A Preclinical Study Comparing the Activity and Potency of OnabotulinumtoxinA and PrabotulinumtoxinA

David C Rupp; David Canty; Catherine Rhéaume; Birgitte Sondergaard; Celina Niño; Ron S Broide; Amy D Brideau-Andersen

doi:10.2147/CCID.S397999

A Preclinical Study Comparing the Activity and Potency of OnabotulinumtoxinA and PrabotulinumtoxinA

Clin Cosmet Investig Dermatol. 2023 Mar 8:16:581-591. doi: 10.2147/CCID.S397999. eCollection 2023.

Authors

David C Rupp¹, David Canty¹, Catherine Rhéaume¹, Birgitte Sondergaard¹, Celina Niño¹, Ron S Broide¹, Amy D Brideau-Andersen¹

Affiliation

¹ Allergan Aesthetics, an AbbVie Company, Irvine, CA, USA.

Abstract

Objective: The goal of this study was to compare the unit-to-unit biological activity of the vacuum-dried formulation of prabotulinumtoxinA (prabotA) and onabotulinumtoxinA (onabotA) in preclinical assays.

Methods: Reconstituted 100 U vials of prabotA and onabotA were tested in 3 distinct assays: plate-capture light chain activity (PC-LCA), measuringlight chain enzymatic activity after recovery of toxin from reconstituted product using a proprietary toxin capture step; cell-based potency assay (CBPA), measuring the intoxication steps of binding, translocation, and light chain activity (synaptosomal-associated protein 25 [SNAP25] cleavage); and mouse Digit Abduction Score (DAS), evaluating muscle paresis. Each assay tested 3 separate prabotA and onabotA lots on several independent test dates.

Results: Multiple orthogonal assays established that when assessed on a unit-to-unit basis, the biological activity of prabotA is lower than that of onabotA. In the PC-LCA and CBPA assays, onabotA displayed 1.51 ± 0.14-fold higher (mean ± SD) and 1.33 ± 0.07-fold higher (mean of pooled lots ± SEM) activity than prabotA, respectively. Similarly, the mouse DAS data showed that onabotA had 1.4 ± 0.1-fold higher (mean ± SEM) potency than prabotA. Results of all 3 assays demonstrated differences in potency, efficacy, and duration of action between onabotA and prabotA on a unit-to-unit basis.

Conclusion: Preclinical assays established differences in the biological activity of onabotA and prabotA, supporting that the units of biological activity are not interchangeable.

Keywords: animal studies; biological assays; enzyme assays; motor neurons; pharmaceutical preparations; protein binding.

Grants and funding

Allergan Aesthetics, an AbbVie Company, funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided to the authors by Regina Kelly, MA of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, and was funded by AbbVie.