title: Reduction of Plasma Globotriaosylsphingosine Levels After Switching from Agalsidase Alfa to Agalsidase Beta as Enzyme Replacement Therapy for Fabry Disease.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors: Lysosomal Disorders Research and Treatment Unit, Center for Clinical Trials, 11212 Waples Mill Road, Fairfax, VA, 22030, USA. ogokeralpan@oandoalpan.com.
authors: Ozlem
authors: O
authors: Goker-Alpan
authors: Emory University School of Medicine, Atlanta, GA, USA.
authors: Michael J
authors: MJ
authors: Gambello
authors: The Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors: Gustavo H B
authors: GH
authors: Maegawa
authors: Infusion Associates, Grand Rapids, MI, USA.
authors: Khan J
authors: KJ
authors: Nedd
authors: Genzyme, A Sanofi Company, Cambridge, MA, USA.
authors: Daniel J
authors: DJ
authors: Gruskin
authors: Genzyme, A Sanofi Company, Cambridge, MA, USA.
authors: Larry
authors: L
authors: Blankstein
authors: University Research Foundation for Lysosomal Storage Diseases, Coral Springs, FL, USA.
authors: Neal J
authors: NJ
authors: Weinreb