Safety and clinical activity of elosulfase alfa in pediatric patients with Morquio A syndrome (mucopolysaccharidosis IVA) less than 5 y.
BACKGROUND
Previous studies have shown that elosulfase alfa has a favorable efficacy/safety profile in Morquio A patients aged ≥5 y. This study evaluated safety and impact on urine keratan sulfate (uKS) levels and growth velocity in younger patients.


METHODS
Fifteen Morquio A patients aged <5 y received elosulfase alfa 2.0 mg/kg/week for 52 wk during the primary treatment phase of a phase II, open-label, multinational study. Primary endpoint was safety and tolerability; secondary endpoints were change in uKS and growth velocity over 52 wk.


RESULTS
All 15 patients completed the primary treatment phase. Six of 743 infusions (0.8%) administered led to adverse events (AEs) requiring infusion interruption and medical intervention. Eleven patients (73.3%) had ≥1 study drug-related AE, mostly infusion-associated reactions. Mean z-score growth rate per year numerically improved from -0.6 at baseline to -0.4 at week 52. Comparison to untreated subjects of similar age in the Morquio A Clinical Assessment Program study showed a smaller decrease in height z-scores for treated than for untreated patients. Mean percent change from baseline in uKS was -30.2% at 2 wk and -43.5% at 52 wk.


CONCLUSIONS
Early intervention with elosulfase alfa is well-tolerated and produces a decrease in uKS and a trend toward improvement in growth.
Willink Unit, Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester Academic Health Sciences Centre, University of Manchester, Central Manchester University Hospital National Health Service Foundation Trust, Manchester, UK.
Simon A
SA
Jones
North Shore LIJ Health System, Department of Pediatrics, Manhasset, New York.
Martin
M
Bialer
Azienda Ospedaliera San Gerardo, Unita Operativa Semplice Malattie Metaboliche Rare, Monza, Italy.
Rossella
http://orcid.org/0000-0003-4505-1306
R
Parini
BioMarin Pharmaceutical Inc., Novato, California.
Ken
K
Martin
BioMarin Pharmaceutical Inc., Novato, California.
Hui
H
Wang
BioMarin Pharmaceutical Inc., Novato, California.
Ke
K
Yang
BioMarin Pharmaceutical Inc., Novato, California.
Adam J
AJ
Shaywitz
UCSF Benioff Children's Hospital Oakland, Department of Gastroenterology, Oakland, California.
Paul
P
Harmatz
D000367:Age Factors; D015415:Biomarkers / Q000652:urine; D001827:Body Height / Q000187:drug effects; D002657:Child Development / Q000187:drug effects; D002675:Child, Preschool; D002811:Chondroitinsulfatases / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D061345:Early Medical Intervention; D056947:Enzyme Replacement Therapy / Q000009:adverse effects; D005060:Europe; D005260:Female; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D007632:Keratan Sulfate / Q000652:urine; D008297:Male; D009085:Mucopolysaccharidosis IV / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology / Q000652:urine; D011994:Recombinant Proteins / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom
D015415:Biomarkers; D011994:Recombinant Proteins; D007632:Keratan Sulfate; D002811:Chondroitinsulfatases; C102295:GALNS protein, human