The trial is intended for the treatment of the lysosomal storage disorder mucopolysaccharidosis type IVA (MPS IVA), or Morquio A syndrome. Preliminary clinical data from the first 24 weeks of the study (12 weeks at 0.1mg/kg and 12 weeks at 1.0mg/kg) have been evaluated. BioMarin plans to announce top-line results for the full 36-week study after completion of dosing at 2.0mg/kg in the second quarter of 2010.
Keratan sulfate (KS) levels fall within a few weeks after the start of therapy. Improvements in 6-minute walk distance and 3-minute stair climb at 24 weeks are consistent with those observed with clinical studies for MPS I, MPS II, and MPS VI. The frequency and severity of infusion reactions appear comparable to those observed with Naglazyme and Aldurazyme.
The phase I/II study is designed as an open-label, within-patient dose escalation trial in approximately 20 patients followed by a treatment continuation phase. During the dose escalation phase of the study, subjects receive weekly intravenous infusions of GALNS in three consecutive 12-week dosing intervals: 0.1mg/kg for 12 weeks, 1.0mg/kg for 12 weeks and 2.0mg/kg for 12 weeks. The objectives of the phase I/II study are to evaluate safety, pharmacokinetics, pharmacodynamics, clinical response to therapy and to identify the optimal dose of GALNS for future studies.
Hank Fuchs, chief medical officer of BioMarin, said: "Although still early, we are encouraged by these initial signals of efficacy of GALNS enzyme replacement therapy for Morquio disease. Additional results will become available following the 2.0mg/kg dose phase, but compared to other studies we have conducted in MPS diseases, we feel encouraged by the reduction in KS and improvements in walk distance and stair climb.
"Based on these results, we feel more confident about endurance as a primary endpoint for a Phase III trial and that a Phase III trial can be conducted as expeditiously as previous trials of enzyme replacement therapy. We plan to work closely with the FDA and other health authorities to finalize a Phase III protocol after the completion of the current study and have increased confidence that we will initiate a Phase III registration-enabling program by the fourth quarter of 2010 or the first quarter of 2011."
Jean-Jacques Bienaime, chief executive officer of BioMarin, said: "Based on these data, we are more optimistic about the GALNS program as we continue to move closer to providing a treatment option for Morquio patients. The number of Morquio patients identified already exceeds the number of MPS VI patients on Naglazyme, and an ERT for Morquio will fit perfectly into our global commercial infrastructure without the need for significant additional commercialization costs.
"2010 is shaping up to be an eventful year for BioMarin. In addition to results from the Morquio Phase I/II trial expected in the second quarter, we expect to report Phase II PEG-PAL results in mid-2010 and Phase I BMN 195 results in the third quarter of 2010. We look forward to keeping you updated on the progress of our clinical programs."