Long-term effectiveness of agalsidase alfa enzyme replacement in Fabry disease: A Fabry Outcome Survey analysis

Michael Beck; Derralynn Hughes; Christoph Kampmann; Sylvain Larroque; Atul Mehta; Guillem Pintos-Morell; Uma Ramaswami; Michael West; Anna Wijatyk; Roberto Giugliani

doi:10.1016/j.ymgmr.2015.02.002

Long-term effectiveness of agalsidase alfa enzyme replacement in Fabry disease: A Fabry Outcome Survey analysis

Michael Beck, Derralynn Hughes, Christoph Kampmann, Sylvain Larroque, Atul Mehta, Guillem Pintos-Morell, Uma Ramaswami, Michael West, Anna Wijatyk, Roberto Giugliani

Medicine

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107 Citations (Scopus)

Abstract

Outcomes from 5 years of treatment with agalsidase alfa enzyme replacement therapy (ERT) for Fabry disease in patients enrolled in the Fabry Outcome Survey (FOS) were compared with published findings for untreated patients with Fabry disease. Data were extracted from FOS, a Shire-sponsored database, for comparison with data from three published studies. Outcomes evaluated were the annualized rate of change in estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) as well as time to and ages at a composite morbidity endpoint and at death. FOS data were extracted for 740 treated patients who were followed for a median of ∼ 5 years. Compared with no treatment, patients treated with agalsidase alfa demonstrated slower decline in renal function and slower progression of left ventricular hypertrophy. Treated male patients with baseline eGFR < 60 mL/min/1.73 m² had a mean (standard error of the mean [SEM]) annualized change in eGFR of - 2.86 (0.53) mL/min/1.73 m²/y compared with - 6.8 (1.5) in the published untreated cohort. The mean (SEM) rate of LVMI increase with treatment was 0.33 (0.10) g/m^2.7/y in males and 0.48 (0.09) in females, compared with 4.07 (1.03) in untreated males and 2.31 (0.81) in untreated females. Morbidity occurred later in treated patients, with ∼ 16% risk of a composite morbidity event (26% in males) after 24 months with ERT versus ∼ 45% without treatment, with first events and deaths also occurring at older ages in patients administered ERT (e.g., estimated median survival in treated males was 77.5 years versus 60 years in untreated males). Findings from these retrospective comparisons of observational data and published literature support the long-term benefits of ERT with agalsidase alfa for Fabry disease in slowing the progression of renal impairment and cardiomyopathy. Treatment also appeared to delay the onset of morbidity and mortality. Interpretation of these findings should take into account that they are based on retrospective comparisons with previously published data.

Original language	English
Pages (from-to)	21-27
Number of pages	7
Journal	Molecular Genetics and Metabolism Reports
Volume	3
DOIs	https://doi.org/10.1016/j.ymgmr.2015.02.002
Publication status	Published - Jun 1 2015

Bibliographical note

Funding Information:
Michael Beck and Atul Mehta have received honoraria, travel support, and unrestricted grants from Actelion, BioMarin, Genzyme, and Shire. Derralynn Hughes has received travel and research grants and honoraria for speaking and consulting from Amicus, Genzyme/Sanofi, Protalix, and Shire. Guillem Pintos-Morell has received honoraria and travel support from Shire and travel support from BioMarin and Genzyme. Uma Ramaswami has received travel and research grants and honoraria for lectures from Genzyme and Shire. Christoph Kampmann has received honoraria for lectures and travel support from Actelion, BioMarin, Genzyme, Gore, and Shire. Anna Wijatyk is an employee of and owns shares in Shire, and Sylvain Larroque was an employee of Shire at the time this work was done. Roberto Giugliani has received consulting fees from Amicus, BioMarin, Genzyme, Shire, and Synageva; participated in clinical trials sponsored by Amicus, BioMarin, Genzyme, GlaxoSmithKline, Shire, and Synageva; and assisted in the design of and/or participated in clinical studies using products manufactured by Actelion, BioMarin, Genzyme, and Shire. Michael West has received research funds, consulting fees, speaker fees, and/or travel support from Actelion, Amicus, Excelsior, Genzyme, GlaxoSmithKline, Shire, Sumitomo, and Synageva.

Publisher Copyright:
© 2015 The Authors. Published by Elsevier Inc.

