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Journal of Inherited Metabolic Disease

, Volume 28, Issue 4, pp 575–583 | Cite as

Enzyme replacement therapy in Japanese Fabry disease patients: The results of a phase 2 bridging study

  • Y. Eto
  • T. Ohashi
  • Y. Utsunomiya
  • M. Fujiwara
  • A. Mizuno
  • K. Inui
  • N. Sakai
  • T. Kitagawa
  • Y. Suzuki
  • S. Mochizuki
  • M. Kawakami
  • T. Hosoya
  • M. Owada
  • H. Sakuraba
  • H. Saito
Article

Summary

Fabry Disease (α-galactosidase A deficiency) is an X-linked hereditary disorder leading to the pathological accumulation of globotriaosylceramide (GL-3) in lysosomes, particularly in the vascular endothelium of the kidney, heart and brain. We report the results of an open-label phase 2 study that was undertaken to evaluate whether ethnic differences exist that would affect agalsidase beta (Fabrazyme) treatment of Fabry patients in the Japanese population, relative to safety and efficacy. The study design mirrored the design of the completed phase 3 clinical trial that led to approval of the product agalsidase beta. The 13 Japanese, male Fabry patients enrolled in the study received the enzyme replacement therapy over a period of 20 weeks as biweekly infusions. All selected efficacy end points showed improvements that were comparable with findings from the phase 3 study. These improvements included reductions of GL-3 accumulation in both kidney and skin capillary endothelial cells to (near) normal levels (92% of patients). Kidney and plasma GL-3 levels decreased by 51.9% and 100%, respectively, by ELISA. Renal function remained normal. Fabry-associated pain, and quality of life, showed improvement over baseline in multiple categories. Related adverse events were mild or moderate in intensity and mostly infusion-associated (fever and rigors). As expected, IgG antibody formation was observed in 85% of the patients, but had no effect on treatment response. These results suggest that treatment with agalsidase beta is safe and effective in Japanese patients with Fabry disease. With regard to safety and efficacy, no differences were observed as compared to the caucasian population.

Keywords

Vascular Endothelium Enzyme Replacement Therapy Caucasian Population Fabry Disease Capillary Endothelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© SSIEM and Springer 2005

Authors and Affiliations

  • Y. Eto
    • 1
    • 8
  • T. Ohashi
    • 1
  • Y. Utsunomiya
    • 1
  • M. Fujiwara
    • 1
  • A. Mizuno
    • 2
  • K. Inui
    • 3
  • N. Sakai
    • 3
  • T. Kitagawa
    • 4
  • Y. Suzuki
    • 5
  • S. Mochizuki
    • 1
  • M. Kawakami
    • 1
  • T. Hosoya
    • 1
  • M. Owada
    • 4
  • H. Sakuraba
    • 6
  • H. Saito
    • 7
  1. 1.Tokyo Jikei University School of MedicineTokyo
  2. 2.Chubu National HospitalChubu
  3. 3.Osaka University School of MedicineOsaka
  4. 4.Nihon UniversityNihon
  5. 5.International University of Health and WelfareTokyo
  6. 6.Tokyo Metropolitan Institute of Medical ScienceTokyo
  7. 7.National Children’s HospitalJapan
  8. 8.TokyoJapan

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