idursulfase-IT (TAK-609) / Takeda - LARVOL DELTA

An Extension Study of HGT-HIT-045 Evaluating Long-Term Safety and Clinical Outcomes of Idursulfase-IT in Conjunction With Elaprase in Pediatric Participants With Hunter Syndrome and Cognitive Impairment (clinicaltrials.gov) - P1/2 | N=15 | Completed | Sponsor: Takeda | N=25 ➔ 15

Enrollment change • Cognitive Disorders • Hunter Syndrome • Pediatrics

Extension Study of Idursulfase-IT Along With Elaprase in Children and Adults With Hunter Syndrome and Cognitive Impairment (clinicaltrials.gov) - P2/3 | N=6 | Active, not recruiting | Sponsor: Takeda | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2034 ➔ Jan 2029 | Trial primary completion date: Jan 2034 ➔ Jan 2029

Enrollment closed • Trial completion date • Trial primary completion date • Cognitive Disorders • Hunter Syndrome

A link between baseline neurofilament light chain and primary substrate accumulation in cerebrospinal fluid, and clinical outcomes in patients with MPS II from a phase 2/3 clinical trial and extension study of intrathecal idursulfase. (PubMed, Mol Genet Metab) - "TAK-609 is an intrathecal formulation of idursulfase (idursulfase-IT) that is delivered directly to the cerebrospinal fluid (CSF) of patients with neuronopathic MPS II to attenuate the neurocognitive decline. Taken together, this study establishes a clear link between genetic status, accumulation of primary substrate and circulating CSF NfL levels, allowing for bioanalytical stratification of patient outcomes in MPS II. TAKE-HOME MESSAGE: Baseline cerebrospinal neurofilament light chain levels correspond to the severity of iduronate-2-sulfatase gene (IDS) genotype, the degree of primary substrate burden and subsequent clinical outcomes in patients with neuronopathic mucopolysaccharidosis II, and can complement clinical assessments of disease heterogeneity."

Clinical data • Journal • P2/3 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases • CSF NfL • NEFL

Evaluation of early treatment with intravenous idursulfase and intrathecal idursulfase-IT on cognitive function in siblings with neuronopathic mucopolysaccharidosis II. (PubMed, J Inherit Metab Dis) - P=N/A, P2/3 | "Monthly idursulfase-IT was generally associated with a stabilization of cognitive function: DAS-II GCA and VABS-II ABC scores were higher at age-matched assessments in the majority of those who either received idursulfase-IT earlier than their sibling or who received idursulfase-IT versus no idursulfase-IT. These data suggest that early initiation of intrathecal enzyme replacement therapy may stabilize or slow cognitive decline in some patients with neuronopathic MPS II."

Journal • Alzheimer's Disease • Cognitive Disorders • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Study of Long Term Safety and Clinical Outcomes of Idursulfase IT and Elaprase Treatment in Pediatric Participants Who Have Completed Study HGT-HIT-094 (clinicaltrials.gov) - P2/3 | N=56 | Completed | Sponsor: Shire | Active, not recruiting ➔ Completed

Trial completion • Cognitive Disorders • Hunter Syndrome • Pediatrics

An Extension Study of HGT-HIT-045 Evaluating Long-Term Safety and Clinical Outcomes of Idursulfase-IT in Conjunction With Elaprase in Pediatric Participants With Hunter Syndrome and Cognitive Impairment (clinicaltrials.gov) - P1/2 | N=25 | Completed | Sponsor: Shire | Active, not recruiting ➔ Completed

Trial completion • Cognitive Disorders • Hunter Syndrome • Pediatrics

Clinical investigator perspectives on patient outcomes in children with neuronopathic mucopolysaccharidosis II during intrathecal idursulfase-IT treatment. (PubMed, Orphanet J Rare Dis) - P2/3 | "This qualitative analysis provides a snapshot of clinicians' considerations when evaluating treatment in patients with neuronopathic MPS II, compared with the expected decline in cognitive function in the absence of treatment. The results highlight the importance of robust assessment tools in treatment evaluation."

