[Clinical study of enzyme replacement therapy with idursulfase]

Important advances have been made in enzyme replacement therapy in the treatment of lysosomal diseases over the last two decades. Here we review the initial ERT trial using idursulfase in Hunter syndrome (mucopolysaccharidosis type II) and we also examine relevant aspects of the use of this enzyme.

A preclinical trial in a knockout mouse showed a decrease in glycosaminoglycans, both in urine and in tissues, following treatment with idursulfase. In a randomised, double-blind, placebo-controlled clinical study in phase I/II conducted in 12 patients with Hunter syndrome, treatment with idursulfase displayed a good safety profile and also a decrease in the excretion of glycosaminoglycans and cases of visceromegaly. The 12 patients continued the study in an open manner for two years and favourable outcomes were also obtained. A recent randomised, double-blind, placebo-controlled, multi-centre and multinational study in phase II/III conducted with 96 patients with Hunter syndrome over one year showed that the administration of 0.5 mg/kg doses of idursulfase significantly improved the final 'combined' score, which was the sum of the changes in the percentage of predicted forced vital capacity and in the 6-minute walk test, in comparison to the response obtained with a placebo. This result was the same for the weekly treatment group (p = 0.0049) and the fortnightly group (p = 0.0416). Many of the secondary effectiveness parameters also improved significantly, especially in the weekly treatment group. Treatment with idursulfase was well tolerated, with side effects that were, generally speaking, mild or moderate. IgG antibodies were detected in up to 46.9% of the patients treated in the two groups, but no apparent relation with the side effects or the clinical response was observed.

Treatment with 0.5 mg/kg of idursulfase in weekly intravenous infusions is usually well tolerated and seems to improve the somatic symptoms in patients with mucopolysaccharidosis type II.