- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma
Biomarker, Journal: 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 Central) - Nov 27, 2024
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.
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma
GENE THERAPY FOR GM1 GANGLIOSIDOSIS MEDIATED BY AAV VECTOR CARRYING BBB-PENETRABLE ENZYME (Poster Room | Level 0) - Aug 21, 2024 - Abstract #SSIEM2024SSIEM_1107;
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 T?gal is an effective approach for the treatment of GM1 at a low viral dose.
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma
NEUROCOGNITIVE DEVELOPMENTS IN SIBLINGS WITH NEUROPATHIC MPS-II RECEIVING CONVENTIONAL AND NOVEL ENZYME REPLACEMENT THERAPIES: AN UPDATE (Poster Room | Level 0) - Jul 30, 2024 - Abstract #SSIEM2024SSIEM_488;
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.
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma
GENE THERAPY FOR GM1 GANGLIOSIDOSIS MEDIATED BY AAV VECTOR CARRYING BBB-PENETRABLE ENZYME (Poster Room | Level 0) - Jul 30, 2024 - Abstract #SSIEM2024SSIEM_443;
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 T?gal is an effective approach for the treatment of GM1 at a low viral dose.
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma, Takeda
Preclinical, Journal: Transferrin Receptor-Targeted Iduronate-2-sulfatase Penetrates the Blood-Retinal Barrier and Improves Retinopathy in Mucopolysaccharidosis II Mice. (Pubmed Central) - Oct 20, 2023
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.
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma, Takeda
Trial completion date, Trial primary completion date: An Extension Study of JR-141-BR21 in Patients With Mucopolysaccharidosis II (clinicaltrials.gov) - Jun 23, 2023
P2, N=19, Active, not recruiting,
These data suggest that treatment with pabinafusp alfa may be of therapeutic benefit for MPS II patients with neurological symptoms. Trial completion date: Dec 2026 --> Mar 2024 | Trial primary completion date: Dec 2026 --> Mar 2024
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma, Takeda
Trial completion date, Trial primary completion date: A Phase III Study of JR-141 in Patients With Mucopolysaccharidosis II (STARLIGHT) (clinicaltrials.gov) - Jun 13, 2023
P3, N=80, Recruiting,
Trial completion date: Dec 2026 --> Mar 2024 | Trial primary completion date: Dec 2026 --> Mar 2024 Trial completion date: Oct 2026 --> Jan 2026 | Trial primary completion date: Oct 2026 --> Jan 2026
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma, Takeda
Trial completion date, Trial primary completion date: A Phase III Study of JR-141 in Patients With Mucopolysaccharidosis II (STARLIGHT) (clinicaltrials.gov) - Jun 5, 2023
P3, N=80, Recruiting,
Trial completion date: Oct 2026 --> Jan 2026 | Trial primary completion date: Oct 2026 --> Jan 2026 Trial completion date: Jan 2026 --> Oct 2026 | Trial primary completion date: Jan 2026 --> Oct 2026
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma, Takeda
Innovative Mechanisms of Pre-Market Authorization Access for Rare Diseases in Brazil. a Case Study of Pabinafusp-Alfa for Mucopolysaccharidosis Type II () - Apr 25, 2023 - Abstract #ISPOR2023ISPOR_2969;
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.
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma, Takeda
Gene Therapy for GM1 Gangliosidosis Mediated by AAV Vector Carrying BBB-Penetrable Enzyme (Board No. 1344) - Apr 21, 2023 - Abstract #ASGCT2023ASGCT_1858;
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-?gal downed in half and with high doses of TfR-?gal was found to be at the same level as in wild-type mice.Furthermore, TfR-?gal treated mice exhibited improvements in some of the behavioral experiments such as open field test. These results show that intravenous administration of AAV- TfR-?gal is an effective approach for the treatment of GM1 at such a low viral dose.
