Immunogenicity of Elosulfase Alfa, an Enzyme Replacement Therapy in Patients With Morquio A Syndrome: Results From MOR-004, a Phase III Trial

Clin Ther. 2015 May 1;37(5):1012-1021.e6. doi: 10.1016/j.clinthera.2014.11.005. Epub 2014 Dec 6.


Purpose: Morquio A syndrome (mucopolysaccharidosis IVA [MPS IVA]) is a lysosomal storage disorder caused by deficiency of the enzyme N-acetylgalactosamine-6-sulfatase, which is required to degrade the glycosaminoglycan keratan sulfate. Morquio A is associated with extensive morbidity and early mortality. Elosulfase alfa is an enzyme replacement therapy that provides a treatment option for patients with Morquio A. We examined the immunogenicity profile of elosulfase alfa, assessing any correlations between antidrug antibodies and the efficacy and safety outcomes in 176 patients with Morquio A from a 24-week international Phase III trial.

Methods: Patients were randomized to placebo (n = 59) or elosulfase alfa 2.0 mg/kg administered weekly (n = 58) or every other week (n = 59) as an ~4-hour infusion. Blood samples were routinely tested to determine drug-specific total antibody titer and neutralizing antibody (NAb) positivity. Drug-specific immunoglobulin E positivity was tested routinely and in response to severe hypersensitivity adverse events (AEs). Antidrug antibody positivity and titer were compared with efficacy and safety metrics to assess possible correlations.

Findings: The 176 patients in the trial were 54% female, with a mean age of 11.9 years. In all patients treated with elosulfase alfa antidrug antibodies developed, and in the majority, antibodies capable of interfering with cation-independent mannose-6-phosphate receptor binding in vitro (NAb) developed. Less than 10% of patients tested positive for drug-specific IgE during the study. Despite the high incidence of anti-elosulfase alfa antibodies, no correlations were detected between higher total antibody titers or NAb positivity and worsened 6-minute walk test results, urine keratin sulfate levels, or hypersensitivity AEs. Drug-specific IgE positivity had no apparent association with the occurrence of anaphylaxis, other hypersensitivity AEs, and/or treatment withdrawal.

Implications: Despite the universal development of antidrug antibodies, elosulfase alfa treatment was both safe and well tolerated and immunogenicity was not associated with reduced treatment effect. identifier: NCT01275066. (Clin Ther.

Keywords: Morquio A; antibody; efficacy; enzyme replacement therapy; immunogenicity; mucopolysaccharidosis IVA.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / blood
  • Child
  • Child, Preschool
  • Chondroitinsulfatases / administration & dosage
  • Chondroitinsulfatases / adverse effects
  • Chondroitinsulfatases / immunology*
  • Chondroitinsulfatases / therapeutic use
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Hypersensitivity / etiology
  • Drug Hypersensitivity / immunology
  • Enzyme Replacement Therapy / adverse effects
  • Enzyme Replacement Therapy / methods*
  • Female
  • Humans
  • Immunoglobulin E / blood
  • Keratan Sulfate / urine
  • Male
  • Middle Aged
  • Mucopolysaccharidosis IV / drug therapy*
  • Mucopolysaccharidosis IV / immunology
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / immunology
  • Recombinant Proteins / therapeutic use


  • Antibodies, Neutralizing
  • Recombinant Proteins
  • Immunoglobulin E
  • Keratan Sulfate
  • Chondroitinsulfatases
  • GALNS protein, human

Associated data