Izcargo (pabinafusp alfa) / JCR Pharma, Takeda - LARVOL DELTA

JCR Pharmaceuticals to Present at the 21st Annual WORLDSymposium 2025 (Businesswire) - "The first presentation will spotlight JR-479, an investigational BBB-penetrating β-Hexosaminidase A (rDNA origin) enzyme replacement therapy (ERT) that JCR is developing for the treatment of people with GM2 gangliosidoses....The second presentation will highlight JCR’s lead product candidate, JR-141 (pabinafusp alfa, intravenous infusion), a recombinant fusion protein consisting of a humanized anti-transferrin receptor antibody and iduronate-2-sulfatase for the treatment of people with mucopolysaccharidosis type II (MPS II, or Hunter syndrome)."

Clinical data • Preclinical • Hunter Syndrome • Lysosomal Storage Diseases

Heparan sulfate in cerebrospinal fluid as a biomarker to assess disease severity and for treatment monitoring in patients with Mucopolysaccharidosis Type II: a position statement. (PubMed, Orphanet J Rare Dis) - "CSF HS levels may help differentiate between neuronopathic and non-neuronopathic forms of MPS II, with preliminary observations suggesting a potential threshold around 4,000 ng/mL when HS quantification is performed using the same method described in clinical studies of pabinafusp alfa...The same monitoring scheme is recommended for patients with the attenuated MPS II phenotype, however, after two years of treatment, the physician may elect to perform regular neurocognitive evaluations instead of measuring HS in CSF. Lastly, the authors reinforced the importance of evaluating adherence to treatment, including interruptions, to provide a more meaningful assessment of the treatment's real-world impact and to determine the ideal timing of CSF collection for therapeutic monitoring."

Biomarker • Journal • Hunter Syndrome

GENE THERAPY FOR GM1 GANGLIOSIDOSIS MEDIATED BY AAV VECTOR CARRYING BBB-PENETRABLE ENZYME (SSIEM 2024) - "Recently, we reported an anti-transferrin receptor antibody (TfR) fused enzyme that could cross the BBB and formulated as Pabinafusp alfa for MPS II enzyme replacement therapy... We concluded that fusion enzyme expressed in the liver was secreted into the blood and efficiently penetrated the brain, resulting in the normalization of the accumulated GM1 ganglioside in the CNS, improvement of neurological function, and extension of lifespan in GM1 mice. Therefore, i.v. of Tβgal is an effective approach for the treatment of GM1 at a low viral dose."

Gene therapy • Gene Therapies • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

NEUROCOGNITIVE DEVELOPMENTS IN SIBLINGS WITH NEUROPATHIC MPS-II RECEIVING CONVENTIONAL AND NOVEL ENZYME REPLACEMENT THERAPIES: AN UPDATE (SSIEM 2024) - "Two drugs that can address these problems, pabinafusp alfa (PA) for BBB-penetrating intravenous ERT, and idursulfase beta for intracerebroventricular (ICV) ERT, were approved in 2021 for general use in Japan... These observations suggest that novel ERT is clinically effective in addressing neuronopathy in MPS II and helping maintain or improve neurocognitive development, especially when introduced as early as feasible following diagnosis."

CNS Disorders • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

GENE THERAPY FOR GM1 GANGLIOSIDOSIS MEDIATED BY AAV VECTOR CARRYING BBB-PENETRABLE ENZYME (SSIEM 2024) - "Recently, we reported an anti-transferrin receptor antibody (TfR) fused enzyme that could cross the BBB and formulated as Pabinafusp alfa for MPS II enzyme replacement therapy... We concluded that fusion enzyme expressed in the liver was secreted into the blood and efficiently penetrated the brain, resulting in the normalization of the accumulated GM1 ganglioside in the CNS, improvement of neurological function, and extension of lifespan in GM1 mice. Therefore, i.v. of Tβgal is an effective approach for the treatment of GM1 at a low viral dose."

Gene therapy • Gene Therapies • Genetic Disorders • Lysosomal Storage Diseases • Rare Diseases

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

Analysis of caregiver perspectives on patients with mucopolysaccharidosis II treated with pabinafusp alfa: results of qualitative interviews in Japan. (PubMed, Orphanet J Rare Dis) - "Caregivers' perspectives in this study demonstrate treatment satisfaction and improvement in various aspects of quality of life following therapy with pabinafusp alfa. These findings enhance understanding of pabinafusp alfa's potential benefits in treating MPS II and contribute to defining MPS II-specific outcome measures for future clinical trials."

Interview • Journal • Fatigue • Hunter Syndrome • Metabolic Disorders • Musculoskeletal Diseases

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

Neurodevelopmental status and adaptive behavior of pediatric patients with mucopolysaccharidosis II: a longitudinal observational study. (PubMed, Orphanet J Rare Dis) - P=N/A | "Some patients with MPS II had rapid declines in cognitive ability, whereas others remained relatively stable after an initial decline. These insights provide a basis for more detailed analyses of different patient subgroups, which may enhance the definition and understanding of factors that influence cognitive and adaptive function in MPS II."

Journal • Observational data • Retrospective data • Alzheimer's Disease • Cognitive Disorders • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Pediatrics • Rare Diseases

Transferrin Receptor-Targeted Iduronate-2-sulfatase Penetrates the Blood-Retinal Barrier and Improves Retinopathy in Mucopolysaccharidosis II Mice. (PubMed, Mol Pharm) - "In this study, we show that a fusion protein, designated pabinafusp alfa, consisting of an antihuman transferrin receptor antibody and iduronate-2-sulfatase (IDS), crosses the BRB and reaches the retina in a murine model of MPS II...In contrast, recombinant nonfused IDS failed to reach the retina and hardly affected the retinal disease. These results support the hypothesis that transferrin receptor-targeted IDS can penetrate the BRB, thereby ameliorating retinal dysfunction in MPS II."

