PubMed2005
Galsulfase [Aryplase, arylsulfatase B, BM 102, Naglazyme, rhASB, recombinant human N-acetylgalactosamine-4-sulfatase, recombinant human arylsulfatase B] is under development with BioMarin Pharmaceutical as an enzyme replacement therapy for the treatment of mucopolysaccharidosis (MPS) VI. MPS VI (also known as Maroteaux-Lamy syndrome) is a progressive, debilitating genetic disease resulting in early death. Patients with MPS VI have a deficiency in the arylsulfatase B (ASB) enzyme that is essential for the progressive breakdown of certain complex carbohydrates. The deficiency in ASB results in the build-up of carbohydrate residues in the lysosomes in all cells of the body. Patients are usually diagnosed at 6-24 months of age, and the symptoms include deceleration of growth, enlarged liver and spleen, skeletal and joint deformities, and upper airway obstruction. Patients do not survive past 20-30 years of age in the more severe cases, but may live longer with the milder cases, but with significant medical problems. While the symptoms of MPS VI are similar to those of MPS I, mental retardation associated with the severe forms of MPS I had not been reported for patients with MPS VI. For some patients, bone marrow transplantation is a treatment, albeit risky, option. MPS VI afflicts approximately 1100 patients in the world. In November 2004, BioMarin announced that it has filed a Biologics License Application (BLA) with the the US FDA for galsulfase for the treatment of MPS VI. The company has requested a priority review as part of the BLA submission, which, if granted, is expected to be completed within 6 months of submission. The FDA accepted the filing of the BLA for galsulfase for MPS VI in February 2005, and granted it a 6-month priority review period. The FDA's decision is due on 31 May 2005. The FDA has granted galsulfase orphan drug status and fast-track designation. Orphan drug status will provide BioMarin Pharmaceutical with 7 years of marketing exclusivity for galsulfase in the US providing that galsulfase is the first agent to gain approval in the US for MPS VI. BioMarin received an orphan drug designation from the EC for galsulfase for the treatment of MPS VI. Following positive safety and efficacy results from the phase I study with galsulfase, BioMarin Pharmaceutical commenced and successfully completed a phase II trial with rhASB in ten patients with MPS VI. This 24-week, open-label, multicentre trial was conducted at two sites, in the US and Australia (at the Lysosomal Diseases Research Unit, Women's and Children's Hospital, Adelaide, Australia, by Dr John Hopwood), and evaluated the safety, efficacy and pharmacokinetics of weekly intravenous infusions of galsulfase at a dose of 1.0 mg/kg. BioMarin Pharmaceutical completed a phase I/II clinical trial of galsulfase in six patients with MPS VI in the Children's Hospital, Oakland, CA, USA, with Dr Paul Harmatz as a principal investigator. This randomised, double-blind study evaluated the safety and efficacy of two doses of galsulfase administered by weekly intravenous infusions for 24 weeks. Five patients from the phase I study had completed the 24-week, open-label extension study. Data from this study confirmed safety and good tolerability of both doses of galsulfase with the 1.0 mg/kg dose producing greater sustained effects. The patients will continue receiving therapy in the future. Seven preclinical trials with galsulfase were conducted in a naturally occurring feline model of MPS VI disease at the Lysosomal Diseases Research Unit, Women's and Children's Hospital, Adelaide, Australia, by Dr John Hopwood. The company manufactures galsulfase at a GMP facility licensed from the State of California.