Intrathecal idursulfase‐ IT in children younger than 3 years with neuronopathic mucopolysaccharidosis II in a single‐arm, open‐label, phase 2/3 substudy and extension

Abstract Data from a phase 2/3, randomized, controlled, open‐label, multicenter trial in children with neuronopathic mucopolysaccharidosis II (MPS II; Hunter syndrome) older than 3 years suggested a benefit of intrathecal idursulfase‐IT on cognitive functioning in some patients. We describe a separate, parallel, open‐label, single‐arm, 52‐week substudy of the same trial (NCT02055118) that investigated idursulfase‐IT in children with MPS II younger than 3 years at enrollment and Bayley Scales of Infant and Toddler Development (BSID‐III) quotient 55–85. This report describes a prespecified analysis of nine patients (aged 1.4–3.0 years) who had received 3‐years' treatment with idursulfase‐IT. BSID‐III cognitive composite scores generally remained relatively stable over time. At the last available assessment, scores were “high average” (110; n = 1), “average” (100–90; n = 4), and “low average” (85–80; n = 4). Eight patients transitioned to the Differential Ability Scales (DAS‐II) after ages ≥42 months, and scores decreased for all patients when the instrument for assessing cognitive function changed. However, DAS‐II General Conceptual Ability scores were relatively stable for the remainder of the follow‐up. At the last available assessment, scores were “average” (106; n = 1), “low average” (85–80; n = 3), and “very low” (69–43; n = 4). Cerebrospinal fluid concentrations of total glycosaminoglycans were markedly reduced from baseline levels (mean range 1278 429–2660 ng/mL) by week 16 and remained low thereafter. Data suggest early enzyme replacement therapy may stabilize cognitive development or slow the progression of cognitive impairment in young patients with neuronopathic MPS II.