title: 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.affiliation: Springer, Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand, demail@springer.com.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Lyseng-Williamson
mesh_terms: D002809:Chondroitin Sulfates / Q000037:antagonists & inhibitors / Q000652:urine; D002811:Chondroitinsulfatases / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D056947:Enzyme Replacement Therapy / Q000379:methods*; D006801:Humans; D007632:Keratan Sulfate / Q000037:antagonists & inhibitors / Q000652:urine; D008247:Lysosomes / Q000378:metabolism; D009085:Mucopolysaccharidosis IV / Q000188:drug therapy*
chemical_list: D002809:Chondroitin Sulfates; D007632:Keratan Sulfate; D002811:Chondroitinsulfatases; C102295:GALNS protein, human