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, P.Giugliani, R.Schwartz, I.Guffon, N.Teles, E.Miranda, C.Wraith, J.Beck, M.Arash, L.Scarpa, M.Ketteridge, D.Hopwood, J.Plecko, B.Steiner, R.Whitley, C.Kaplan, P.Yu, Z.Swiedler, S.Decker, C.2009-11-032009-11-032008Molecular Genetics and Metabolism, 2008; 94(4):469-4751096-71921096-7206http://hdl.handle.net/2440/52128Copyright © 2008 Elsevier Inc. All rights reserved.<h4>Unlabelled</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>rhASB treatment up to 5 years results in sustained improvements in endurance and has an acceptable safety profile.enMPS VI Study GroupHumansMucopolysaccharidosis VIN-Acetylgalactosamine-4-SulfataseGlycosaminoglycansRecombinant ProteinsTreatment OutcomeWalkingFollow-Up StudiesMotor ActivityAdolescentAdultChildChild, PreschoolFemaleMaleLong-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-sulfataseJournal article002008163810.1016/j.ymgme.2008.04.0010002579350000142-s2.0-4694909335242654