Immunogenicity

  • As with all therapeutic proteins, there is potential for immunogenicity
  • The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay
  • Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including:
     
    • Assay methodology
    • Sample handling
    • Timing of sample collection
    • Concomitant medications
    • Underlying disease

For these reasons, comparison of the incidence of antibodies to MEPSEVII with the incidence of antibodies to other products may be misleading.

Immunogenicity data were available from 23 patients

  • 18/23 patients (78%) developed anti-vestronidase alfa-vjbk antibodies (ADA)  

    • 10/18 (55.6%) ADA-positive patients developed neutralizing antibodies (NAb) on at least one occasion

      • There is no correlation between ADA titer and NAb development

  • 6 treatment-naïve patients had pre-existing ADA titers at baseline

    • ADAs were detected in 5/6 patients post-treatment

      • The post-treatment ADA titers were the same as or below the baseline ADA titer values in 2 patients, but 1 of these 2 patients was positive for NAb

      • ADA titer values after treatment increased 64-fold in 2 patients and 364-fold in the third patient    

  • The presence of ADA titer does not appear to affect reduction in the pharmacodynamic marker, urinary glycosaminoglycans (uGAGs), as assessed in clinical trials