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma, Takeda
Trial completion date, Trial primary completion date: A Phase III Study of JR-141 in Patients With Mucopolysaccharidosis II (STARLIGHT) (clinicaltrials.gov) - Jul 7, 2022
P3, N=80, Recruiting,
These long-term results support the clinical development of idursulfase-IT for patients with MPS II with cognitive impairment. Trial completion date: Aug 2024 --> Jan 2026 | Trial primary completion date: Aug 2024 --> Jan 2026
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma, Takeda
Preclinical, Journal: Dose-dependent effects of a brain-penetrating iduronate-2-sulfatase on neurobehavioral impairments in mucopolysaccharidosis II mice. (Pubmed Central) - Jun 8, 2022
We recently showed that pabinafusp alfa, a blood-brain-barrier-penetrating fusion protein consisting of iduronate-2-sulfatase and anti-human transferrin receptor antibody, stabilized learning ability by preventing the deposition of HS in the CNS of MPS II mice...Notably, the water maze test performance was inversely correlated with the HS levels in the brain and CSF. This study provides nonclinical evidence substantiating a quantitative dose-dependent relationship between HS reduction in the CNS and neurological improvements in MPS II.
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma, Takeda
Enrollment change: A Phase III Study of JR-141 in Patients With Mucopolysaccharidosis II (STARLIGHT) (clinicaltrials.gov) - Apr 29, 2022
P3, N=80, Recruiting,
Increased understanding of disease burden and resource use may enable the development of models of healthcare resource utilization in patients with MPS II and contribute to improvements in disease management and patient care. N=50 --> 80
- |||||||||| recombinant-iduronate-2-sulfatase (JR-032) / GSK, JCR Pharma, idursulfase (JR-141) / JCR Pharma
Preclinical, Journal: Clearance of heparan sulfate in the brain prevents neurodegeneration and neurocognitive impairment in MPS II mice. (Pubmed Central) - Dec 16, 2021
Furthermore, HS concentrations in the brain and reduction thereof by pabinafusp alpha correlated with those in the cerebrospinal fluid (CSF). Thus, repeated intravenous administration of pabinafusp alfa to MPS II mice decreased HS deposition in the brain, leading to prevention of neurodegeneration and maintenance of neurocognitive function, which may be predicted from HS concentrations in CSF.
- |||||||||| recombinant-iduronate-2-sulfatase (JR-032) / GSK, JCR Pharma, idursulfase (JR-141) / JCR Pharma
P2/3 data, Journal: A Phase 2/3 Trial of Pabinafusp Alfa, IDS Fused with Anti-Human Transferrin Receptor Antibody, Targeting Neurodegeneration in MPS-II. (Pubmed Central) - Oct 22, 2021
Pabinafusp alfa (JR-141) is a novel enzyme drug that crosses the blood-brain barrier by transcytosis via transferrin receptors...Drug-related adverse events were mild or moderate in severity, transient, and manageable. The results establish delivery across the BBB of pabinafusp alfa as an effective therapeutic for treating both the CNS and peripheral symptoms of patients with MPS-II.
