Hendriksz, CJ; Parini, R; AlSayed, MD; Raiman, J; Giugliani, R; Mitchell, JJ; Burton, BK; ... Harmatz, PR; + view all Hendriksz, CJ; Parini, R; AlSayed, MD; Raiman, J; Giugliani, R; Mitchell, JJ; Burton, BK; Guelbert, N; Stewart, FJ; Hughes, DA; Matousek, R; Hawley, SM; Decker, C; Harmatz, PR; - view fewer (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) pp. 127-134. 10.1016/j.ymgme.2017.11.015.

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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.

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