Journal • Preclinical • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Ophthalmology • Rare Diseases • Retinal Disorders

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

An integrated analysis to evaluate neurocognitive function in individuals with mucopolysaccharidosis II (MPS II) following long-term treatment with pabinafusp alfa (SSIEM 2023) - P2/3, P3 | "Early treatment initiation and a relatively preserved DQ at onset of treatment with pabinafusp alfa was associated with favorable cognitive outcomes in patients with neuronopathic MPS II. Stabilization of cognitive function was observed in neuronopathic patients who started treatment later and had a DQ70; a small number also showed improvements. These data suggest that treatment with pabinafusp alfa may be of therapeutic benefit for MPS II patients with neurological symptoms."

Clinical • Hunter Syndrome

An integrated analysis to evaluate neurocognitive function in individuals with mucopolysaccharidosis II (MPS II) following long-term treatment with pabinafusp alfa (SSIEM 2023) - No abstract available

Clinical • Hunter Syndrome

An integrated analysis to evaluate neurocognitive function in individuals with mucopolysaccharidosis II (MPS II) following long-term treatment with pabinafusp alfa (SSIEM 2023) - No abstract available

Clinical • Hunter Syndrome

An integrated analysis to evaluate neurocognitive function in individuals with mucopolysaccharidosis II (MPS II) following long-term treatment with pabinafusp alfa (SSIEM 2023) - No abstract available

Clinical • Hunter Syndrome

An Extension Study of JR-141-BR21 in Patients With Mucopolysaccharidosis II (clinicaltrials.gov) - P2 | N=19 | Active, not recruiting | Sponsor: JCR Pharmaceuticals Co., Ltd. | Trial completion date: Dec 2026 ➔ Mar 2024 | Trial primary completion date: Dec 2026 ➔ Mar 2024

Trial completion date • Trial primary completion date • Hunter Syndrome

A Phase III Study of JR-141 in Patients With Mucopolysaccharidosis II (STARLIGHT) (clinicaltrials.gov) - P3 | N=80 | Recruiting | Sponsor: JCR Pharmaceuticals Co., Ltd. | Trial completion date: Oct 2026 ➔ Jan 2026 | Trial primary completion date: Oct 2026 ➔ Jan 2026

Trial completion date • Trial primary completion date • Hunter Syndrome

A Phase III Study of JR-141 in Patients With Mucopolysaccharidosis II (STARLIGHT) (clinicaltrials.gov) - P3 | N=80 | Recruiting | Sponsor: JCR Pharmaceuticals Co., Ltd. | Trial completion date: Jan 2026 ➔ Oct 2026 | Trial primary completion date: Jan 2026 ➔ Oct 2026

Trial completion date • Trial primary completion date • Hunter Syndrome

Innovative Mechanisms of Pre-Market Authorization Access for Rare Diseases in Brazil. a Case Study of Pabinafusp-Alfa for Mucopolysaccharidosis Type II (ISPOR 2023) - "Innovative access alternatives can provide faster access to treatments for patients with unmet needs, especially with orphan diseases. Other alternatives include a) access through clinical studies, with execution/development aligned with healthcare managers and linked with potential future access strategies; b) risk sharing at regulatory level, considering the uncertainties in effectiveness and possibly market withdrawal and/or reimbursement to the system in case of negative results; c) pre-delivery, with subsequent payment only if the results of the clinical study are positive."

Clinical • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Gene Therapy for GM1 Gangliosidosis Mediated by AAV Vector Carrying BBB-Penetrable Enzyme (ASGCT 2023) - "Recently, we reported an anti-transferrin receptor antibody (TfR) fused enzyme that could cross the BBB and formulated as Pabinafusp Alfa for MPS II enzyme replacement therapy (ERT)...The amount of GM1-ganglioside in the group treated with low dose of TfR-βgal downed in half and with high doses of TfR-βgal was found to be at the same level as in wild-type mice.Furthermore, TfR-βgal treated mice exhibited improvements in some of the behavioral experiments such as open field test. These results show that intravenous administration of AAV- TfR-βgal is an effective approach for the treatment of GM1 at such a low viral dose."

Gene therapy • Gene Therapies • Genetic Disorders • Infectious Disease • Lysosomal Storage Diseases • Rare Diseases • GLB1

An Extension Study of JR-141 to Evaluate the Long-term Safety and Efficacy in Mucopolysaccharidosis Type II (Hunter Syndrome) Male Subjects (clinicaltrials.gov) - P3 | N=80 | Enrolling by invitation | Sponsor: JCR Pharmaceuticals Co., Ltd. | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • Hunter Syndrome

An Extension Study of JR-141 to Evaluate the Long-term Safety and Efficacy in Mucopolysaccharidosis Type II (Hunter Syndrome) Male Subjects (clinicaltrials.gov) - P3 | N=80 | Not yet recruiting | Sponsor: JCR Pharmaceuticals Co., Ltd.

New P3 trial • Hunter Syndrome

Impact of the Timing of Enzyme Replacement Therapy Initiation and Cognitive Impairment Status on Outcomes for Patients with Mucopolysaccharidosis II (MPS II) in the United States: A Retrospective Chart Review. (PubMed, J Health Econ Outcomes Res) - "Cognitively impaired patients experience a particularly high disease burden and HRU. Patient care could be improved with early cognitive assessments and the development of treatments that address cognitive decline."

Journal • Retrospective data • Review • Alzheimer's Disease • Cognitive Disorders • Developmental Disorders • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

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