Long-term, open-labeled extension study of idursulfase in the treatment of Hunter syndrome.

PURPOSE: This study evaluated the safety and effectiveness of long-term enzyme replacement therapy with idursulfase (recombinant human iduronate-2-sulfatase) in patients with Hunter syndrome. METHODS: All 94 patients who completed a 53-week double-blinded study of idursulfase enrolled in this open-labeled extension study and received intravenous idursulfase at a dose of 0.5 mg/kg weekly for 2 years, and clinical outcomes and safety were assessed. RESULTS: No change in percent predicted forced vital capacity was seen, but absolute forced vital capacity demonstrated sustained improvement and was increased 25.1% at the end of the study. Statistically significant increases in 6-minute walking test distance were observed at most time points. Mean liver and spleen volumes remained reduced throughout the 2-year extension study. Mean joint range of motion improved for the shoulder and remained stable in other joints. Both the parent- and child-assessed Child Health Assessment Questionnaire Disability Index Score demonstrated significant improvement. Infusion-related adverse events occurred in 53% of patients and peaked at Month 3 of treatment and declined thereafter. Neutralizing IgG antibodies were detected in 23% of patients and seemed to attenuate the improvement in pulmonary function. CONCLUSIONS: Weekly infusions of idursulfase result in sustained clinical improvement during 3 years of treatment.

A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome).

PURPOSE: To evaluate the safety and efficacy of recombinant human iduronate-2-sulfatase (idursulfase) in the treatment of mucopolysaccharidosis II. METHODS: Ninety-six mucopolysaccharidosis II patients between 5 and 31 years of age were enrolled in a double-blind, placebo-controlled trial. Patients were randomized to placebo infusions, weekly idursulfase (0.5 mg/kg) infusions or every-other-week infusions of idursulfase (0.5 mg/kg). Efficacy was evaluated using a composite endpoint consisting of distance walked in 6 minutes and the percentage of predicted forced vital capacity based on the sum of the ranks of change from baseline. RESULTS: Patients in the weekly and every-other-week idursulfase groups exhibited significant improvement in the composite endpoint compared to placebo (P = 0.0049 for weekly and P = 0.0416 for every-other-week) after one year. The weekly dosing group experienced a 37-m increase in the 6-minute-walk distance (P = 0.013), a 2.7% increase in percentage of predicted forced vital capacity (P = 0.065), and a 160 mL increase in absolute forced vital capacity (P = 0.001) compared to placebo group at 53 weeks. Idursulfase was generally well tolerated, but infusion reactions did occur. Idursulfase antibodies were detected in 46.9% of patients during the study. CONCLUSION: This study supports the use of weekly infusions of idursulfase in the treatment of mucopolysaccharidosis II.