AbobotulinumtoxinA, onabotulinumtoxinA and incobotulinumtoxinA neurotoxin content and activity: Potential implications for duration of efficacy in patients (P5.6-018)

Objective: To quantify the amount of botulinum neurotoxin-A (BoNT-A) protein in each vial of commercial BoNT-A product and compare light chain activity of 150 kDa BoNT-A in different products. Background: Therapeutic BoNT-A effects are mediated by the 150 kDa neurotoxin. Each product has a unique manufacturing process, different excipients, potency units and dosing recommendations. For example, the (US FDA) maximum total dose for use in adult upper limb (AUL) spasticity is 1000U for abobotulinumtoxinA (Dysport) 1000U, 400U for onabotulinumtoxinA (Botox), and 400U for incobotulinumtoxinA (Xeomin). Light chain activity of 150 kDa BoNT-A in different products is unknown. Design/Methods: Quantitation of 150 kDa BoNT-A used sandwich ELISA with antibodies specific to 150 kDa BoNT-A. Commercial products were quantitated versus a calibration curve of recombinant BoNT-A. Activity was assessed using EndoPep assay. Concentration of a cleaved target was measured and quantity of 150 kDa BoNT-A determined relative to quantity of recombinant BoNT-A required for equivalent light chain activity. Results: The amount of 150 kDa neurotoxin per potency unit of commercial product was 5.38pg for abobotulinumtoxinA, 9.04pg for onabotulinumtoxinA and 4.03pg for incobotulinumtoxinA. Thus, when total recommended AUL doses are given, there is more 150 kDa BoNT-A injected in abobotulinumtoxinA (1000U × 5.38pg = 5.38ng) than in onabotulinumtoxinA (400U × 9.04pg = 3.62ng) and incobotulinumtoxinA (400U × 4.03 = 1.61ng). EndoPep assay showed no significant differences between BoNT-A products in light chain activity per ng of 150 kDa toxin. Conclusions: No differences in light chain activity were seen between BoNT-A products. However, there were greater amounts of neurotoxin in abobotulinumtoxinA at the recommended AUL dose than either onabotulinumtoxinA or incobotulinumtoxinA. At the recommended dose, all BoNT-A products have a similar safety profile. This greater amount of neurotoxin may prolong denervation following abobotulinumtoxinA injection, resulting in the previously observed clinically longer duration of response with sustained symptom relief between injections. Disclosure: Dr. Field has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ipsen. Dr. Splevins has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ipsen. Dr. van der Schans has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with TNO – CBRN Protection. Dr. van der Schans has received research support from Ipsen Bioinnovation. Dr. Langenberg has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with TNO – CBRN Protection. Dr. Langenberg has received research support from Ipsen Bioinnovation. Dr. Noort has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with TNO – CBRN Protection. Dr. Noort has received research support from Ipsen Bioinnovation. Dr. Picaut has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ipsen. Dr. Foster has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ipsen.