One month after Biomarin announced
their drug BMN 250 was granted orphan drug designation for treating patients with Sanfilippo syndrome type B [mucopolysaccharidosis (MSBP) IIIB], Synageva has announced
they have begun a Phase I/II study with their compound, SBC-103, in patients with Sanfilippo B.
Sanfilippo B, or MPS IIIB, is a rare disease caused by a decrease in alpha-N-acetyl-glucosaminidase (NAGLU) enzyme activity, which leads to the buildup of abnormal amounts of heparan sulfate in the brain and other organs. The accumulation leads to severe cognitive decline, behavioral problems, speech loss, increasing loss of mobility, and premature death. SBC-103 is a recombinant form of natural human NAGLU (ie, enzyme replacement therapy).
Chester B. Whitley, PhD, MD, Professor, Advanced Therapies Program, Department of Pediatrics and Experimental and Clinical Pharmacology at the University of Minnesota, Minneapolis, MN, and investigator in the trial said:
"Administering the very first dose of this recombinant enzyme is an important milestone for patients afflicted with this otherwise untreatable, lethal disease. This approach challenges the century-long dogma that the blood-brain barrier is impenetrable. The potential impact for these children cannot be overestimated. Sanfilippo syndrome was discovered at the University of Minnesota, and our team is uniquely prepared and excited to help assess treatment for these patients."
Sanj K. Patel, President and Chief Executive Officer of Synageva added:
"The start of dosing in patients with Synageva's second, first-mover program and the first clinical trial of an enzyme replacement therapy for MPS IIIB is an important step forward for this community and the company."
"The advancement of this program to clinical trials was made possible through the dedication and commitment from patients and their families affected by MPS IIIB and the diligent efforts by our research and development team. Lysosomal disease enzyme replacement therapies with the recombinant form of the natural human enzymes are the gold standard of treatment for patients with these devastating diseases, and the results from this clinical trial will help further our understanding of the role of SBC-103 in MPS IIIB."
The Phase I/II trial will enroll approximately 9 patients, two years of age or greater but less than 12 years of age, with definitive diagnosis of MPS IIIB and developmental delay. Patients will be treated in one of three different dosing cohorts (0.3 mg/kg, 1.0 mg/kg or 3.0 mg/kg) with every other week intravenous administrations of SBC-103 for 24 weeks. Patients who meet qualifying criteria may continue therapy with SBC-103 for an extended treatment period that will last up to 128 weeks.
The primary endpoint of the trial is safety and tolerability of intravenous administration of SBC-103 in patients with MPS IIIB. The study will also determine the effects of dosing with SBC-103 on the onset, magnitude, and reversibility of changes in levels of total HS in cerebral spinal fluid (CSF), serum, and urine as well as measure the effects of neurocognitive and developmental function and change in brain structures as assessed by magnetic resonance imaging. Exploratory biomarkers, SBC-103 concentration in CSF, MPS IIIB disease characteristics, symptoms, and quality of life will also be measured. The company plans to report preliminary data from this study during the second half of this year. The company is also conducting natural history studies in MPS IIIB.
SBC-103 was granted orphan designation by the FDA in April 2013 and the European Medicines Agency (EMA) in June 2013 and received Fast Track designation by the FDA in January 2015.
Image of heparin sulfate subunit courtesy wikimedia commons.