Evaluation of idursulfase for the treatment of mucopolysaccharidosis II (Hunter syndrome)

Introduction: Mucopolysaccharidosis II (MPS II) is an X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme iduronate-2-sulfatase (I2S), leading to an accumulation of glycosaminoglycans within lysosomes. Patients experience progressive, multisystemic disease, significant morbidity, and early mortality. Areas covered: Idursulfase, an I2S enzyme produced by recombinant DNA technology in a human cell line, was approved in 2006 in the United States and 2007 in the European Union for use in MPS II patients. The authors examine the published pharmacokinetic, safety, and efficacy data from the Phase I/II, Phase II/III, Phase II/III extension, and post-marketing surveillance studies of idursulfase. Expert opinion: Idursulfase is generally well tolerated and produces measurable clinical improvements in walking ability and statistically significant reductions in mean liver and spleen volumes and urinary glycosaminoglycan levels. The impact of anti-drug antibodies upon efficacy is unclear but is an active area of research. Treatment should be offered to MPS II patients with or without cognitive involvement, including females, as soon as possible after diagnosis. Patients with the severe (neuropathic) phenotype may receive certain somatic benefits from treatment, supporting a test of idursulfase treatment with clear expectations and discontinuation criteria discussed with the family before treatment initiation.