Synageva BioPharma Corp., a biopharmaceutical company developing therapeutic products for rare disorders, announced the completion of enrollment in a phase 1/2 trial with SBC-103 in patients with mucopolysaccharidosis IIIB (MPS IIIB, also known as Sanfilippo B syndrome).

The trial reached its targeted enrollment of nine patients, who are two years of age or greater but less than 12 years of age, with a definitive diagnosis of MPS IIIB and developmental delay.  Patients are being 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 dosing with SBC-103 for an extended period.

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 evaluate the effects of dosing with SBC-103 on the change from baseline levels of total heparan sulfate (HS) in urine, serum, and cerebral spinal fluid (CSF), as well as measure the effects on neurocognitive and developmental function and change in brain structures as assessed by magnetic resonance imaging.  

MPS IIIB is a rare, devastating and life threatening disease which typically presents in children during the first few years of life.  Genetic mutations result in decreased activity of the alpha-N-acetyl-glucosaminidase (NAGLU) enzyme, which leads to a buildup of abnormal amounts of HS in the brain and throughout the body.  Over time, this unrelenting systemic accumulation of HS causes progressive and severe cognitive decline, behavioral problems, speech loss, loss of mobility, and premature death.

MPS IIIB patients have significant unmet medical need, as current treatments are palliative for the behavioral problems, sleep disturbances, seizures, and other complications, and do not address the root cause of MPS IIIB and stop disease progression.

SBC-103 is the recombinant form of natural human NAGLU designed to replace the missing (or deficient) NAGLU enzyme.  SBC-103 has favorable properties for enabling cellular uptake and has shown the ability to overcome the challenges previously encountered in producing recombinant human NAGLU. The advancement of SBC-103 towards the clinic was supported by preclinical studies demonstrating that intravenously administered SBC-103 was able to cross the blood-brain barrier and reduce HS storage in the brain in an MPS IIIB animal model.  In addition, SBC-103 demonstrated transport across an in vitro model of the blood-brain barrier and distributed into the CSF in non-human primate studies.

SBC-103 was granted orphan drug designation by the US Food and Drug Administration (FDA) in April 2013 and the European Medicines Agency (EMA) in June 2013 and received Fast Track designation by the FDA in January 2015.