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

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; <i>n</i> = 1), "average" (100-90; <i>n</i> = 4), and "low average" (85-80; <i>n</i> = 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; <i>n</i> = 1), "low average" (85-80; <i>n</i> = 3), and "very low" (69-43; <i>n</i> = 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.