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Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD): safety and efficacy in adults treated for 30 months

Olipudase alfa, a recombinant human acid sphingomyelinase (ASM), is an enzyme replacement therapy for the treatment of nonneurologic manifestations of acid sphingomyelinase deficiency (ASMD). This ongoing, open-label, long-term study (NCT02004704) assessed safety and efficacy of olipudase alfa follo...

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Autores principales: Wasserstein, Melissa P., Diaz, George A., Lachmann, Robin H., Jouvin, Marie-Hélène, Nandy, Indrani, Ji, Allena J., Puga, Ana Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133173/
https://www.ncbi.nlm.nih.gov/pubmed/29305734
http://dx.doi.org/10.1007/s10545-017-0123-6
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author Wasserstein, Melissa P.
Diaz, George A.
Lachmann, Robin H.
Jouvin, Marie-Hélène
Nandy, Indrani
Ji, Allena J.
Puga, Ana Cristina
author_facet Wasserstein, Melissa P.
Diaz, George A.
Lachmann, Robin H.
Jouvin, Marie-Hélène
Nandy, Indrani
Ji, Allena J.
Puga, Ana Cristina
author_sort Wasserstein, Melissa P.
collection PubMed
description Olipudase alfa, a recombinant human acid sphingomyelinase (ASM), is an enzyme replacement therapy for the treatment of nonneurologic manifestations of acid sphingomyelinase deficiency (ASMD). This ongoing, open-label, long-term study (NCT02004704) assessed safety and efficacy of olipudase alfa following 30 months of treatment in five adult patients with ASMD. There were no deaths, serious or severe events, or discontinuations during 30 months of treatment. The majority of adverse events were mild and included headache, nausea, and abdominal pain. No patient developed anti-drug antibodies and there were no clinically significant adverse changes in vital signs, hematology, or cardiac safety parameters. Statistically significant reductions in liver (31%) and spleen (39%) volumes were maintained through 30 months of treatment. There was a mean increase in lung diffusing capacity of 35%, and clinically relevant improvements in infiltrative lung disease parameters. Lipid profiles improved in all patients. Improvements in bone mineral density of the spine were observed in some patients. Chitotriosidase in serum and lyso-sphingomyelin in dried blood spots decreased with olipudase alfa treatment, suggesting utility as biomarkers for monitoring treatment efficacy. Olipudase alfa is the first etiology-specific treatment in development for ASMD. This study demonstrates that treatment with olipudase alfa for 30 months is well-tolerated and associated with life-transforming sustained improvements in relevant disease clinical measures. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10545-017-0123-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-61331732018-09-14 Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD): safety and efficacy in adults treated for 30 months Wasserstein, Melissa P. Diaz, George A. Lachmann, Robin H. Jouvin, Marie-Hélène Nandy, Indrani Ji, Allena J. Puga, Ana Cristina J Inherit Metab Dis Original Article Olipudase alfa, a recombinant human acid sphingomyelinase (ASM), is an enzyme replacement therapy for the treatment of nonneurologic manifestations of acid sphingomyelinase deficiency (ASMD). This ongoing, open-label, long-term study (NCT02004704) assessed safety and efficacy of olipudase alfa following 30 months of treatment in five adult patients with ASMD. There were no deaths, serious or severe events, or discontinuations during 30 months of treatment. The majority of adverse events were mild and included headache, nausea, and abdominal pain. No patient developed anti-drug antibodies and there were no clinically significant adverse changes in vital signs, hematology, or cardiac safety parameters. Statistically significant reductions in liver (31%) and spleen (39%) volumes were maintained through 30 months of treatment. There was a mean increase in lung diffusing capacity of 35%, and clinically relevant improvements in infiltrative lung disease parameters. Lipid profiles improved in all patients. Improvements in bone mineral density of the spine were observed in some patients. Chitotriosidase in serum and lyso-sphingomyelin in dried blood spots decreased with olipudase alfa treatment, suggesting utility as biomarkers for monitoring treatment efficacy. Olipudase alfa is the first etiology-specific treatment in development for ASMD. This study demonstrates that treatment with olipudase alfa for 30 months is well-tolerated and associated with life-transforming sustained improvements in relevant disease clinical measures. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10545-017-0123-6) contains supplementary material, which is available to authorized users. Springer Netherlands 2018-01-05 2018 /pmc/articles/PMC6133173/ /pubmed/29305734 http://dx.doi.org/10.1007/s10545-017-0123-6 Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Wasserstein, Melissa P.
Diaz, George A.
Lachmann, Robin H.
Jouvin, Marie-Hélène
Nandy, Indrani
Ji, Allena J.
Puga, Ana Cristina
Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD): safety and efficacy in adults treated for 30 months
title Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD): safety and efficacy in adults treated for 30 months
title_full Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD): safety and efficacy in adults treated for 30 months
title_fullStr Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD): safety and efficacy in adults treated for 30 months
title_full_unstemmed Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD): safety and efficacy in adults treated for 30 months
title_short Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD): safety and efficacy in adults treated for 30 months
title_sort olipudase alfa for treatment of acid sphingomyelinase deficiency (asmd): safety and efficacy in adults treated for 30 months
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133173/
https://www.ncbi.nlm.nih.gov/pubmed/29305734
http://dx.doi.org/10.1007/s10545-017-0123-6
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