Enzyme replacement therapy for treating mucopolysaccharidosis type IVA (Morquio A syndrome): effect and limitations

Abstract

Introduction: Following a Phase III, randomized, double-blind, placebo (PBO)-controlled, multinational study in subjects with mucopolysaccharidosis IVA (MPS IVA), enzyme replacement therapy (ERT) of elosulfase alfa has been approved in several countries. The study was designed to evaluate safety and efficacy of elosulfase alfa in patients with MPS IVA aged 5 years and older.

Areas covered: Outcomes of clinical trials for MPS IVA have been described. Subjects received either 2.0 mg/kg/week, 2.0 mg/kg/every other week, or PBO, for 24 weeks. The primary endpoint was the change from baseline 6-min walk test (6MWT) distance compared to PBO. The 6MWT results improved in patients receiving 2 mg/kg weekly compared to PBO. The every other week regimen resulted in walk distances comparable to PBO. There was no change from baseline in the 3 Min Stair Climb Test in both treatment groups. Following completion of the initial study, patients, who continued to receive elosulfase alfa 2 mg/kg weekly (QW) for another 48 weeks (for a total of up to 72-week exposure), did not show additional improvement on 6MWT.

Expert opinion: We suggest that ERT is a therapeutic option for MPS IVA, providing a modest effect and the majority of the effects are seen in the soft tissues.

Keywords:

• Chondroitin-6-sulfate
• enzyme replacement therapy
• keratan sulfate
• mucopolysaccharidosis IVA
• skeletal dysplasia

Declaration of interest

This review article was supported by grants from the Austrian MPS Society, The Bennett Foundation, and International Morquio Organization (Carol Ann Foundation). This work was also supported by Japanese MPS Family Society. WG MacKenzie is a clinical consultant for Biomarin, and MB Bober was a Principal Investigator in the Biomarin sponsored MOR-004 and 005 trials and is also a clinical consultant for the company. RW Mason and S Tomatsu were supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of NIH under grant number P20GM103464. S Tomatsu was supported by National Institutes of Health grant R01HD065767. F Kubaski was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico from Brazil (CNPq). The content of the article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other sponsors. Editorial assistance to the manuscript was provided by Michelle Stofa at Nemours/Alfred I. duPont Hospital for Children. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

This box summarizes key points contained in the article.