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

Chester B. Whitley, Suresh Vijay, Bert Yao, Mercé Pineda, Geoff J.M. Parker, Sandra Rojas-Caro, Xiaoping Zhang, Yang Dai, Amy Cinar, Gillian Bubb, Kiran C. Patki, Maria L. Escolar

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Mucopolysaccharidosis IIIB is caused by a marked decrease in N-acetyl-α-D-glucosaminidase (NAGLU) enzyme activity, which leads to the accumulation of heparan sulfate in key organs, progressive brain atrophy, and neurocognitive decline. In this open-label study, 11 eligible patients aged 2 to <12 years (developmental age ≥ 1 year) were sequentially allocated to recombinant human NAGLU enzyme (SBC-103) in 3 staggered- and escalating-dose groups (0.3 mg/kg [n = 3], 1.0 mg/kg [n = 4], or 3.0 mg/kg [n = 4]) by intravenous infusion every 2 weeks for 24 weeks, followed by a 4-week interruption (Part A), treatment at 1.0 and/or 3.0 mg/kg every 2 weeks starting at week 28 (Part B), and treatment at 5.0 or 10.0 mg/kg every 2 weeks (Part C) for approximately 2 total years in the study. The primary objective of the study was safety and tolerability evaluation; secondary objectives included evaluation of SBC-103 effects on total heparan sulfate levels in cerebrospinal fluid (CSF), brain structural magnetic resonance imaging (cortical gray matter volume), and neurocognitive status (age equivalent/developmental quotient). During the study, 13 treatment-emergent serious adverse events (SAEs) occurred in 3 patients; 32 infusion-associated reactions (IARs) occurred in 8 patients. Most AEs were mild and intravenous treatment with SBC-103 was well tolerated. Mean (SD) changes from baseline at 52 weeks in Part C for the 5.0 and 10.0 mg/kg doses, respectively, were: −4.7% (8.3) and − 4.7% (14.7) for heparan sulfate levels in CSF, −8.1% (3.5) and − 10.3% (9.4) for cortical gray matter volume, +2.3 (6.9) points and +1.0 (9.2) points in cognitive age equivalent and −8.9 (10.2) points and −14.4 (9.2) points in developmental quotient. 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.

Original languageEnglish (US)
Pages (from-to)131-138
Number of pages8
JournalMolecular Genetics and Metabolism
Volume126
Issue number2
DOIs
StatePublished - Feb 2019

Bibliographical note

Funding Information:
This study was sponsored by Alexion Pharmaceuticals, Inc. Editorial and writing support was provided by Stephanie Leinbach, PhD, and Elizabeth Daro-Kaftan, PhD, of Peloton Advantage, LLC, and funded by Alexion Pharmaceuticals , Inc.

Publisher Copyright:
© 2018 Elsevier Inc.

Keywords

  • Enzyme replacement therapy
  • Heparan sulfate
  • Lysosomal storage disease
  • Mucopolysaccharidosis
  • SBC-103
  • Sanfilippo syndrome

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this