Safety and Efficacy of Enzyme Replacement Therapy with Agalsidase Beta: An International, Open-label Study in Pediatric Patients with Fabry Disease

Wraith, J. Edmond; Tylki-Szymanska, Anna; Guffon, Nathalie; Lien, Y. Howard; Tsimaratos, Michel; Vellodi, Ashok; Germain, Dominique P.

doi:10.1016/j.jpeds.2007.09.007

« Previous Next »The Journal of Pediatrics
Volume 152, Issue 4 , Pages 563-570.e1, April 2008

Safety and Efficacy of Enzyme Replacement Therapy with Agalsidase Beta: An International, Open-label Study in Pediatric Patients with Fabry Disease

J. Edmond Wraith, MB, ChB
- Royal Manchester Children’s Hospital, Manchester, United Kingdom
- J. Edmond Wraith and Anna Tylki-Szymanska were equal contributors to this article.
Anna Tylki-Szymanska, MD, PhD
- The Children’s Memorial Health Institute, Warsaw, Poland
- Reprint requests: A.Tylki-Szymanska, The Children’s Memorial Health Institute, Warsaw, Poland.
- J. Edmond Wraith and Anna Tylki-Szymanska were equal contributors to this article.
Nathalie Guffon, MD, PhD
- Hôpital Edouard Herriot, Lyon, France
Y. Howard Lien, MD, PhD
- University of Arizona, Tucson, Arizona
Michel Tsimaratos, MD, PhD
- Assistance Publique-Hôpitaux de Marseille la Timone-Enfants, Marseille, France
Ashok Vellodi, MBBS
- Great Ormond Street Hospital for Children, London, United Kingdom
Dominique P. Germain, MD, PhD
- University of Versailles-St Quentin en Yvelines and Centre de référence de la maladie de Fabry et des maladies héréditaires du tissu conjonctif, Assistance Publique-Hôpitaux de Paris, Paris, France

Received 28 December 2006; received in revised form 19 July 2007; accepted 5 September 2007. published online 03 December 2007.

Objective

To evaluate the safety and explore the efficacy of enzyme replacement therapy with agalsidase beta (recombinant human α-galactosidase A; Fabrazyme [Genzyme Corporation, Cambridge, MA]) in pediatric patients with Fabry disease, a genetic disorder in which deficient endogenous enzyme causes pathogenic tissue accumulation of globotriaosylceramide (GL-3).

Study design

Fourteen male and 2 female patients, 8 to 16 years old, were treated in this open-label study. A 12-week observation period to collect baseline data preceded the 48-week treatment period when agalsidase beta (1 mg/kg) was infused intravenously every 2 weeks. No primary efficacy end point was specified.

Results

Before treatment, results of skin biopsies from 12 male patients showed moderate or severe GL-3 accumulation in superficial dermal capillary endothelial cells; with treatment, these cells were completely cleared of GL-3 in week-24 biopsies from all 12 male patients and in all available week-48 biopsies. With treatment, reports of gastrointestinal symptoms declined steadily. Patient diaries documented significant reductions in school absences due to sickness. Agalsidase beta was generally well tolerated; most treatment-related adverse events were mild or moderate infusion-associated reactions involving rigors, fever, or rhinitis.

Conclusions

Agalsidase beta safely and effectively reduced the GL-3 accumulation in dermal endothelium already evident in children with Fabry disease. Early intervention may prevent irreversible end-organ damage from chronic GL-3 deposition.

Abbreviations: AE, Adverse event, αGal, α-Galactosidase A, BMI, Body mass index, ECG, Electrocardiography, electrocardiogram, ELISA, Enzyme-linked immunoadsorbent assay, ERT, Enzyme replacement therapy, IAR, Infusion-associated reaction, IV, Intravenous, GFR, Glomerular filtration rate, GL-3, Globotriaosylceramide, IgE, Immunoglobulin E, IgG, Immunoglobulin G, OMIM, Online Mendelian Inheritance in Man, r-hαGal, Recombinant human α-Galactosidase A, SAE, Serious adverse event