Galsulfase (Naglazyme) for the Treatment of Maroteaux-Lamy syndrome (Mucopolysaccharidosis VI; MPS VI)

Mucopolysaccharide storage disorders are caused by the deficiency of specific lysosomal enzymes required for the catabolism of GAG. Mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome) is characterized by the absence or marked reduction in N–acetylgalactosamine 4-sulfatase. The sulfatase activity deficiency results in the accumulation of the GAG substrate, dermatan sulfate, throughout the body. This accumulation leads to widespread cellular, tissue, and organ dysfunction. NAGLAZYME is intended to provide an exogenous enzyme that will be taken up into lysosomes and increase the catabolism of GAG. Galsulfase uptake by cells into lysosomes is most likely mediated by the binding of mannose-6-phosphate-terminated oligosaccharide chains of galsulfase to specific mannose-6-phosphate receptors.


NAGLAZYME (galsulfase) is a normal variant form of the polymorphic human enzyme, N–acetylgalactosamine 4-sulfatase that is produced by recombinant DNA technology in a Chinese hamster ovary cell line. Galsulfase is a glycoprotein with a molecular weight of approximately 56 kD. The recombinant protein is comprised of 495 amino acids and contains six asparagine-linked glycosylation sites, four of which carry a bis mannose-6-phosphate mannose7 oligosaccharide for specific cellular recognition. Post-translational modification of Cys53 produces the catalytic amino acid residue, Cα-formylglycine, which is required for enzyme activity and is conserved in all members of the sulfatase enzyme family.

INDICATIONS AND USAGE
NAGLAZYME is indicated for patients with Mucopolysaccharidosis VI (MPS VI). NAGLAZYME has been shown to improve walking and stair-climbing capacity.

DOSAGE AND ADMINISTRATION
The recommended dosage regimen of NAGLAZYME is 1 mg/kg of body weight administered once weekly as an intravenous infusion

ADVERSE REACTIONS
The most frequent serious adverse events related to the use of NAGLAZYME occurred during infusions and included urticaria of the face and neck, bronchospasm, respiratory distress, and apnea (see WARNINGS: Infusion Reactions). The most common adverse reactions observed in the clinical studies were headache, fever, arthralgia, vomiting, upper respiratory infections, abdominal pain, diarrhea, ear pain, cough, and otitis media. The most common adverse reactions requiring interventions were infusion-related reactions


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