ASJC Scopus Subject Areas

Molecular Biology
Genetics
Endocrinology

PubMed: MeSH publication types

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10.1016/j.ymgmr.2015.02.002

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title = "Long-term effectiveness of agalsidase alfa enzyme replacement in Fabry disease: A Fabry Outcome Survey analysis",

abstract = "Outcomes from 5 years of treatment with agalsidase alfa enzyme replacement therapy (ERT) for Fabry disease in patients enrolled in the Fabry Outcome Survey (FOS) were compared with published findings for untreated patients with Fabry disease. Data were extracted from FOS, a Shire-sponsored database, for comparison with data from three published studies. Outcomes evaluated were the annualized rate of change in estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) as well as time to and ages at a composite morbidity endpoint and at death. FOS data were extracted for 740 treated patients who were followed for a median of ∼ 5 years. Compared with no treatment, patients treated with agalsidase alfa demonstrated slower decline in renal function and slower progression of left ventricular hypertrophy. Treated male patients with baseline eGFR < 60 mL/min/1.73 m2 had a mean (standard error of the mean [SEM]) annualized change in eGFR of - 2.86 (0.53) mL/min/1.73 m2/y compared with - 6.8 (1.5) in the published untreated cohort. The mean (SEM) rate of LVMI increase with treatment was 0.33 (0.10) g/m2.7/y in males and 0.48 (0.09) in females, compared with 4.07 (1.03) in untreated males and 2.31 (0.81) in untreated females. Morbidity occurred later in treated patients, with ∼ 16% risk of a composite morbidity event (26% in males) after 24 months with ERT versus ∼ 45% without treatment, with first events and deaths also occurring at older ages in patients administered ERT (e.g., estimated median survival in treated males was 77.5 years versus 60 years in untreated males). Findings from these retrospective comparisons of observational data and published literature support the long-term benefits of ERT with agalsidase alfa for Fabry disease in slowing the progression of renal impairment and cardiomyopathy. Treatment also appeared to delay the onset of morbidity and mortality. Interpretation of these findings should take into account that they are based on retrospective comparisons with previously published data.",

author = "Michael Beck and Derralynn Hughes and Christoph Kampmann and Sylvain Larroque and Atul Mehta and Guillem Pintos-Morell and Uma Ramaswami and Michael West and Anna Wijatyk and Roberto Giugliani",

note = "Funding Information: Michael Beck and Atul Mehta have received honoraria, travel support, and unrestricted grants from Actelion, BioMarin, Genzyme, and Shire. Derralynn Hughes has received travel and research grants and honoraria for speaking and consulting from Amicus, Genzyme/Sanofi, Protalix, and Shire. Guillem Pintos-Morell has received honoraria and travel support from Shire and travel support from BioMarin and Genzyme. Uma Ramaswami has received travel and research grants and honoraria for lectures from Genzyme and Shire. Christoph Kampmann has received honoraria for lectures and travel support from Actelion, BioMarin, Genzyme, Gore, and Shire. Anna Wijatyk is an employee of and owns shares in Shire, and Sylvain Larroque was an employee of Shire at the time this work was done. Roberto Giugliani has received consulting fees from Amicus, BioMarin, Genzyme, Shire, and Synageva; participated in clinical trials sponsored by Amicus, BioMarin, Genzyme, GlaxoSmithKline, Shire, and Synageva; and assisted in the design of and/or participated in clinical studies using products manufactured by Actelion, BioMarin, Genzyme, and Shire. Michael West has received research funds, consulting fees, speaker fees, and/or travel support from Actelion, Amicus, Excelsior, Genzyme, GlaxoSmithKline, Shire, Sumitomo, and Synageva. Publisher Copyright: {\textcopyright} 2015 The Authors. Published by Elsevier Inc.",

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doi = "10.1016/j.ymgmr.2015.02.002",

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T1 - Long-term effectiveness of agalsidase alfa enzyme replacement in Fabry disease

