title: Efficacy and safety of enzyme replacement therapy with BMN 110 (elosulfase alfa) for Morquio A syndrome (mucopolysaccharidosis IVA): a phase 3 randomised placebo-controlled study.
abstract: OBJECTIVE
  To assess the efficacy and safety of enzyme replacement therapy (ERT) with BMN 110 (elosulfase alfa) in patients with Morquio A syndrome (mucopolysaccharidosis IVA).
  
  
  METHODS
  Patients with Morquio A aged ≥5 years (N = 176) were randomised (1:1:1) to receive elosulfase alfa 2.0 mg/kg/every other week (qow), elosulfase alfa 2.0 mg/kg/week (weekly) or placebo for 24 weeks in this phase 3, double-blind, randomised study. The primary efficacy measure was 6-min walk test (6MWT) distance. Secondary efficacy measures were 3-min stair climb test (3MSCT) followed by change in urine keratan sulfate (KS). Various exploratory measures included respiratory function tests. Patient safety was also evaluated.
  
  
  RESULTS
  At week 24, the estimated mean effect on the 6MWT versus placebo was 22.5 m (95 % CI 4.0, 40.9; P = 0.017) for weekly and 0.5 m (95 % CI -17.8, 18.9; P = 0.954) for qow. The estimated mean effect on 3MSCT was 1.1 stairs/min (95 % CI -2.1, 4.4; P = 0.494) for weekly and -0.5 stairs/min (95 % CI -3.7, 2.8; P = 0.778) for qow. Normalised urine KS was reduced at 24 weeks in both regimens. In the weekly dose group, 22.4 % of patients had adverse events leading to an infusion interruption/discontinuation requiring medical intervention (only 1.3 % of all infusions in this group) over 6 months. No adverse events led to permanent treatment discontinuation.
  
  
  CONCLUSIONS
  Elosulfase alfa improved endurance as measured by the 6MWT in the weekly but not qow dose group, did not improve endurance on the 3MSCT, reduced urine KS, and had an acceptable safety profile.
authors.affiliation: Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UK, chris.hendriksz@srft.nhs.uk.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Hendriksz
authors.forename: Barbara
authors.initials: B
authors.lastname: Burton
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Fleming
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
authors.forename: Derralynn
authors.initials: D
authors.lastname: Hughes
authors.forename: Simon A
authors.initials: SA
authors.lastname: Jones
authors.forename: Shuan-Pei
authors.initials: SP
authors.lastname: Lin
authors.forename: Eugen
authors.initials: E
authors.lastname: Mengel
authors.forename: Maurizio
authors.initials: M
authors.lastname: Scarpa
authors.forename: Vassili
authors.initials: V
authors.lastname: Valayannopoulos
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.forename: Peter
authors.initials: P
authors.lastname: Slasor
authors.forename: Debra
authors.initials: D
authors.lastname: Lounsbury
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dummer
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002811:Chondroitinsulfatases / Q000627:therapeutic use*; D004311:Double-Blind Method; D056947:Enzyme Replacement Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D007632:Keratan Sulfate / Q000652:urine*; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D009085:Mucopolysaccharidosis IV / Q000188:drug therapy*; D035583:Rare Diseases / Q000188:drug therapy*; D016896:Treatment Outcome; D016138:Walking; D055815:Young Adult
chemical_list: D007632:Keratan Sulfate; D002811:Chondroitinsulfatases; C102295:GALNS protein, human