Delving into the Latest Updates on Tralesinidase alfa with Synapse

Overview

Basic Info

Drug Type

Fusion protein

Synonyms

NAGLU-IGF2 fusion protein

+ [1]

Target

HS

Mechanism

Heparan sulfate sulfatase replacements

Therapeutic Areas

Congenital DisordersEndocrinology and Metabolic DiseaseSkin and Musculoskeletal Diseases+ [1]

Active Indication

Mucopolysaccharidosis IIIMucopolysaccharidoses

Inactive Indication-

Originator Organization

BioMarin Pharmaceutical, Inc.

Active Organization

Allievex Corp.

Inactive Organization

BioMarin Pharmaceutical, Inc.

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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Gene Sequence

Sequence Code 318417585

Source: *****

This is a Phase 3B/4, multicenter, multinational, open label study to further evaluate intracerebroventricular (ICV) delivered AX 250 treatment in MPS IIIB subjects that complete Study 250-202 for up to an additional 3 years (144 weeks) of treatment with AX 250 administered by ICV infusion every other week. Subjects will be evaluated for neurocognitive function, communication, adaptive behavior, quality of life, imaging characteristics and biochemical markers of disease burden. Safety will be assessed by adverse events, clinical labs, and physical exams.

Start Date02 Dec 2022

Sponsor / Collaborator

Allievex Corp.

EUCTR2017-003083-13-GB / Unknown statusPhase 2

A Multicenter, Multinational, Extension Study to Evaluate the Long-Term Safety and Efficacy of Intracerebroventricular AX 250 in Patients with Mucopolysaccharidosis Type IIIB (MPS IIIB, Sanfilippo Syndrome Type B)

Start Date02 Mar 2018

Sponsor / Collaborator

Allievex Corp.

NCT03784287 / Active, not recruitingPhase 2

A Multicenter, Multinational, Extension Study to Evaluate the Long Term Safety and Efficacy of Intracerebroventricular AX 250 in Patients With Mucopolysaccharidosis Type IIIB (MPS IIIB, Sanfilippo Syndrome Type B)

The primary objectives of this study are to evaluate the long-term safety and tolerability of AX 250 administered to subjects with MPS IIIB by an implanted ICV reservoir and catheter and to evaluate the impact of long-term AX 250 treatment on cognitive function in patients with MPS IIIB as assessed by developmental quotient (DQ).

Start Date19 Feb 2018

Sponsor / Collaborator

Allievex Corp.

100 Clinical Results associated with Tralesinidase alfa

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100 Translational Medicine associated with Tralesinidase alfa

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100 Patents (Medical) associated with Tralesinidase alfa

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9

Literatures (Medical) associated with Tralesinidase alfa

12 Sep 2023·International journal of molecular sciences

Femoral Structure and Biomechanical Characteristics in Sanfilippo Syndrome Type-B Mice.

Article

Author: Aguirre, Jose I ; Sommerville, John D ; Chen, Cong ; Ashby, Frederick James ; Jamieson, Julia C ; Andraka, Natalia K ; Castillo, Evelyn J ; Heldermon, Coy D ; Kabbej, Nadia ; Ludwig, Yan

Sanfilippo syndrome Type-B, also known as mucopolysaccharidosis IIIB (MPS IIIB), accounts for approximately one-third of all Sanfilippo syndrome patients and is characterized by a similar natural history as Type-A. Patients suffer from developmental regression, bone malformation, organomegaly, GI distress, and profound neurological deficits. Despite human trials of enzyme replacement therapy (ERT) (SBC-103, AX250) in MPS IIIB, there is currently no FDA approved treatment and a few palliative options. The major concerns of ERT and gene therapy for the treatment of bone malformation are the inadequate biodistribution of the missing enzyme, N-acetyl-α-glucosaminidase (NAGLU), and that the skeleton is a poorly hit target tissue in ERT and gene therapy. Each of the four known human types of MPS III (A, B, C, and D) is usually regarded as having mild bone manifestations, yet it remains poorly characterized. This study aimed to determine bone mineral content (BMC), volumetric bone mineral density (vBMD), and biomechanical properties in femurs MPS IIIB C57BL/6 mice compared to phenotypic control C57BL/6 mice. Significant differences were observed in MPS IIIB mice within various cortical and cancellous bone parameters for both males and females (p < 0.05). Here, we establish some osteogenic manifestations of MPS IIIB within the mouse model by radiographic and biomechanical tests, which are also differentially affected by age and sex. This suggests that some skeletal features of the MPS IIIB mouse model may be used as biomarkers of peripheral disease correction for preclinical treatment of MPS IIIB.