T2 - A Fabry Outcome Survey analysis

AU - Beck, Michael

AU - Hughes, Derralynn

AU - Kampmann, Christoph

AU - Larroque, Sylvain

AU - Mehta, Atul

AU - Pintos-Morell, Guillem

AU - Ramaswami, Uma

AU - West, Michael

AU - Wijatyk, Anna

AU - Giugliani, Roberto

N1 - Funding Information: Michael Beck and Atul Mehta have received honoraria, travel support, and unrestricted grants from Actelion, BioMarin, Genzyme, and Shire. Derralynn Hughes has received travel and research grants and honoraria for speaking and consulting from Amicus, Genzyme/Sanofi, Protalix, and Shire. Guillem Pintos-Morell has received honoraria and travel support from Shire and travel support from BioMarin and Genzyme. Uma Ramaswami has received travel and research grants and honoraria for lectures from Genzyme and Shire. Christoph Kampmann has received honoraria for lectures and travel support from Actelion, BioMarin, Genzyme, Gore, and Shire. Anna Wijatyk is an employee of and owns shares in Shire, and Sylvain Larroque was an employee of Shire at the time this work was done. Roberto Giugliani has received consulting fees from Amicus, BioMarin, Genzyme, Shire, and Synageva; participated in clinical trials sponsored by Amicus, BioMarin, Genzyme, GlaxoSmithKline, Shire, and Synageva; and assisted in the design of and/or participated in clinical studies using products manufactured by Actelion, BioMarin, Genzyme, and Shire. Michael West has received research funds, consulting fees, speaker fees, and/or travel support from Actelion, Amicus, Excelsior, Genzyme, GlaxoSmithKline, Shire, Sumitomo, and Synageva. Publisher Copyright: © 2015 The Authors. Published by Elsevier Inc.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - Outcomes from 5 years of treatment with agalsidase alfa enzyme replacement therapy (ERT) for Fabry disease in patients enrolled in the Fabry Outcome Survey (FOS) were compared with published findings for untreated patients with Fabry disease. Data were extracted from FOS, a Shire-sponsored database, for comparison with data from three published studies. Outcomes evaluated were the annualized rate of change in estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) as well as time to and ages at a composite morbidity endpoint and at death. FOS data were extracted for 740 treated patients who were followed for a median of ∼ 5 years. Compared with no treatment, patients treated with agalsidase alfa demonstrated slower decline in renal function and slower progression of left ventricular hypertrophy. Treated male patients with baseline eGFR < 60 mL/min/1.73 m2 had a mean (standard error of the mean [SEM]) annualized change in eGFR of - 2.86 (0.53) mL/min/1.73 m2/y compared with - 6.8 (1.5) in the published untreated cohort. The mean (SEM) rate of LVMI increase with treatment was 0.33 (0.10) g/m2.7/y in males and 0.48 (0.09) in females, compared with 4.07 (1.03) in untreated males and 2.31 (0.81) in untreated females. Morbidity occurred later in treated patients, with ∼ 16% risk of a composite morbidity event (26% in males) after 24 months with ERT versus ∼ 45% without treatment, with first events and deaths also occurring at older ages in patients administered ERT (e.g., estimated median survival in treated males was 77.5 years versus 60 years in untreated males). Findings from these retrospective comparisons of observational data and published literature support the long-term benefits of ERT with agalsidase alfa for Fabry disease in slowing the progression of renal impairment and cardiomyopathy. Treatment also appeared to delay the onset of morbidity and mortality. Interpretation of these findings should take into account that they are based on retrospective comparisons with previously published data.

AB - Outcomes from 5 years of treatment with agalsidase alfa enzyme replacement therapy (ERT) for Fabry disease in patients enrolled in the Fabry Outcome Survey (FOS) were compared with published findings for untreated patients with Fabry disease. Data were extracted from FOS, a Shire-sponsored database, for comparison with data from three published studies. Outcomes evaluated were the annualized rate of change in estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) as well as time to and ages at a composite morbidity endpoint and at death. FOS data were extracted for 740 treated patients who were followed for a median of ∼ 5 years. Compared with no treatment, patients treated with agalsidase alfa demonstrated slower decline in renal function and slower progression of left ventricular hypertrophy. Treated male patients with baseline eGFR < 60 mL/min/1.73 m2 had a mean (standard error of the mean [SEM]) annualized change in eGFR of - 2.86 (0.53) mL/min/1.73 m2/y compared with - 6.8 (1.5) in the published untreated cohort. The mean (SEM) rate of LVMI increase with treatment was 0.33 (0.10) g/m2.7/y in males and 0.48 (0.09) in females, compared with 4.07 (1.03) in untreated males and 2.31 (0.81) in untreated females. Morbidity occurred later in treated patients, with ∼ 16% risk of a composite morbidity event (26% in males) after 24 months with ERT versus ∼ 45% without treatment, with first events and deaths also occurring at older ages in patients administered ERT (e.g., estimated median survival in treated males was 77.5 years versus 60 years in untreated males). Findings from these retrospective comparisons of observational data and published literature support the long-term benefits of ERT with agalsidase alfa for Fabry disease in slowing the progression of renal impairment and cardiomyopathy. Treatment also appeared to delay the onset of morbidity and mortality. Interpretation of these findings should take into account that they are based on retrospective comparisons with previously published data.

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Long-term effectiveness of agalsidase alfa enzyme replacement in Fabry disease: A Fabry Outcome Survey analysis

Abstract

Bibliographical note

ASJC Scopus Subject Areas

PubMed: MeSH publication types

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