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
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Authors
Hendriksz, Christian J.
Parini, Rossella
AlSayed, Moeenaldeen D.
Raiman, Julian
Giugliani, Roberto
Mitchell, John J.
Burton, Barbara K.
Guelbert, Norberto
Stewart, Fiona J.
Hughes, Derralynn A.
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Publisher
Elsevier
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 selfcare
(P =0.001), and −1.0 (0.5) for caregiver-assistance (P= 0.06) (ITT population). Improvements in MPSHAQ
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.
Description
Supplementary file 1. Items in the MPS Health Assessment Questionnaire (MPS-HAQ).
Supplementary file 2. Items in the MPS Health Assessment Questionnaire (MPS-HAQ) (A) showing impairment in the self-care and mobility domains (score ≥ 1) and the caregiver-assistance domain (score > 1) in ≥ 70% of patients and (B) scored “unable to complete” or “complete assistance required” in ≥ 15% of patients in the MOR-005 ITT population.
Supplementary file 3. Baseline demographics of patients from the MOR-005 intent-to-treat (ITT) and modified per-protocol (MPP) population and comparable patients from the MorCAP natural history study included in the 2-year analysis.
Supplementary file 2. Items in the MPS Health Assessment Questionnaire (MPS-HAQ) (A) showing impairment in the self-care and mobility domains (score ≥ 1) and the caregiver-assistance domain (score > 1) in ≥ 70% of patients and (B) scored “unable to complete” or “complete assistance required” in ≥ 15% of patients in the MOR-005 ITT population.
Supplementary file 3. Baseline demographics of patients from the MOR-005 intent-to-treat (ITT) and modified per-protocol (MPP) population and comparable patients from the MorCAP natural history study included in the 2-year analysis.
Keywords
Morquio A syndrome, Elosulfase alfa, Disability, Activities of daily living (ADL), Enzyme replacement therapy (ERT), Disease, Endurance, Safety, Respiratory function, Mucopolysaccharidosis IVA, Mucopolysaccharidosis (MPS)
Sustainable Development Goals
Citation
Hendriksz, C.J., Parini, R., AlSayed, M.D. et al. 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, vol. 123, no. 2, pp. 127-134.