title: 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.
abstract: OBJECTIVE
  The objective of this Phase 3 study was to confirm the 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.
  
  
  METHODS
  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 patients received drug in an open-label extension period for an additional 24 weeks.
  
  
  RESULTS
  After 24 weeks, patients receiving rhASB walked on average 92 meters (m) more in the 12MWT (p=.025) and 5.7 stairs per minute more 3MSC (p=.053) than patients receiving placebo. Continued improvement was observed during the extension study. Urinary GAG declined by -227+/-18 microg/mg more with rhASB than placebo (p<.001). Infusions were generally safe and well tolerated. Patients exposed to drug experienced positive clinical benefit despite the presence of antibody to the protein.
  
  
  CONCLUSIONS
  rhASB significantly improves endurance, reduces GAG, and has an acceptable safety profile.
authors.affiliation: Children's Hospital & Research Center at Oakland, California 94609, USA, and Children's Hospital, University of Mainz, Germany. Pharmatz@mail.cho.org
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.forename: Ida
authors.initials: I
authors.lastname: Schwartz
authors.forename: Nathalie
authors.initials: N
authors.lastname: Guffon
authors.forename: Elisa Leão
authors.initials: EL
authors.lastname: Teles
authors.forename: M Clara Sá
authors.initials: MC
authors.lastname: Miranda
authors.forename: J Edmond
authors.initials: JE
authors.lastname: Wraith
authors.forename: Michael
authors.initials: M
authors.lastname: Beck
authors.forename: Laila
authors.initials: L
authors.lastname: Arash
authors.forename: Maurizio
authors.initials: M
authors.lastname: Scarpa
authors.forename: Zi-Fan
authors.initials: ZF
authors.lastname: Yu
authors.forename: Janet
authors.initials: J
authors.lastname: Wittes
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Berger
authors.forename: Mary S
authors.initials: MS
authors.lastname: Newman
authors.forename: Ann M
authors.initials: AM
authors.lastname: Lowe
authors.forename: Emil
authors.initials: E
authors.lastname: Kakkis
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Swiedler
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002648:Child; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006025:Glycosaminoglycans / Q000652:urine; D006801:Humans; D016014:Linear Models; D008297:Male; D009087:Mucopolysaccharidosis VI / Q000188:drug therapy*; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012449:Safety; D016138:Walking
chemical_list: D006025:Glycosaminoglycans; D011994:Recombinant Proteins; D020051:N-Acetylgalactosamine-4-Sulfatase