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

Objective The objective of this Phase 3 study was to confirm die efficacy and safety of recombinant human arylsulfatase B (rhASB) treatment of mucopolysaccharidosis type VI (MPS VI; Maroteaux-Lamy syndrome), a rare, fatal lysosomal storage disease with no effective treatment. Study design Thirty-nine patients with MPS VI were evaluated in a randomized double-blind, placebo-controlled, multicenter, multinational study for 24 weeks. The primary efficacy variable was the distance walked in a 12-minute walk test (12MWT). whereas the secondary efficacy variables were the number of stairs climbed in a 3-minute stair climb (3MSC) and the level of urinary glycosaminoglycan (GAG) excretion. All received drug in an open-label extensions period for an additional 24 weeks. Results After 24 week., patients receiving rhASB walked on average 92 meters (In) more in the 12MWT (p =.025) and 5.7 stairs per minute snore 3MSC (p =.053) than patients receiving placebo. Continued improvement was observed during the extension study. Urinary GAG declined by -227 +/- 18 mu g/mg more with rhASB than placebo (p <.001). Infusions were generally safe acid well tolerated. Patients exposed to drag experienced positive clinical benefit despite the presence of antibody to the protein. Conclusion rhASB significantly improves endurance, reduces GAG, and has in acceptable safety profile.