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

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176 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)469-475
Number of pages7
JournalMolecular Genetics and Metabolism
Volume94
Issue number4
DOIs
StatePublished - Aug 2008

Bibliographical note

Funding Information:
We acknowledge the participation of study patients and their families and the expert assistance of all study site coordinators and study site personnel. We also acknowledge the key contributions of our colleagues Dr. Ann Lowe and Ms. Mary Newman as well as the many other BioMarin employees and consultants who performed important roles during the studies. This study was sponsored by BioMarin Pharmaceutical Inc., and supported, in part, with funds provided by the National Center for Research Resources, 5 M01 RR-01271 (Dr. Harmatz), 5 M01 RR-00400 (Dr. Whitley), M01 RR-00334 (Dr. Steiner), and UL1-RR-024134 (Dr. Kaplan). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Keywords

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

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