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

Christian J. Hendriksz*, Barbara Burton, Thomas R. Fleming, Paul Harmatz, Derralynn Hughes, Simon A. Jones, Shuan Pei Lin, Eugen Mengel, Maurizio Scarpa, Vassili Valayannopoulos, Roberto Giugliani, Peter Slasor, Debra Lounsbury, Wolfgang Dummer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

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.

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).

Original languageEnglish (US)
Pages (from-to)979-990
Number of pages12
JournalJournal of inherited metabolic disease
Volume37
Issue number6
DOIs
StatePublished - Oct 23 2014

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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