Elosulfase alfa for the treatment of mucopolysacchoridosis IVA

Abstract

Mucopolysacchariodosis IVA is a lysosomal storage disorder characterized by deficiency of the enzyme N-acetylgalactosamine-6-sulfatase leading to accumulation of glycosaminoglycans. Mucopolysacchariodosis IVA affects many organs, especially the skeletal system. The disease is progressive, leads to serious cardiopulmonary problems and is severely debilitating. Enzyme replacement therapy with elosulfase alfa is the only approved treatment for this rare genetic condition. The results from a Phase III clinical trial demonstrated that elosulfase alfa at dose 2.0 mg/kg weekly given intravenously improved the walking distance in 6 min. The results of the 3-min stair climb test and respiratory function test did not show statistically significant improvement over the placebo. However, the composite end point analysis combining changes from baseline in walking distance in 6 min, 3-min stair climb test and respiratory function showed that at dose 2.0 mg/kg weekly, subjects performed better than the placebo, indicating that the effects of treatment are clinically meaningful. Serious side effects are uncommon and infusion-associated reactions are manageable.

Keywords:

• elosulfase alfa
• enzyme replacement therapy
• Morquio A
• mucopolysaccharidosis IVA
• vimizim^®

Financial & competing interests disclosure

P Tanpaiboon has received honoraria and travel support from BioMarin and was an investigator in the mucopolysaccharidosis IVA clinical trials during 2011–2014. The author has 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 apart from those disclosed.

Key issues

• Mucopolysaccharidosis IVA or Morquio A syndrome is a lysosomal storage disorder which involves multiple organ systems, mainly the skeletal system.

• Enzyme replacement therapy is the only specific treatment approved to date.

• Elosulfase alfa was the first approved enzyme replacement therapy for mucopolysaccharidosis IVA.

• Clinical trial demonstrated that elosulfase alfa could improve 6 min walk test in subjects older than 5 years.

• The benefit of treatment on skeletal system is limited and it does not completely stop disease progression.

• Treatment is generally well tolerated.

• Post-marketing data is required to determine long-term efficacy and safety.

• Clinician should discuss with the patients about cost–benefit and patient’s expectation before starting treatment, since the cost per person per year is high and the clinical benefits are uncertain.