# 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

## TL;DR

This study examines the effects of early enzyme replacement therapy on cognitive development in young children with Hunter syndrome.

## Contribution

The study provides evidence that early treatment with intrathecal idursulfase may stabilize cognitive development in young MPS II patients.

## Key findings

- BSID-III cognitive scores remained stable in most patients over 3 years of treatment.
- Cerebrospinal fluid glycosaminoglycan levels were significantly reduced after treatment initiation.
- Transition to DAS-II showed declining scores, but remained stable afterward in some patients.

## 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.