lesinidase alfa (SBC-103) / AstraZeneca - LARVOL DELTA

Femoral Structure and Biomechanical Characteristics in Sanfilippo Syndrome Type-B Mice. (PubMed, Int J Mol Sci) - "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. 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."

Journal • Preclinical • Gene Therapies • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Safety, pharmacokinetics and CNS distribution of tralesinidase alfa administered via intracerebroventricular infusion to juvenile cynomolgus monkeys. (PubMed, Toxicol Rep) - "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."

Journal • PK/PD data • CNS Disorders • Hunter Syndrome • Lysosomal Storage Diseases • Ophthalmology • Pediatrics • IGF2

A phase 1/2 study on intracerebroventricular tralesinidase alfa in patients with Sanfilippo syndrome type B. (PubMed, J Clin Invest) - P1/2 | "ICV administration of tralesinidase alfa effectively normalized HS and HS-NRE as a prerequisite for clinical efficacy. Peripheral drug exposure data suggests a role for the glymphatic system in altering tralesinidase alfa efficacy."

Journal • P1/2 data • CNS Disorders • Hepatology • Lysosomal Storage Diseases

Tralesinidase alfa enzyme replacement therapy prevents disease manifestations in a canine model of mucopolysaccharidosis type IIIB. (PubMed, J Pharmacol Exp Ther) - "These findings demonstrate the ability of TA to prevent or limit the biochemical, pathological, and cognitive manifestations of canine MPS IIIB disease, thus providing support of its potential long-term tolerability and efficacy in MPS IIIB subjects. Significance Statement This work illustrates the efficacy and tolerability of tralesinidase alfa as a potential therapeutic for MPS IIIB patients by documenting that direct CNS administration to MPS IIIB dogs prevents accumulation of disease-associated GAGs in lysosomes, hepatomegaly, cerebellar atrophy, and cognitive decline."

Journal • Preclinical • Developmental Disorders • Hepatology • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Pediatrics • Rare Diseases • IGF2

Final results of the phase 1/2, open-label clinical study of intravenous recombinant human N-acetyl-α-d-glucosaminidase (SBC-103) in children with mucopolysaccharidosis IIIB. (PubMed, Mol Genet Metab) - "In summary, SBC-103 was generally well tolerated. Changes in heparan sulfate levels in CSF were small and were not maintained from earlier study time points, there was no clear evidence overall of clinically meaningful improvement in neurocognitive function at the higher doses investigated, and no dose-dependent effects were observed."

Clinical • Journal • P1/2 data