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma, Takeda
Trial primary completion date: An Extension Study of JR-141-BR21 in Patients With Mucopolysaccharidosis II (clinicaltrials.gov) - Sep 17, 2021
P2, N=18, Active, not recruiting,
The results establish delivery across the BBB of pabinafusp alfa as an effective therapeutic for treating both the CNS and peripheral symptoms of patients with MPS-II. Trial primary completion date: May 2021 --> Dec 2026
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma, Takeda
Trial completion date, Trial initiation date, Trial primary completion date: A Phase III Study of JR-141 in Patients With Mucopolysaccharidosis II (STARLIGHT) (clinicaltrials.gov) - Aug 18, 2021
P3, N=50, Not yet recruiting,
Trial primary completion date: May 2021 --> Dec 2026 Trial completion date: Mar 2024 --> Aug 2024 | Initiation date: Mar 2021 --> Aug 2021 | Trial primary completion date: Mar 2024 --> Aug 2024
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma, Takeda
Trial completion, Enrollment change: A Study of JR-141 in Patients With Mucopolysaccharidosis II (clinicaltrials.gov) - Feb 3, 2021
P2/3, N=28, Completed,
Trial completion date: Mar 2024 --> Aug 2024 | Initiation date: Mar 2021 --> Aug 2021 | Trial primary completion date: Mar 2024 --> Aug 2024 Active, not recruiting --> Completed | N=20 --> 28
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma, Takeda
Enrollment closed, Trial completion date: An Extension Study of JR-141-BR21 in Patients With Mucopolysaccharidosis II (clinicaltrials.gov) - Feb 2, 2021
P2, N=18, Active, not recruiting,
Active, not recruiting --> Completed | N=20 --> 28 Enrolling by invitation --> Active, not recruiting | Trial completion date: May 2021 --> Dec 2026
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma, Takeda
Enrollment closed, Trial completion date, Trial primary completion date: An Extension Study of JR-141 in Patients With Mucopolysaccharidosis Type II (clinicaltrials.gov) - Feb 2, 2021
P2/3, N=27, Active, not recruiting,
Enrolling by invitation --> Active, not recruiting | Trial completion date: May 2021 --> Dec 2026 Enrolling by invitation --> Active, not recruiting | Trial completion date: Jun 2021 --> Mar 2030 | Trial primary completion date: Jun 2021 --> Mar 2030
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma, Takeda
Trial completion: A Study of JR-141 in Patients With Mucopolysaccharidosis II (clinicaltrials.gov) - Nov 20, 2019
P2, N=18, Completed,
These results suggest that the drug successfully penetrates the BBB and could have CNS efficacy. Active, not recruiting --> Completed
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma, Takeda
Enrollment closed, Trial completion date, Trial primary completion date: A Study of JR-141 in Patients With Mucopolysaccharidosis II (clinicaltrials.gov) - Mar 1, 2019
P2, N=18, Active, not recruiting,
These results suggest that CSF HS content may be a useful biomarker for evaluating the brain GAG accumulation and the therapeutic efficacy of drugs in patients with MPS II. Recruiting --> Active, not recruiting | Trial completion date: Mar 2019 --> Sep 2019 | Trial primary completion date: Mar 2019 --> Sep 2019
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma, Takeda
Enrollment closed: A Study of JR-141 in Patients With Mucopolysaccharidosis II (clinicaltrials.gov) - Jan 9, 2019
P2/3, N=20, Active, not recruiting,
Recruiting --> Active, not recruiting | Trial completion date: Mar 2019 --> Sep 2019 | Trial primary completion date: Mar 2019 --> Sep 2019 Recruiting --> Active, not recruiting
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma, Takeda
Enrollment open, Trial completion date, Trial initiation date, Trial primary completion date: A Study of JR-141 in Patients With Mucopolysaccharidosis II (clinicaltrials.gov) - Aug 2, 2018
P2, N=18, Recruiting,
Not yet recruiting --> Recruiting Not yet recruiting --> Recruiting | Trial completion date: Dec 2018 --> Mar 2019 | Initiation date: Feb 2018 --> Jul 2018 | Trial primary completion date: Dec 2018 --> Mar 2019
- |||||||||| Izcargo (pabinafusp alfa) / JCR Pharma, Takeda
Trial completion, Trial primary completion date: A Study of JR-141 in Patients With Mucopolysaccharidosis Type II (clinicaltrials.gov) - Oct 12, 2017
P1/2, N=12, Completed,
Not yet recruiting --> Recruiting | Trial completion date: Dec 2018 --> Mar 2019 | Initiation date: Feb 2018 --> Jul 2018 | Trial primary completion date: Dec 2018 --> Mar 2019 Recruiting --> Completed | Trial primary completion date: Sep 2017 --> Mar 2017
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