17 Jan 2023·Journal of Clinical Investigation

A phase I/II study on intracerebroventricular tralesinidase alfa in patients with Sanfilippo syndrome type B

Article

Author: von Cossel, Katharina ; Harmatz, Paul ; Batzios, Spyros ; Couce, Maria Luz ; de Castro Lopez, Maria J ; Kovalchin, Joseph ; Cleary, Maureen ; Solano, Martha ; Maricich, Stephen M ; Zanelli, Eric ; Lin, Shuan-Pei ; Kuca, Bernice ; Koehn, Anja ; Shaywitz, Adam J ; Okur, Ilyas ; Kaufman, Brian ; Nestrasil, Igor ; Ezgu, Fatih ; Muschol, Nicole

BackgroundSanfilippo type B is a mucopolysaccharidosis (MPS) with a major neuronopathic component characterized by heparan sulfate (HS) accumulation due to mutations in the NAGLU gene encoding alfa-N-acetyl-glucosaminidase. Enzyme replacement therapy for neuronopathic MPS requires efficient enzyme delivery throughout the brain in order to normalize HS levels, prevent brain atrophy, and potentially delay cognitive decline.MethodsIn this phase I/II open-label study, patients with MPS type IIIB (n = 22) were treated with tralesinidase alfa administered i.c.v. The patients were monitored for drug exposure; total HS and HS nonreducing end (HS-NRE) levels in both cerebrospinal fluid (CSF) and plasma; anti-drug antibody response; brain, spleen, and liver volumes as measured by MRI; and cognitive development as measured by age-equivalent (AEq) scores.ResultsIn the Part 1 dose escalation (30, 100, and 300 mg) phase, a 300 mg dose of tralesinidase alfa was necessary to achieve normalization of HS and HS-NRE levels in the CSF and plasma. In Part 2, 300 mg tralesinidase alfa sustained HS and HS-NRE normalization in the CSF and stabilized cortical gray matter volume (CGMV) over 48 weeks of treatment. Resolution of hepatomegaly and a reduction in spleen volume were observed in most patients. Significant correlations were also established between the change in cognitive AEq score and plasma drug exposure, plasma HS-NRE levels, and CGMV.ConclusionAdministration of tralesinidase alfa i.c.v. effectively normalized HS and HS-NRE levels as a prerequisite for clinical efficacy. Peripheral drug exposure data suggest a role for the glymphatic system in altering tralesinidase alfa efficacy.Trial registrationClinicaltrials.gov NCT02754076.FUNDINGBioMarin Pharmaceutical Inc. and Allievex Corporation.

01 Jan 2023·Toxicology Reports

Safety, pharmacokinetics and CNS distribution of tralesinidase alfa administered via intracerebroventricular infusion to juvenile cynomolgus monkeys

Article

Author: Chandra, Sundeep ; Grover, Anita ; Trombley, Jami L ; Henshaw, Joshua ; Boyd, Robert B ; Nguyen, Annalisa ; Pinkstaff, Jason ; Kovalchin, Joseph ; Wait, Jill Cm ; Melton, Andrew C ; Butt, Mark T ; Reed, Randall P ; Cherukuri, Anu ; McCullagh, Emma ; O'Neill, Charles A ; Adams, Eric L ; Zanelli, Eric

Mucopolysaccharidosis Type IIIB (MPS IIIB) is an ultrarare, fatal pediatric disease with no approved therapy. It is caused by mutations in the gene encoding for lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU). Tralesinidase alfa (TA) is a fusion protein comprised of recombinant NAGLU and a modified human insulin-like growth factor 2 that is being developed as an enzyme replacement therapy for MPS IIIB. Since MPS IIIB is a pediatric disease the safety/toxicity, pharmacokinetics and biodistribution of TA were evaluated in juvenile non-human primates that were administered up to 5 weekly intracerebroventricular (ICV) or single intravenous (IV) infusions of TA. TA administered by ICV slow-, ICV isovolumetric bolus- or IV-infusion was well-tolerated, and no effects were observed on clinical observations, electrocardiographic or ophthalmologic parameters, or respiratory rates. The drug-related changes observed were limited to increased cell infiltrates in the CSF and along the ICV catheter track after ICV administration. These findings were not associated with functional changes and are associated with the use of ICV catheters. The CSF PK profiles were consistent across all conditions tested and TA distributed widely in the CNS after ICV administration. Anti-drug antibodies were observed but did not appear to significantly affect the exposure to TA. Correlations between TA concentrations in plasma and brain regions in direct contact with the cisterna magna suggest glymphatic drainage may be responsible for clearance of TA from the CNS. The data support the administration of TA by isovolumetric bolus ICV infusion to pediatric patients with MPS IIIB.

100 Deals associated with Tralesinidase alfa

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Mucopolysaccharidosis III	Phase 3	US	Allievex Corp.	18 Oct 2022
Mucopolysaccharidosis III	Phase 3	TR	Allievex Corp.	18 Oct 2022
Mucopolysaccharidosis III	Phase 3	CO	Allievex Corp.	18 Oct 2022
Mucopolysaccharidosis III	Phase 3	GB	Allievex Corp.	18 Oct 2022
Mucopolysaccharidosis III	Phase 3	DE	Allievex Corp.	18 Oct 2022
Mucopolysaccharidoses	Phase 2	ES	Allievex Corp.	19 Feb 2018
Mucopolysaccharidoses	Phase 2	TW	Allievex Corp.	19 Feb 2018

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02754076 (Pubmed) Manual	Phase 1/2	Mucopolysaccharidosis III	22	Tralesinidase alfa	(rgzrseyryi) = Resolution of hepatomegaly and a reduction in spleen volume were observed in most patients. jomkiarwix (lhvyflxxlz ) View more	Positive	22 Nov 2022