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Reduction of Plasma Globotriaosylsphingosine Levels After Switching from Agalsidase Alfa to Agalsidase Beta as Enzyme Replacement Therapy for Fabry Disease

  • Ozlem Goker-AlpanEmail author
  • Michael J. Gambello
  • Gustavo H. B. Maegawa
  • Khan J. Nedd
  • Daniel J. Gruskin
  • Larry Blankstein
  • Neal J. Weinreb
Research Report
Part of the JIMD Reports book series (JIMD, volume 25)

Abstract

Introduction: Agalsidase alfa and agalsidase beta, recombinant enzyme preparations for treatment of Fabry disease (FD), have different approved dosing schedules: 0.2 mg/kg and 1.0 mg/kg every other week (EOW), respectively.

Methods: This open-label, multicenter, exploratory phase 4 study evaluated plasma globotriaosylsphingosine (lyso-GL-3) and plasma and urine globotriaosylceramide (GL-3) levels at baseline and 2, 4, and 6 months after the switch from agalsidase alfa (0.2 mg/kg EOW for ≥12 months) to agalsidase beta (1.0 mg/kg EOW) in 15 male patients with FD. Immunoglobulin (Ig)G antidrug antibody titers were assessed, and safety was monitored throughout the study.

Results: Plasma lyso-GL-3 concentrations decreased significantly within 2 months after switch and reductions continued through month 6 (mean absolute changes, −12.8, −16.1, and −16.7 ng/mL at 2, 4, and 6 months, respectively; all P < 0.001). The mean percentage reduction from baseline was 39.5% (P < 0.001) at month 6. For plasma GL-3, the mean absolute change from baseline (−0.9 μg/mL) and percentage reduction (17.9%) at month 6 were both significant (P < 0.05). Urine GL-3 measurements showed intra-patient variability and changes from baseline were not significant. No clinical outcomes were assessed in this 6-month study, and, therefore, no conclusions can be drawn regarding the correlation of observed reductions in glycosphingolipid concentrations with clinically relevant outcomes. There were no differences in IgG antidrug antibody titers between the two enzymes. The switch from agalsidase alfa to agalsidase beta was well tolerated.

Conclusion: Plasma lyso-GL-3 and GL-3 levels reduced after switching from agalsidase alfa to agalsidase beta, indicating that agalsidase beta has a greater pharmacodynamic effect on these markers at the recommended dose. These data further support the use of agalsidase beta 1.0 mg/kg EOW as enzyme replacement therapy in FD.

Keywords

Enzyme Replacement Therapy Fabry Disease Agalsidase Beta Fabry Disease Patient Agalsidase Alfa 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The authors received editorial/writing support in the preparation of this manuscript provided by Alessia Piazza, PhD, of Excerpta Medica, funded by Genzyme. The authors were responsible for all content and editorial decisions and have not received honoraria related to the development of this publication.

The authors would like to acknowledge the staff at the Genzyme Clinical Specialty Laboratory (Framingham, MA, USA) for performing all laboratory assays.

We dedicate this manuscript to the memory of John A. Barranger who acted as the principal study investigator but sadly passed away.

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Ozlem Goker-Alpan
    • 1
    Email author
  • Michael J. Gambello
    • 2
  • Gustavo H. B. Maegawa
    • 3
  • Khan J. Nedd
    • 4
  • Daniel J. Gruskin
    • 5
  • Larry Blankstein
    • 5
  • Neal J. Weinreb
    • 6
  1. 1.Lysosomal Disorders Research and Treatment Unit, Center for Clinical TrialsFairfaxUSA
  2. 2.Emory University School of MedicineAtlantaUSA
  3. 3.The Johns Hopkins School of MedicineBaltimoreUSA
  4. 4.Infusion AssociatesGrand RapidsUSA
  5. 5.Genzyme, A Sanofi CompanyCambridgeUSA
  6. 6.University Research Foundation for Lysosomal Storage DiseasesCoral SpringsUSA

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