Impact of long-term elosulfase alfa treatment on respiratory function in patients with Morquio A syndrome

• Published in: Journal of inherited metabolic disease 2016-11, Vol.39 (6), p.839-847
• Main Authors: Hendriksz, Christian J., Berger, Kenneth I., Parini, Rossella, AlSayed, Moeenaldeen D., Raiman, Julian, Giugliani, Roberto, Mitchell, John J., Burton, Barbara K., Guelbert, Norberto, Stewart, Fiona, Hughes, Derralynn A., Matousek, Robert, Jurecki, Elaina, Decker, Celeste, Harmatz, Paul R.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Biochemistry; Child; Child, Preschool; Chondroitinsulfatases - therapeutic use; Double-Blind Method; Enzyme Replacement Therapy - methods; Female; Forced Expiratory Volume - drug effects; Human Genetics; Humans; Internal Medicine; Long-Term Care; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Mucopolysaccharidosis IV - drug therapy; Original; Original Article; Pediatrics; Respiration - drug effects; Respiratory Function Tests - methods; Young Adult
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1007/s10545-016-9973-6

Objective To present long-term respiratory function outcomes from an open-label, multi-center, phase 3 extension study (MOR-005) of elosulfase alfa enzyme replacement therapy (ERT) in patients with Morquio A syndrome. Methods In part 1 of MOR-005, patients initially randomized to ERT in the 24-week pivotal study (MOR-004) remained on their regimen (2.0 mg/kg/week or every other week); placebo patients were re-randomized to one of the two regimens. During part 2, all patients received elosulfase alfa 2.0 mg/kg/week. Respiratory function was one of the efficacy endpoints evaluated in MOR-005. Change from MOR-004 baseline to 120 weeks of treatment for the combined population was determined and compared with results from untreated patients from a Morquio A natural history study (MorCAP). Results Maximum voluntary ventilation (MVV) improved up to week 72 and then stabilized; forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV 1 ) increased continuously over 120 weeks. Mean increases in the modified per-protocol population was 9.2 % for FVC, 8.8 % for FEV 1 , and 6.1 % for MVV after 120 weeks. All patients ≤14 years showed respiratory improvements, presumably in part related to growth; however, these were greater in treated patients. For those >14 years, treated patients showed improvements, while deterioration occurred in untreated. Altogether, the improvements were significantly greater ( P