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

Joseph Muenzer, James E. Wraith, Michael Beck, Roberto Giugliani, Paul Harmatz, Christine M. Eng, Ashok Vellodi, Rick Martin, Uma Ramaswami, Muge Gucsavas-Calikoglu, Suresh Vijayaraghavan, Suzanne Wendt, Antonio Puga, Brian Ulbrich, Marwan Shinawi, Maureen Cleary, Diane Piper, Ann Marie Conway, Alan Kimura

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448 Scopus citations

Abstract

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 = 0.0049 for weekly and P = 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 = 0.013), a 2.7% increase in percentage of predicted forced vital capacity (P = 0.065), and a 160 mL increase in absolute forced vital capacity (P = 0.001) compared to placebo group at 53 weeks. Idursulfase was generally well tolerated, but infusion reactions did occur. Idursulfase antibodies were detected in 46.9% of patients during the study. CONCLUSION: This study supports the use of weekly infusions of idursulfase in the treatment of mucopolysaccharidosis II.

Original languageEnglish
Pages (from-to)465-473
Number of pages9
JournalGenetics in Medicine
Volume8
Issue number8
DOIs
StatePublished - Aug 2006

Keywords

  • Enzyme replacement therapy
  • Hunter syndrome
  • Lysosomal storage disease
  • Mucopolysaccharidosis II

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