Elosulfase Alfa: a review of its use in patients with mucopolysaccharidosis type IVA (Morquio A syndrome).

Abstract

Elosulfase alfa (Vimizim(®)) is a recombinant form of the human lysosomal enzyme N-acetylgalactosamine-6-sulfatase (GALNS) that is lacking in patients with mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome). It is the first, and currently only, disease-specific treatment option for this very rare, progressively degenerative, autosomal-recessive lysosomal storage disorder. Enzyme replacement therapy with elosulfase alfa aims to restore GALNS activity, thereby preventing the accumulation of keratan sulfate (KS) and chondroitin-6-sulfate in lysosomal compartments of cells that results in the clinical manifestations of MPS IVA. In clinical trials in children and adults with MPS IVA, intravenous elosulfase alfa 2 mg/kg/week provided significant and sustained improvements in urinary levels of KS (a pharmacodynamic biomarker for the disease). In the key placebo-controlled, 24-week, phase 3 trial in patients with MPS IVA aged ≥5 years, elosulfase alfa 2 mg/kg/week significantly improved endurance [least squares mean placebo-adjusted change from baseline in 6-min walk test distance 22.5 m (95 % CI 4.0-40.9)]. Infusion-associated reactions, the primary tolerability issue associated with elosulfase alfa, are generally mild to moderate in severity, self-limiting, and manageable. In the absence of a cure, GALNS enzyme replacement therapy with elosulfase alfa is an important achievement in the treatment of MPS IVA.

• Authors: Katherine A Lyseng-Williamson
• Journal: BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy (BioDrugs) Vol. 28 Issue 5 Pg. 465-75 (Oct 2014) ISSN: 1179-190X [Electronic] New Zealand
• PMID: 25200032 (Publication Type: Journal Article, Review)

Chemical References

• Chondroitin Sulfates
• Keratan Sulfate
• Chondroitinsulfatases
• GALNS protein, human

Topics

• Chondroitin Sulfates (antagonists & inhibitors, urine)
• Chondroitinsulfatases (administration & dosage, adverse effects, therapeutic use)
• Clinical Trials as Topic
• Dose-Response Relationship, Drug
• Enzyme Replacement Therapy (methods)
• Humans
• Keratan Sulfate (antagonists & inhibitors, urine)
• Lysosomes (metabolism)
• Mucopolysaccharidosis IV (drug therapy)