Safety and clinical activity of elosulfase alfa in pediatric patients with Morquio A syndrome (mucopolysaccharidosis IVA) less than 5 y.

Abstract

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.

CONCLUSION:

Early intervention with elosulfase alfa is well-tolerated and produces a decrease in uKS and a trend toward improvement in growth.

• Authors: Simon A Jones, Martin Bialer, Rossella Parini, Ken Martin, Hui Wang, Ke Yang, Adam J Shaywitz, Paul Harmatz
• Journal: Pediatric research (Pediatr Res) Vol. 78 Issue 6 Pg. 717-22 (Dec 2015) ISSN: 1530-0447 [Electronic] United States
• PMID: 26331768 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Recombinant Proteins
• Keratan Sulfate
• Chondroitinsulfatases
• GALNS protein, human

Topics

• Age Factors
• Biomarkers (urine)
• Body Height (drug effects)
• Child Development (drug effects)
• Child, Preschool
• Chondroitinsulfatases (administration & dosage, adverse effects)
• Drug Administration Schedule
• Early Medical Intervention
• Enzyme Replacement Therapy (adverse effects)
• Europe
• Female
• Humans
• Infant
• Infusions, Intravenous
• Keratan Sulfate (urine)
• Male
• Mucopolysaccharidosis IV (diagnosis, drug therapy, enzymology, physiopathology, urine)
• Recombinant Proteins (administration & dosage)
• Time Factors
• Treatment Outcome
• United Kingdom