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OnabotulinumtoxinA Displays Greater Biological Activity Compared to IncobotulinumtoxinA, Demonstrating Non-Interchangeability in Both In Vitro and In Vivo Assays
Differences in botulinum neurotoxin manufacturing, formulation, and potency evaluation can impact dose and biological activity, which ultimately affect duration of action. The potency of different labeled vials of incobotulinumtoxinA (Xeomin(®); 50 U, 100 U, or 200 U vials; incobotA) versus onabotul...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354455/ https://www.ncbi.nlm.nih.gov/pubmed/32545832 http://dx.doi.org/10.3390/toxins12060393 |
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author | Rupp, David Nicholson, Greg Canty, David Wang, Joanne Rhéaume, Catherine Le, Linh Steward, Lance E. Washburn, Mark Jacky, Birgitte P. Broide, Ron S. Philipp-Dormston, Wolfgang G. Brin, Mitchell F. Brideau-Andersen, Amy |
author_facet | Rupp, David Nicholson, Greg Canty, David Wang, Joanne Rhéaume, Catherine Le, Linh Steward, Lance E. Washburn, Mark Jacky, Birgitte P. Broide, Ron S. Philipp-Dormston, Wolfgang G. Brin, Mitchell F. Brideau-Andersen, Amy |
author_sort | Rupp, David |
collection | PubMed |
description | Differences in botulinum neurotoxin manufacturing, formulation, and potency evaluation can impact dose and biological activity, which ultimately affect duration of action. The potency of different labeled vials of incobotulinumtoxinA (Xeomin(®); 50 U, 100 U, or 200 U vials; incobotA) versus onabotulinumtoxinA (BOTOX(®); 100 U vial; onabotA) were compared on a unit-to-unit basis to assess biological activity using in vitro (light-chain activity high-performance liquid chromatography (LCA-HPLC) and cell-based potency assay (CBPA)) and in vivo (rat compound muscle action potential (CMAP) and mouse digit abduction score (DAS)) assays. Using LCA-HPLC, incobotA units displayed approximately 54% of the protease activity of label-stated equivalent onabotA units. Lower potency, reflected by higher EC(50), ID(50), and ED(50) values (pooled mean ± SEM), was displayed by incobotA compared to onabotA in the CBPA (EC(50): incobotA 7.6 ± 0.7 U/mL; onabotA 5.9 ± 0.5 U/mL), CMAP (ID(50): incobotA 0.078 ± 0.005 U/rat; onabotA 0.053 ± 0.004 U/rat), and DAS (ED(50): incobotA 14.2 ± 0.5 U/kg; onabotA 8.7 ± 0.3 U/kg) assays. Lastly, in the DAS assay, onabotA had a longer duration of action compared to incobotA when dosed at label-stated equivalent units. In summary, onabotA consistently displayed greater biological activity than incobotA in two in vitro and two in vivo assays. Differences in the assay results do not support dose interchangeability between the two products. |
format | Online Article Text |
id | pubmed-7354455 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73544552020-08-05 OnabotulinumtoxinA Displays Greater Biological Activity Compared to IncobotulinumtoxinA, Demonstrating Non-Interchangeability in Both In Vitro and In Vivo Assays Rupp, David Nicholson, Greg Canty, David Wang, Joanne Rhéaume, Catherine Le, Linh Steward, Lance E. Washburn, Mark Jacky, Birgitte P. Broide, Ron S. Philipp-Dormston, Wolfgang G. Brin, Mitchell F. Brideau-Andersen, Amy Toxins (Basel) Article Differences in botulinum neurotoxin manufacturing, formulation, and potency evaluation can impact dose and biological activity, which ultimately affect duration of action. The potency of different labeled vials of incobotulinumtoxinA (Xeomin(®); 50 U, 100 U, or 200 U vials; incobotA) versus onabotulinumtoxinA (BOTOX(®); 100 U vial; onabotA) were compared on a unit-to-unit basis to assess biological activity using in vitro (light-chain activity high-performance liquid chromatography (LCA-HPLC) and cell-based potency assay (CBPA)) and in vivo (rat compound muscle action potential (CMAP) and mouse digit abduction score (DAS)) assays. Using LCA-HPLC, incobotA units displayed approximately 54% of the protease activity of label-stated equivalent onabotA units. Lower potency, reflected by higher EC(50), ID(50), and ED(50) values (pooled mean ± SEM), was displayed by incobotA compared to onabotA in the CBPA (EC(50): incobotA 7.6 ± 0.7 U/mL; onabotA 5.9 ± 0.5 U/mL), CMAP (ID(50): incobotA 0.078 ± 0.005 U/rat; onabotA 0.053 ± 0.004 U/rat), and DAS (ED(50): incobotA 14.2 ± 0.5 U/kg; onabotA 8.7 ± 0.3 U/kg) assays. Lastly, in the DAS assay, onabotA had a longer duration of action compared to incobotA when dosed at label-stated equivalent units. In summary, onabotA consistently displayed greater biological activity than incobotA in two in vitro and two in vivo assays. Differences in the assay results do not support dose interchangeability between the two products. MDPI 2020-06-13 /pmc/articles/PMC7354455/ /pubmed/32545832 http://dx.doi.org/10.3390/toxins12060393 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rupp, David Nicholson, Greg Canty, David Wang, Joanne Rhéaume, Catherine Le, Linh Steward, Lance E. Washburn, Mark Jacky, Birgitte P. Broide, Ron S. Philipp-Dormston, Wolfgang G. Brin, Mitchell F. Brideau-Andersen, Amy OnabotulinumtoxinA Displays Greater Biological Activity Compared to IncobotulinumtoxinA, Demonstrating Non-Interchangeability in Both In Vitro and In Vivo Assays |
title | OnabotulinumtoxinA Displays Greater Biological Activity Compared to IncobotulinumtoxinA, Demonstrating Non-Interchangeability in Both In Vitro and In Vivo Assays |
title_full | OnabotulinumtoxinA Displays Greater Biological Activity Compared to IncobotulinumtoxinA, Demonstrating Non-Interchangeability in Both In Vitro and In Vivo Assays |
title_fullStr | OnabotulinumtoxinA Displays Greater Biological Activity Compared to IncobotulinumtoxinA, Demonstrating Non-Interchangeability in Both In Vitro and In Vivo Assays |
title_full_unstemmed | OnabotulinumtoxinA Displays Greater Biological Activity Compared to IncobotulinumtoxinA, Demonstrating Non-Interchangeability in Both In Vitro and In Vivo Assays |
title_short | OnabotulinumtoxinA Displays Greater Biological Activity Compared to IncobotulinumtoxinA, Demonstrating Non-Interchangeability in Both In Vitro and In Vivo Assays |
title_sort | onabotulinumtoxina displays greater biological activity compared to incobotulinumtoxina, demonstrating non-interchangeability in both in vitro and in vivo assays |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354455/ https://www.ncbi.nlm.nih.gov/pubmed/32545832 http://dx.doi.org/10.3390/toxins12060393 |
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