Impact of long-term elosulfase alfa on activities of daily living in patients with Morquio A syndrome in an open-label, multi-center, phase 3 extension study

Christian J. Hendriksz*, Rossella Parini, Moeenaldeen D. AlSayed, Julian Raiman, Roberto Giugliani, John J. Mitchell, Barbara K. Burton, Norberto Guelbert, Fiona J. Stewart, Derralynn A. Hughes, Robert Matousek, Sara M. Hawley, Celeste Decker, Paul R. Harmatz

*Corresponding author for this work

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Background: Long-term safety and efficacy of elosulfase alfa enzyme replacement therapy (ERT) were assessed in 173 patients with Morquio A syndrome (mucopolysaccharidosis IVA) in a 96-week, open-label, multi-center, phase 3 extension study (MOR-005) of the pivotal 24-week, placebo-controlled study (MOR-004). Changes in efficacy endpoints were evaluated over 120 weeks, from MOR-004 baseline to MOR-005 week 96. We report the impact of ERT on activities of daily living (ADL) across three domains (mobility, self-care, and caregiver-assistance), as assessed by the Mucopolysaccharidosis Health Assessment Questionnaire (MPS-HAQ) after 72 and 120 weeks or approximately 1 and 2 years. Results: Mean baseline MPS-HAQ domain scores showed impairments in mobility, self-care, and independence. The MOR-005 intent-to-treat population (ITT; N = 169, including 158 with 2 years follow-up) showed sustained significant reductions (representing improvements) in mobility and self-care domain least square (LS) mean scores vs. baseline at 1 and 2 years and a non-significant decrease in the caregiver-assistance domain at 2 years. At week 120, LS mean (SE) changes from baseline were − 0.5 (0.1) for mobility (P = 0.002), − 0.4 (0.1) for self-care (P = 0.001), and − 1.0 (0.5) for caregiver-assistance (P = 0.06) (ITT population). Improvements in MPS-HAQ domain scores vs. baseline at 1 and 2 years were greater in patients continuously treated with the weekly dosing regimen than in the total MOR-005 population and statistically significant across domains. A comparable untreated cohort of patients from the Morquio A Clinical Assessment Program (MorCAP) natural history study (ITT population, N = 94, including 37 with 2 years follow-up) showed no improvement over 2 years, with two of the three domains worsening (LS mean (SE) changes from baseline: 0.3 (0.3) for mobility, 0.4 (0.2) for self-care, − 0.5 (0.8) for caregiver-assistance). Changes in LS mean scores vs. baseline were statistically significantly different between MOR-005 and MorCAP for the mobility domain (− 0.7 (SE 0.4), P = 0.0490) and the self-care domain (− 0.7 (SE 0.3), P = 0.0146) at 2 years. Conclusions: Together, these findings suggest that long-term elosulfase alfa ERT is associated with partial recovery of functional abilities, improving Morquio A patients' abilities to perform ADL. Trial registration: ClinicalTrials.gov NCT01415427. Registered 8 August 2011, retrospectively registered.

Original languageEnglish (US)
Pages (from-to)127-134
Number of pages8
JournalMolecular Genetics and Metabolism
Volume123
Issue number2
DOIs
StatePublished - Feb 2018

Keywords

  • Activities of daily living
  • Disability
  • Elosulfase alfa
  • Enzyme replacement therapy
  • MPS IVA
  • Morquio A syndrome

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

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    Hendriksz, C. J., Parini, R., AlSayed, M. D., Raiman, J., Giugliani, R., Mitchell, J. J., Burton, B. K., Guelbert, N., Stewart, F. J., Hughes, D. A., Matousek, R., Hawley, S. M., Decker, C., & Harmatz, P. R. (2018). Impact of long-term elosulfase alfa on activities of daily living in patients with Morquio A syndrome in an open-label, multi-center, phase 3 extension study. Molecular Genetics and Metabolism, 123(2), 127-134. https://doi.org/10.1016/j.ymgme.2017.11.015