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Table 5 Comparison of safety and efficacy outcomes of the enzyme replacement therapies

From: Fabry disease

  Fabrazyme®, agalsidase beta -
1 mg/kg/14 days
Replagal®, agalsidase alfa -
0.2 mg/kg/14 days
Efficacy data on renal histology At 6 months (n = 58):
- Total clearance of Gb3 in renal intersticial capillary endothelial cells [323]
- Total clearance of Gb3 in glomerular, mesangial and interstitial cells [323]
- Partial clearance of Gb3 in arterial smooth muscular cells [357]
At 54 months:
- Significant clearance maintained in several renal cells types (n = 8) [309]
At 6 months (n = 26), glomeruli with mesangial widening decreased by a mean of 12.5% for patients receiving agalsidase alfa versus a 16.5%
increase for placebo (p = 0.01) [324]
Efficacy data on renal function Significant risk reduction (-61%) of renal, cardiac, cerebrovascular complications and death in per protocol analysis that adjusted on an imbalance in baseline proteinuria (n = 74; p = 0.034) [325]
At 54 months (n = 44) [309]: Stabilization of eGFR for 90% of patients (- 0,4 ml/min/1,73 m2/year) (n = 42)
At 6 months (n = 26) [324]:
- Significant increase of creatinine clearance in treated group versus placebo
- No significant difference of inuline clearance between the 2 groups
At 54 months (n = 25) [327]:
- Patients with stage 1 CKD: average eGFR loss of - 1,6 ml/min/1,73 m2/year
- Patients with stage 2 CKD: average eGFR loss of - 2,6 ml/min/1,73 m2/year
- Patients with stage 3 CKD: average eGFR loss of - 4,9 ml/min/1,73 m2/year [327]
At 5 years (FOS® data):
- Male patients with stage 1 CKD: mean yearly fall in eGFR = -2.83 ml/min/1,73 m2/year
- Male patients with stage 2 CKD: mean yearly fall in eGFR = -2.17 ml/min/1,73 m2/year
- Male patients with stage 3 CKD: mean yearly fall in eGFR = -3.0 ml/min/1,73 m2/year [333]
Efficacy data on cardiac histology Significant Gb3 clearance in cardiac endothelial cells at 6 months [323] maintained at 54 months [309, 359]
No clearance of Gb3 in cardiomyocytes [359]
A mean 20% reduction in myocardial Gb3 content was demonstrated over the 6 months of ERT compared to a mean 10% increase in patients receiving placebo (p = 0.42) [326]
Efficacy data on cardiac function and geometry (clinical trials) Significant risk reduction (-61%) of renal, cardiac, cerebrovascular complications and death in the per protocol analysis that adjusted on an imbalance in baseline proteinuria (n = 74; p = 0.034) [325] Left ventricular mass, as measured by MRI, was significantly reduced following 6 months of treatment with agalsidase alfa compared with placebo (p = 0.041) [326]
Efficacy data on peripheral nervous system based on clinical trials Significant improvement in pain scores at 54 months (p = 0.016) [309]
Significant improvement in quality of life at 54 months (p = 0,007) (n = 52) [309]
Significant decrease of average pain scores at 6 months (n = 26) [324]
Efficacy data on pediatric population based on clinical trials At 12 months (n = 16):
- Significant clearance of plasma Gb3 (normalization)
- Significant clearance of Gb3 in skin specimens
- Patient diaries documented significant reductions
in school absences due to sickness.
- Reduction in gastro-intestinal symptoms [362]
Enzyme replacement with agalsidase alfa was safe. The exploratory efficacy analysis documented increased clearance of Gb3, reductions in neuropathic pain and in the use of pain medication, and improvement of autonomic function (n = 24) [342, 346]
Immunogenicity IgG reported for 90% of patients [323]
IgE reported in a few patients [295, 376]
IgG reported for 56% of the patients
No report of IgE
Infusion time 90 (once safety established) - 180 minutes 40 - 60 minutes
Home based treatment availability after hospital initiation Yes Yes
Treatment costs (in France) - Vial cost (35 mg): 3,370 euros
- Annual cost of therapy for a 70 kg adult patient: 161,781 € (year 2010)
- Vial cost (3.5 mg): 1,685 euros
- Annual cost of therapy for a 70 kg adult patient: 161,781 € (year 2010)
Market authorization approval - European market authorization approval: August 2001
- European Medicines Agency (EMA) exceptional circumstances lifted (February 2008)
- American market authorization approval: April 2003
- European market authorization approval: August 2001
- European Medicines Agency (EMA) exceptional circumstances maintained
- American market authorization approval: none
  1. Note: the comparison has been limited to randomized placebo-controlled clinical trials, their extension studies, and paediatric trials.