Enzyme Replacement Therapy with Elosulfase alfa for Mucopolysaccharidosis IVA (Morquio A Syndrome): Milestones and Challenges

Introduction: Mucopolysaccharidosis IVA (Morquio A syndrome) is an inherited, autosomal recessive disease caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), which results in excessive lysosomal storage of keratan sulfate and chondroitin-6-sulfate in many tissues and organs. This accumulation causes a systemic skeletal dysplasia and leads to multiple clinical manifestations, including impaired endurance and respiratory function. Elosulfase alfa (trade name Vimizim (R)) otherwise known as BMN 110 is an enzyme replacement drug that was developed by BioMarin Pharmaceutical Inc. and approved for use in the United States by the Food and Drug Administration in 2014 for the treatment of Morquio A syndrome. Areas covered: This paper reviews the pre-clinical trials, seven landmark clinical trials to evaluate safety and efficacy of elosulfase alfa in the treatment of Morquio A syndrome, their milestones, challenges, and current accessibility to the treatment. Expert opinion: Genetic heterogeneity and extensive variability in the clinical presentation of Morquio A patients poses an enormous challenge to evaluate the effectiveness of any treatment for this disease. Thus evaluation of the treatment should be performed on an individual basis using a multi-domain analysis. Although the treatment was well tolerated along all clinical trials, all patients developed antibodies against the infused enzyme. Some studies indicated that there was no association between anti-drug antibody or neutralizing antibody positivity, and worsened treatment outcomes. More analyses need to be performed to reach final conclusions on the effect of immune response and elosulfase alfa treatment response. Overall, elosulfase Alfa is an expensive drug and it is hoped that the drug price decreases in the near future to allow for more families struck by the disease to benefit from the treatment.