 - Molecular Genetics and Metabolism

AU - Harmatz, Paul

AU - Giugliani, Roberto

AU - Ida, Ida Vanessa

AU - Guffon, Nathalie

AU - Teles, Elisa Leão

AU - Miranda, M. Clara Sá

AU - Wraith, J. Edmond

AU - Beck, Michael

AU - Arash, Laila

AU - Scarpa, Maurizio

AU - Ketteridge, David

AU - Hopwood, John J.

AU - Plecko, Barbara

AU - Steiner, Robert

AU - Whitley, Chester B.

AU - Kaplan, Paige

AU - Yu, Zi Fan

AU - Swiedler, Stuart J.

AU - Decker, Celeste

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Y1 - 2008/8/1

N2 - The objective of this study was to evaluate the long-term clinical benefits and safety of recombinant human arylsulfatase B (rhASB) treatment of mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome), a lysosomal storage disease. Fifty-six patients derived from 3 clinical studies were followed in open-label extension studies for a total period of 97-260 Weeks. All patients received weekly infusions of rhASB at 1 mg/kg. Efficacy was evaluated by (1) distance walked in a 12-minute walk test (12MWT) or 6-minute walk test (6MWT), (2) stairs climbed in the 3-minute stair climb (3MSC), and (3) reduction in urinary glycosaminoglycans (GAG). Safety was evaluated by compliance, adverse event (AE) reporting and adherence to treatment. Results: A significant reduction in urinary GAG (71-79%) was sustained. For the 12MWT, subjects in Phase 2 showed improvement of 255 ± 191 m (mean ± SD) at Week 144; those in Phase 3 Extension demonstrated improvement from study baseline of 183 ± 26 m (mean ± SE) in the rhASB/rhASB group at Week 96 and from treatment baseline (Week 24) of 117 ± 25 m in the placebo/rhASB group. The Phase 1/2 6MWT and the 3MSC from Phase 2 and 3 also showed sustained improvements through the final study measurements. Compliance was 98% overall. Only 560 of 4121 reported AEs (14%) were related to treatment with only 10 of 560 (2%) described as severe. Conclusion: rhASB treatment up to 5 years results in sustained improvements in endurance and has an acceptable safety profile.

AB - The objective of this study was to evaluate the long-term clinical benefits and safety of recombinant human arylsulfatase B (rhASB) treatment of mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome), a lysosomal storage disease. Fifty-six patients derived from 3 clinical studies were followed in open-label extension studies for a total period of 97-260 Weeks. All patients received weekly infusions of rhASB at 1 mg/kg. Efficacy was evaluated by (1) distance walked in a 12-minute walk test (12MWT) or 6-minute walk test (6MWT), (2) stairs climbed in the 3-minute stair climb (3MSC), and (3) reduction in urinary glycosaminoglycans (GAG). Safety was evaluated by compliance, adverse event (AE) reporting and adherence to treatment. Results: A significant reduction in urinary GAG (71-79%) was sustained. For the 12MWT, subjects in Phase 2 showed improvement of 255 ± 191 m (mean ± SD) at Week 144; those in Phase 3 Extension demonstrated improvement from study baseline of 183 ± 26 m (mean ± SE) in the rhASB/rhASB group at Week 96 and from treatment baseline (Week 24) of 117 ± 25 m in the placebo/rhASB group. The Phase 1/2 6MWT and the 3MSC from Phase 2 and 3 also showed sustained improvements through the final study measurements. Compliance was 98% overall. Only 560 of 4121 reported AEs (14%) were related to treatment with only 10 of 560 (2%) described as severe. Conclusion: rhASB treatment up to 5 years results in sustained improvements in endurance and has an acceptable safety profile.

KW - Clinical trial

KW - Enzyme replacement therapy

KW - Glycosaminoglycans

KW - Mucopolysaccharidosis VI

KW - N-Acetylgalactosamine-4-sulfatase

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