SWITCH
SWITCH Between Agalsidase Beta to Agalsidase Alfa| The Efficacy and Safety of Switch Between Agalsidase Beta to Agalsidase Alfa for Enzyme Replacement in Patients With Anderson-Fabry Disease |
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| Estimated enrollment: | 200 |
| Study start date: | November 2010 |
| Study completion date: |
October 2012 (Final data collection date) |
| Purpose 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®. |
| Background 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. Renal function improved continuously, left ventricular mass index increased under therapy with agalsidase beta and decreased stepwise after switch to Agalsidase alfa. A disease specific severity score (MSSI) stayed unchanged with both therapies. 3 out of the 5 patients reported subjective better overall feeling. Infusion reactions have not been observed with both treatments. Single case reports describe therapy switch from Agalsidase beta to Agalsidase alfa due to infusion reactions. All patients tolerated the new drug without any problems, no further adverse events occurred. |
| Study contact Kristin Brüderlein (CRA)  Fon: +49 381 494 47 37 Fax: +49 381 494 47 48 |
| This study is officially registered under NCT01268241 on clinicaltrials.gov providing additional study information. |