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.