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.

Trial registration: ClinicalTrials.gov NCT01515956.

Figures

Figure 1

Normalized urine keratan sulfate (uKS): mean percent change from baseline (N = 15). Normalized uKS is calculated as uKS divided by urine creatinine.

Figure 2

Normalized height/length and growth rate from baseline to week 52. (a) Mean standing height/lengtha z-score. Normalized standing height or length was computed using Centers for Disease Control normal values (17). (b) Mean standing height z-score at baseline and 52 wk for 12 patients ≥2 y of age included in this study (upper line) compared with 25 untreated subjects of 2–5 y of age included in the Morquio A Clinical Assessment Program (MorCAP) longitudinal natural history study at baseline and 52 wk (lower line). One of the 24 patients from the MorCAP study did not have a week 52 assessment and was excluded from this analysis. (c) Mean growth rate (per year) for standing height/lengtha z-score. Baseline rate calculation was based on observations up to 2 y prior to study entry. aLength was measured instead of standing height in subjects <2 y of age (N = 3).