Interim Data of Sanflippo B Syndrome Treatment Presented at ICIEM 2017

Mathew Shanley

At the 13th International Congress of Inborn Errors of Metabolism (ICIEM) 2017 today, BioMarin Pharmaceuticals released interim data from the dose escalation arm of a Phase 1/2 trial for BMN 250 to treat Sanfilippo B syndrome, also known as mucopolysaccharidosis IIIB (MPS IIIB).

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

BMN 250, which is delivered via intracerebrobentricular (ICV) infusion, uses a novel fusion of recombinant human alpha-N-acetylglucosaminidase (NAGLU) with a peptide derived from insulin-like growth factor (IGF2). It is currently being evaluated in a multicenter, international clinical trial assessing safety and tolerability, in addition to the cognitive function of patients with Sanfilippo V receiving BMN 250.

The purpose of the therapy is to restore functional NAGLU activity in the brain.

The trial consisted of 2 parts: Part 1 of the study was a completed dose escalation portion, and Part 2 is an ongoing stable dose portion. The former was designed primarily to establish the safety and pharmacodynamics activity of the drug, and featured 3 patients receiving escalated doses (30mg, 100mg, 300mg) over a 9-12-month period. In this arm, it was shown that the drug rapidly reduced cerebrospinal fluid (CSF) heparin sulfate (HD) levels and liver size, both of which were greater than average at the start of the study.

Overall, it was shown that BMN 250 was well-tolerated by patients with Sanfilippo B, and that cognitive development quotient (DQ), a measure of cognitive function normalized to age was improved in 2 of the 3 patients tested, but it should be noted that these are short term results. Further long-term studies are needed to assess cognitive function over time.

"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 Hank Fuchs, M.D., President, Worldwide Research and Development at BioMarin in a press release. "We are grateful to the children and the families who are participating in this early clinical study."

The most common device-related adverse events (AE) in Part 1 of the study included ICV infection before the initial Binfusion, site erythema, CSF pleocytosis and blood clot in CSF, while the most common AEs related to BMN 250 were pyrexia/fever and bradycardia. No serious treatment emergent or device-related AEs have yet been reported in Part 2. Dose-related AEs and serious adverse events (SAEs) have included vomiting, headache, fever, alteration of consciousness and CSF pleocytosis; however, each of these events was self-limited.

All Part 2 patients are currently receiving 300 mg weekly of BMN 250.

The slides being presented at ICIEM can be accessed via BioMarin here.

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