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Elosulfase Alfa: A Review of Its Use in Patients with Mucopolysaccharidosis Type IVA (Morquio A Syndrome)

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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.

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Disclosure

The preparation of this review was not supported by any external funding. K.A. Lyseng-Williamson is a salaried employee of Adis/Springer. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author(s) on the basis of scientific and editorial merit.

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  1. Springer, Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand

    Katherine A. Lyseng-Williamson

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  1. Katherine A. Lyseng-Williamson
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Correspondence to Katherine A. Lyseng-Williamson.

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The manuscript was reviewed by: M. Beck, Children’s Hospital, University of Mainz, Mainz, Germany; D. Hughes, Royal and Free University College Medical School, London, UK; E. Mengel, Villa Metabolica, Centre for Pediatric and Adolescent Medicine, Medical Center University of Mainz, Mainz, Germany; J. Mitchell, Department of Medical Genetics, McGill University Health Centre, Montreal, Quebec, Canada.

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Lyseng-Williamson, K.A. Elosulfase Alfa: A Review of Its Use in Patients with Mucopolysaccharidosis Type IVA (Morquio A Syndrome). BioDrugs 28, 465–475 (2014). https://doi.org/10.1007/s40259-014-0108-z

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