Abstract
Objectives: In a multicenter, open-label, treatment protocol (HGT-REP-059; NCT01031173), clinical effects and tolerability of agalsidase alfa (agalα; 0.2 mg/kg every other week) were evaluated in patients with Fabry disease who were treatment naïve or switched from agalsidase beta (switch). Over 24 months, data were collected on the safety profile; renal and cardiac parameters were assessed using estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMI), and midwall fractional shortening (MFS).
Results: Enrolled patients included 71 switch (median [range] age, 46.6 [5–84] years; male to female [M:F], 40:31) and 29 treatment naïve (38.7 [12–74] years; M:F, 14:15). Adverse events (AEs) were consistent with the known safety profile of agalα. Two switch patients had hospitalization due to possibly/probably drug-related serious AEs (one with transient ischemic attack, one with infusion-related AEs). One switch and two treatment-naïve patients discontinued treatment because of AEs. Three patients (one each switch, treatment naïve, and previous agalα) died; no deaths were considered drug-related. There was no significant change from baseline in LVMI or MFS in either group. Similarly, eGFR remained stable; mean ± standard error annualized change in eGFR (mL/min/1.73 m2) was −2.40 ± 1.04 in switch and −1.68 ± 2.21 in treatment-naïve patients.
Conclusions: This is the largest cohort of patients with Fabry disease who were started on or switched to agalα in an FDA-accepted protocol during a worldwide supply shortage of agalsidase beta. Because this protocol was primarily designed to provide access to agalα, there were limitations, including not having stringent selection criteria and the lack of a placebo group.
Competing interests: None declared
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Acknowledgments
This study was funded by Shire. The authors thank Drs Bruce A. Barshop, Ellen Boyd, Alpana Desai, Richard Forte, Myrl Holida, Richard Hillman, Jennifer Ibrahim, Rebecca Mardach, Barbara Rever, and Neal Weinreb for their contributions to data collection and input for study HGT-REP-059. Medical writing support for this manuscript was provided by Ray Beck, Jr, PhD, and Margit Rezabek, DVM, PhD, of Excel Scientific Solutions, which was funded by Shire.
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Communicated by: Markus Ries, MD, PhD, MHSc, FCP
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Synopsis
In this cohort of patients with Fabry disease who were treatment naïve or switched from agalβ, agalα was generally well tolerated and stabilized renal and cardiac parameters.
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Conflicts of Interest
Ozlem Goker-Alpan has received research support from Actelion, Shire, Genzyme Corp, Amicus, and Pfizer-Protalix Biotherapeutics, as well as payments for consultancy from Actelion, Shire, and Pfizer-Protalix Biotherapeutics and payments for speaker bureaus from Actelion, Genzyme Corp, and Shire.
Suma P. Shankar has been site primary investigator in clinical trials and received research support and educational grants from Genzyme, Shire, Protalix, Actelion, and Amicus and has served on speakers bureaus for Genzyme and Shire.
Yeong-Hau H. Lien has received research support from Shire.
Neal Weinreb has received research support and honoraria from Genzyme-Sanofi and Shire and has served on advisory boards for Genzyme-Sanofi, Shire, and Pfizer-Protalix Biotherapeutics and served on speakers bureaus for Genzyme-Sanofi, Actelion, Shire, and Pfizer.
Anna Wijatyk, Peter Chang, and Rick Martin are employees of and hold stock options in Shire.
Khan Nedd declares no potential competing interests.
Patient Consent Statement
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.
Details of the Contributions of Individual Authors
Anna Wijatyk, Peter Chang, and Rick Martin were involved in the study planning. Ozlem Goker-Alpan was the Principal Investigator and signed off on the protocol. Ozlem Goker-Alpan, Khan Nedd, Suma P. Shankar, Yeong-Hau Lien, and Neal Weinreb were involved in the study conduct. Peter Chang conducted the statistical analyses. All authors contributed to the first draft of the manuscript, were involved in the critical review and revision of subsequent drafts, and approved the final draft for submission.
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Goker-Alpan, O. et al. (2015). Effect and Tolerability of Agalsidase Alfa in Patients with Fabry Disease Who Were Treatment Naïve or Formerly Treated with Agalsidase Beta or Agalsidase Alfa. In: Zschocke, J., Baumgartner, M., Morava, E., Patterson, M., Rahman, S., Peters, V. (eds) JIMD Reports, Volume 23. JIMD Reports, vol 23. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_422
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DOI: https://doi.org/10.1007/8904_2015_422
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