Interim Data of Sanflippo B Treatment Presented at WORLDSymposium

BioMarin Pharmaceutical Inc. presented interim data at the 14^th Annual WORLDSymposium in San Diego from a Phase 1/2 trial for BMN 250, an investigational enzyme replacement therapy (ERT) for the treatment of patients with mucopolysaccharidosis IIIB (MPS IIIB; Sanfilippo B syndrome).

BMN 250 is delivered via intracerebrobentricular (ICV) infusion and uses a novel fusion of recombinant human alpha-N-acetylglucosaminidase (NAGLU) with a peptide derived from insulin-like growth factor 2 (IGF2). It is currently being evaluated in a multicenter, international clinical trial assessing safety and tolerability, and it is being developed to restore functional NAGLU activity in the brain.

Sanfilippo B patients are without one of the four enzymes essential for the degradation of heparan sulfate (HS), leading to unhealthy elevations in HS. Cerebrospinal fluid (CSF) HS levels, which were significantly raised at baseline, were quickly reduced to the non-affected or normal range in all patients studied to date, exhibiting the in vivo biochemical activity of the potential therapy.

The study was divided into two parts, and in Part 1 — the completed dose escalation portion of the study – 3 patients received escalating doses (30mg, 100mg, 300mg) of BMN 250 over 9-12 months. This was intended to decipher the safety and pharmacodynamics activity of the drug. Part 2 will roll over patients from an observational study and administer to them the 300mg dose. The interim data cut presented included 3 patients from each portion of the study.

"These studies are generating a robust data set to determine the safety and efficacy of BMN 250 in Sanfilippo B," said Hank Fuchs, M.D., President, Worldwide Research and Development at BioMarin. "While it is still very early, we are encouraged that the interim data is showing normalization of an important biomarker and liver size, as well as suggesting a stabilization in cognitive decline.”

All patients enrolled in the study have enlarged livers as confirmed by abdominal MRI scans, and all patients in Part 1 experienced decreases in liver size into the normal range for age. These data exhibit the ability of ICV-administered BMN 250, when received through the central nervous system (CNS), to reach the peripheral circulation and show activity in somatic organs.

"We are pleased with the preliminary data from the three patients in the dose escalation stage of the study. Our experience in ICV administration of an enzyme replacement therapy combined with more than two decades of experience in developing MPS treatments has allowed us to reach this important step," said Dr Fuchs at the 13th International Congress of Inborn Errors of Metabolism (ICIEM) 2017 in September. "We are grateful to the children and the families who are participating in this early clinical study."

In December 2014, the U.S. Food and Drug Administration granted BMN 250 orphan drug designation and clinical studies were first initiated in mid-2015.

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