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J Med Genet. 2018 May;55(5):351-358. doi: 10.1136/jmedgenet-2017-104863. Epub 2018 Feb 7.

Agalsidase alfa versus agalsidase beta for the treatment of Fabry disease: an international cohort study.

Author information

Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands.
Department of Internal Medicine I, Division of Nephrology and Cardiology, Comprehensive Heart Failure Center (CHFC) and Fabry Center for Interdisciplinary Therapy (FAZIT), University Hospital Wuerzburg, Wuerzburg, Germany.
Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Haematology, Royal Free London NHS Foundation Trust and University College London, London, UK.
Department of Cardiology, St Bartholomew's Hospital, London, UK.
University College London, London, UK.
Department of Medicine, University of Montreal, Montreal, Canada.
Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada.
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Laboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, The Netherlands.
Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.



Two recombinant enzymes (agalsidase alfa 0.2 mg/kg/every other week and agalsidase beta 1.0 mg/kg/every other week) have been registered for the treatment of Fabry disease (FD), at equal high costs. An independent international initiative compared clinical and biochemical outcomes of the two enzymes.


In this multicentre retrospective cohort study, clinical event rate, left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), antibody formation and globotriaosylsphingosine (lysoGb3) levels were compared between patients with FD treated with agalsidase alfa and beta at their registered dose after correction for phenotype and sex.


387 patients (192 women) were included, 248 patients received agalsidase alfa. Mean age at start of enzyme replacement therapy was 46 (±15) years. Propensity score matched analysis revealed a similar event rate for both enzymes (HR 0.96, P=0.87). The decrease in plasma lysoGb3 was more robust following treatment with agalsidase beta, specifically in men with classical FD (β: -18 nmol/L, P<0.001), persisting in the presence of antibodies. The risk to develop antibodies was higher for patients treated with agalsidase beta (OR 2.8, P=0.04). LVMI decreased in a higher proportion following the first year of agalsidase beta treatment (OR 2.27, P=0.03), while eGFR slopes were similar.


Treatment with agalsidase beta at higher dose compared with agalsidase alfa does not result in a difference in clinical events, which occurred especially in those with more advanced disease. A greater biochemical response, also in the presence of antibodies, and better reduction in left ventricular mass was observed with agalsidase beta.


agalsidase alfa; agalsidase beta; enzyme replacement therapy; ert; fabry disease

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Competing interests: CW has received honoraria for lecturing from Sanofi Genzyme (Cambridge, Massachusetts, USA) and a grant to the institution from Sanofi Genzyme and Shire (Dublin, Ireland). SS, DGB, AK, MI and MLW have served on advisory boards, received fees for speaking or travel support and participated in other clinical trials and registries sponsored by Sanofi Genzyme and Shire. MLW has received travel funds, research funds or consultancy fees from Actelion, Alexion, Amicus, Excelsior, GlaxoSmithKline, Protalix and SumitomoPharma. AM has received honoraria for consultancies and educational activities as well as research support from Shire, Sanofi Genzyme, Protalix/Pfizer (New York City, New York, USA) and Amicus. DO has received speakers honoraria from Sanofi Genzyme and travel assistance from Sanofi Genzyme and Shire. PME has received speaker fees from Shire and consultancy and speaker fees from Sanofi Genzyme, Pfizer and Gilead Sciences (Foster City, California, USA). DAH has received honoraria for speaking and participating in advisory boards and support for research from Shire, Sanofi Genzyme, Amicus (Cranbury, New Jersey, USA) and Protalix (Carmiel, Israel). Also, DAH has a consultancy arrangement through UCL Consultants (London, UK) to support, in part, laboratory research. MB and CEMH have received travel support, honoraria for consultancies and educational grants from Sanofi Genzyme, Shire, Protalix, Actelion (Allschwil, Switzerland) and Amicus. All financial arrangements are made with the AMC Medical Research BV in accordance with the Research Code of the Academic Medical Center.

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