Journal • Alzheimer's Disease • Cognitive Disorders • Developmental Disorders • Hunter Syndrome • Lysosomal Storage Diseases • Mental Retardation • Metabolic Disorders • Pediatrics • Rare Diseases

Extension Study of Idursulfase-IT Along With Elaprase in Children and Adults With Hunter Syndrome and Cognitive Impairment (clinicaltrials.gov) - P2/3 | N=8 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting

Enrollment open • Cognitive Disorders • Hunter Syndrome

Caregiver experiences and observations of intrathecal idursulfase-IT treatment in a phase 2/3 trial in pediatric patients with neuronopathic mucopolysaccharidosis II. (PubMed, Orphanet J Rare Dis) - "This study revealed caregiver-reported improvements in children's MPS II symptoms and the impact of the disease on patients and their families. There was a trend for cognitive improvement and a reduction in severity of MPS II symptoms. After many years of extensive review and regulatory discussions of idursulfase-IT, the clinical trial data were found to be insufficient to meet the evidentiary standard to support regulatory filings."

Journal • P2 data • P2/3 data • P3 data • Alzheimer's Disease • Cognitive Disorders • Developmental Disorders • Hunter Syndrome • Mental Retardation • Pediatrics

An Extension Study of HGT-HIT-045 Evaluating Long-Term Safety and Clinical Outcomes of Idursulfase-IT in Conjunction With Elaprase in Pediatric Participants With Hunter Syndrome and Cognitive Impairment (clinicaltrials.gov) - P1/2 | N=25 | Active, not recruiting | Sponsor: Shire | Trial completion date: Dec 2023 ➔ Mar 2024 | Trial primary completion date: Dec 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • Cognitive Disorders • Hunter Syndrome • Pediatrics

Study of Long Term Safety and Clinical Outcomes of Idursulfase IT and Elaprase Treatment in Pediatric Participants Who Have Completed Study HGT-HIT-094 (clinicaltrials.gov) - P2/3 | N=56 | Active, not recruiting | Sponsor: Shire | Trial completion date: Dec 2023 ➔ Mar 2024 | Trial primary completion date: Dec 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • Cognitive Disorders • Hunter Syndrome • Pediatrics

A post hoc analysis of Projected Retained Ability Scores (PRAS) for the longitudinal assessment of cognitive functioning in patients with neuronopathic mucopolysaccharidosis II receiving intrathecal idursulfase-IT. (PubMed, Orphanet J Rare Dis) - P2/3 | "PRAS methodology may help to differentiate changes in cognitive development in MPS II, and therefore may represent a valuable addition to existing approaches for interpreting changes in cognitive scores over time."

Clinical • Journal • P2 data • Retrospective data • Alzheimer's Disease • Cognitive Disorders • Hunter Syndrome

Extension Study of Idursulfase-IT Along With Elaprase in Adults With Hunter Syndrome and Cognitive Impairment (clinicaltrials.gov) - P2/3 | N=8 | Not yet recruiting | Sponsor: Takeda

New P2/3 trial • Cognitive Disorders • Hunter Syndrome

Study of Long Term Safety and Clinical Outcomes of Idursulfase IT and Elaprase Treatment in Pediatric Participants Who Have Completed Study HGT-HIT-094 (clinicaltrials.gov) - P2/3 | N=49 | Active, not recruiting | Sponsor: Shire | Trial completion date: Jun 2023 ➔ Dec 2023 | Trial primary completion date: Jun 2023 ➔ Dec 2023

Trial completion date • Trial primary completion date • Cognitive Disorders • Hunter Syndrome • Pediatrics

Extension Study of HGT-HIT-045 Evaluating Long-Term Safety and Clinical Outcomes of Idursulfase-IT in Conjunction With Elaprase in Pediatric Participants With Hunter Syndrome and Cognitive Impairment (clinicaltrials.gov) - P1/2 | N=25 | Active, not recruiting | Sponsor: Shire | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Cognitive Disorders • Hunter Syndrome • Pediatrics

Post-trial Access Program of Idursulfase-IT Along With Elaprase in Children With Hunter Syndrome (clinicaltrials.gov) - P=N/A | N=N/A | Available | Sponsor: Takeda

