Synageva BioPharma Corp, a bio-pharmaceutical company developing therapeutic products for rare disorders, announced dosing with SBC-103 in patients with mucopolysaccharidosis IIIB (MPS IIIB, also known as Sanfilippo B syndrome) has begun as part of a phase 1/2 study. In addition, the US Food and Drug Administration (FDA) recently granted SBC-103 Fast Track designation.  Fast Track is a process designed to facilitate development and expedite review of drugs to treat serious and life-threatening conditions and fill an unmet medical need to get important new drugs to patients expeditiously.

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 (HS) in the brain and other organs.  The accumulation of abnormal HS in multiple cells and tissues 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 designed to replace the missing (or deficient) NAGLU enzyme.

"This is a very exciting time for individuals with MPS IIIB and their families and we are delighted to help support the advancement of this important program," says Christine Lavery, chief executive of the Society for Mucopolysaccharide Diseases (the MPS Society U.K.).  "MPS IIIB is a progressive, life-limiting disease and it is encouraging to see this program progress from preclinical to clinical studies."

Chester B. Whitley, MD, Professor, Advanced Therapies Programme, Department of Paediatrics and Experimental and Clinical Pharmacology at the University of Minnesota, Minneapolis, MN, and investigator in the trial says, "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."

"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," says Sanj K. Patel, president and chief executive officer of Synageva.  "The advancement of this programme 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 trial will enroll approximately nine 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.

SBC-103 has favourable 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.

The company is also conducting natural history studies in MPS IIIB. These include a retrospective natural history study of deceased MPS IIIB patients that began in July 2013 and a prospective, longitudinal natural history study in living MPS IIIB patients that began in September 2014. Natural history studies can help build an understanding of the manifestations and progression of disease and provide insights into biomarkers and other measures that may be useful as clinical outcomes.

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.

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