Safety and physiological effects of two different doses of elosulfase alfa in patients with morquio a syndrome: A randomized, double-blind, pilot study

Barbara K. Burton, Kenneth I. Berger, Gregory D. Lewis, Mark Tarnopolsky, Marsha Treadwell, John J. Mitchell, Nicole Muschol, Simon A. Jones, V. Reid Sutton, Gregory M. Pastores, Heather Lau, Rebecca Sparkes, Fred Genter, Adam J. Shaywitz, Paul Harmatz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

The primary treatment outcomes of a phase 2, randomized, double-blind, pilot study evaluating safety, physiological, and pharmacological effects of elosulfase alfa in patients with Morquio A syndrome are herewith presented. Patients aged ≥7 years and able to walk ≥200m in the 6-min walk test (6MWT) were randomized to elosulfase alfa 2.0 or 4.0mg/kg/week for 27 weeks. The primary objective was to evaluate the safety of both doses. Secondary objectives were to evaluate effects on endurance (6MWT and 3-min stair climb test [3MSCT]), exercise capacity (cardio-pulmonary exercise test [CPET]), respiratory function, muscle strength, cardiac function, pain, and urine keratan sulfate (uKS) levels, and to determine pharmacokinetic parameters. Twenty-five patients were enrolled (15 randomized to 2.0mg/kg/week and 10 to 4.0mg/kg/week). No new or unexpected safety signals were observed. After 24 weeks, there were no improvements versus baseline in the 6MWT, yet numerical improvements were seen in the 3MSCT with 4.0mg/kg/week. uKS and pharmacokinetic data suggested no linear relationship over the 2.0-4.0mg/kg dose range. Overall, an abnormal exercise capacity (evaluated in 10 and 5 patients in the 2.0 and 4.0mg/kg/week groups, respectively), impaired muscle strength, and considerable pain were observed at baseline, and there were trends towards improvements in all domains after treatment. In conclusion, preliminary data of this small study in a Morquio A population with relatively good endurance confirmed the acceptable safety profile of elosulfase alfa and showed a trend of increased exercise capacity and muscle strength and decreased pain.

Original languageEnglish (US)
Pages (from-to)2272-2281
Number of pages10
JournalAmerican Journal of Medical Genetics, Part A
Volume167
Issue number10
DOIs
StatePublished - Oct 1 2015

Keywords

  • Cardiopulmonary exercise test
  • Enzyme replacement therapy
  • GALNS protein
  • Human [supplementary concept]
  • Mucopolysaccharidosis IV
  • Muscle strength
  • Physical endurance
  • Respiratory function tests
  • Safety

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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