New trial • Cognitive Disorders • Hunter Syndrome • Pediatrics

Study of Long Term Safety and Clinical Outcomes of Idursulfase IT and Elaprase Treatment in Pediatric Participants Who Have Completed Study HGT-HIT-094 (clinicaltrials.gov) - P2/3 | N=49 | Active, not recruiting | Sponsor: Shire | Trial completion date: Jun 2027 ➔ Jun 2023 | Trial primary completion date: Jun 2027 ➔ Jun 2023

Clinical data • Trial completion date • Trial primary completion date • Cognitive Disorders • Hunter Syndrome • Pediatrics

Intrathecal idursulfase-IT in patients with neuronopathic mucopolysaccharidosis II: Results from a phase 2/3 randomized study. (PubMed, Mol Genet Metab) - P2/3 | "These data suggest potential benefits of idursulfase-IT in the treatment of cognitive impairment in some patients with neuronopathic MPS II. After many years of extensive review and regulatory discussions, the data were found to be insufficient to meet the evidentiary standard to support regulatory filings."

Clinical • Journal • P2/3 data • Alzheimer's Disease • Cognitive Disorders • Hunter Syndrome

Long-term open-label extension study of the safety and efficacy of intrathecal idursulfase-IT in patients with neuronopathic mucopolysaccharidosis II. (PubMed, Mol Genet Metab) - P2/3 | "These long-term data further suggest the benefits of idursulfase-IT in the treatment of neurocognitive dysfunction in some patients with MPS II. After many years of extensive review and regulatory discussions, the data were found to be insufficient to meet the evidentiary standard to support regulatory filings."

Journal • Alzheimer's Disease • Cognitive Disorders • Hunter Syndrome

Long-term open-label phase I/II extension study of intrathecal idursulfase-IT in the treatment of neuronopathic mucopolysaccharidosis II. (PubMed, Genet Med) - P1/2 | "These long-term results support the clinical development of idursulfase-IT for patients with MPS II with cognitive impairment."

Journal • P1/2 data • Alzheimer's Disease • Cognitive Disorders • Hunter Syndrome • Pediatrics

Extension Study of HGT-HIT-045 Evaluating Long-Term Safety and Clinical Outcomes of Idursulfase-IT in Conjunction With Elaprase in Pediatric Participants With Hunter Syndrome and Cognitive Impairment (clinicaltrials.gov) - P1/2; N=25; Active, not recruiting; Sponsor: Shire; Trial completion date: Jul 2021 ➔ Dec 2022; Trial primary completion date: Jul 2021 ➔ Dec 2022

Clinical • Clinical data • Trial completion date • Trial primary completion date • Cognitive Disorders • Hunter Syndrome • Pediatrics

Study of Long Term Safety and Clinical Outcomes of Idursulfase IT and Elaprase Treatment in Pediatric Participants Who Have Completed Study HGT-HIT-094 (clinicaltrials.gov) - P2/3; N=49; Active, not recruiting; Sponsor: Shire; Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Cognitive Disorders • Hunter Syndrome • Pediatrics

Study of Long Term Safety and Clinical Outcomes of Idursulfase IT and Elaprase Treatment in Pediatric Participants Who Have Completed Study HGT-HIT-094 (clinicaltrials.gov) - P2/3; N=49; Enrolling by invitation; Sponsor: Shire; Trial completion date: Jul 2025 ➔ Jun 2027; Trial primary completion date: Jul 2025 ➔ Jun 2027

Clinical • Clinical data • Trial completion date • Trial primary completion date • MRI

Study of Long Term Safety and Clinical Outcomes of Idursulfase IT and Elaprase Treatment in Pediatric Participants Who Have Completed Study HGT-HIT-094 (clinicaltrials.gov) - P2/3; N=49; Enrolling by invitation; Sponsor: Shire; Trial completion date: Sep 2022 ➔ Jul 2025; Trial primary completion date: Sep 2022 ➔ Jul 2025

Clinical • Clinical data • Trial completion date • Trial primary completion date