Anderson-Fabry Disease, Fabry Disease, Fabry´s Disease
Conditions
Keywords
Fabry Disease, Fabry´s Disease, Anderson-Fabry Disease
Brief summary
The current approved treatment for Fabry disease is enzyme replacement therapy (ERT). There are actually 2 products in this therapeutic class available: Replagal® (agalsidase alfa) and Fabrazyme® (agalsidase beta). Both are indicated for long-term treatment in patients with a confirmed diagnosis of Fabry disease (alfa-galactosidase A deficiency). Both have been commercially available in Europe for almost 10 years, yet little information is available about the clinical and safety profile of patients who switch from one therapy to the other. An extended shortage of Fabrazyme® that began in June 2009 has necessitated that a large number of patients switch from Fabrazyme® to Replagal®. This offers the possibility to study the clinical status and adverse events in patients who switch from Fabrazyme® to Replagal® on a large-scale basis. In addition, as a result of the increasing Fabrazyme® shortage, many of these patients received a reduced dosage of Fabrazyme® for an extended period before transitioning to treatment with Replagal®.
Detailed description
Aim: Anderson-Fabry disease is an X-linked lysosomal storage disorder resulting from deficiency of the hydrolytic enzyme alfa galactosidase A. Trials of specific therapy by replacement of alfa galactosidase A were commenced in 1999 and subsequently two preparations of alfa galactosidase A received marketing approval by the EMEA in 2001. Clinical trials, observational studies and registry data have provided evidence for efficacy of enzyme replacement therapy (ERT) with alfa galactosidase A in improving symptoms of pain, gastrointestinal disturbance, hypohidrosis, left ventricular mass index, glomerular filtration rate and quality of life in men. There is currently no long-term data showing the impact of enzyme replacement therapy on overall survival. It has been suggested that earlier therapy, before the onset of end organ manifestations, would be more likely to prevent further damage and therefore have the biggest effect on overall survival. There is as yet little evidence to substantiate this hypothesis however clinical trials have recently demonstrated safety and therapeutic effects of enzyme replacement in children. So far, there are only limited data available on the clinical course of the disease and adverse events in patients, switching from one therapeutic alternative to the other. West and Lemoine (16) report clinical effects of a switch from Agalsidase beta to agalsidase alfa in 5 patients with Fabry disease due to shortage of agalsidase beta. The patients were treated with Replagal® for 44 weeks at an average.
Interventions
None listed
Sponsors
CENTOGENE GmbH Rostock
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Hemizygous male or heterozygous female patients at 18 years with genetically confirmed diagnosis of Anderson-Fabry disease. * Written informed consent * Patient had received Fabrazyme® for at least 12 months prior to starting treatment with Replagal® in full dose (i.e. 1.0 mg/kg eow) or any reduced dose prescribed by the treating physician due to the shortage of the medication * Patient has received or is receiving treatment commercially available Replagal® (0.2 mg/kg eow) for intravenous (IV) infusion prescribed by their treatment physician and administered in accordance with the Replagal® prescribing information. * The switch of the medication from Fabrazyme® to Replagal® had to be taken place from September 2009 onwards at the earliest * Patient data includes disease history, measures of Fabry related disease and safety measures
Exclusion criteria
* Concomitant use of Fabrazyme® * Any switch of medication from Fabrazyme® to Replagal® before September 2009 * Any switch from Fabrazyme® to Replagal® for other reasons than Fabrazyme® shortage * Patient has received treatment with any investigational drug or device within the 30 days prior to study entry * No written informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy and Safety of Switch Between Agalsidase Beta to Agalsidase Alfa for Enzyme Replacement in Patients With Anderson-Fabry Disease | 24 month |
Countries
Argentina, Belgium, Croatia, Czechia, Denmark, France, Germany, United Kingdom
Outcome results
None listed