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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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