Mucopolysaccharidosis II (MPS 11; Hunter syndrome) is a rare, progressive lysosomal storage disease caused by pathogenic variants in the iduronate-2-sulfatase gene (IDS). Cognitive impairment (neuronopathic disease) affects approximately two-thirds of patient s. A phase 2/3 trial (NCT02055118) and exten sio n (NCT02412787) showed a possibl e cogniti ve benefit of treatment with intrathecal recombinant iduronate-2- sul fatase (idursulfase-lT) in patients with neuronopathic MPS II <6 years old at baseline. Semi-structured interviews were conducted ?: 36 months after Phase 2/ 3 trial enrolment with nine clinical investigator s who enrolled 56 patient s treated with idursulfase-lT in the exten sion st udy. The aim was to evaluate the overall treatment effect s observed by the clinicians that may not have been full y captured by the trial outcome measur es. Investigators provided opinion-based assessments of the effects of idursul fase-lT, both on their own patients and in a blinded review of data from other patients in the study with large IDS deletions. They identified limitations of the Differential Ability Scales-II and Vineland Adaptive Behavior Scales-II instruments in this population and reported additional clinical impressions of their own patients that were reflective of the disease course beyond neurocognitive scores alone. In total, 49/ 56 patients were rated by investi gat ors as having disease that was improved/ improvin g, stabilised or slo wing progression while receiving idursulfase-lT. Overall, in vesti gators p rovided po siti ve opinion-based evaluati ons of the cogniti ve benefits of idursulfase-lT in MPS II versus outcomes expected without treatment , and reinforced the need for early treatment initiation in patients with neuronopathic MPS II. St udy and writing funded by Takeda; intended for HCPs.
