Preclinical update on BOTOX® (botulinum toxin type A)-purified neurotoxin complex relative to other botulinurn neurotoxin preparations

ABSTRACT

Ongoing investigations evaluated clinically relevant properties of BOTOX® (botulinum toxin type A) relative to other botulinum neurotoxin preparations based on the same (type A) or different (types B, C, E and F) serotypes. The mouse Digit Abduction Scoring (DAS) assay was used to compare muscle weakening efficacy, the antigenic potential of two BOTOX® preparations was measured in rabbits, and the presence of antibodies to serotypes A and B was analysed in humans. BOTOX® and new BOTOX® produced similar degrees of dose-related muscle weakness in mice. Both preparations of BOTOX® were approximately four times more potent than Dysport®. Preparations of serotypes B, C, and F also demonstrated lower potency than BOTOX®, with serotype F also having a shorter duration of action. Neutralising antibodies were found in rabbits 3 months post-treatment with BOTOX®, but were undetected 8 months post-treatment with new BOTOX®. A high incidence of antibodies to type B was observed in individuals with no known exposure to type B toxin: highest in groups with the highest incidence of type A antibodies. The safety margin for BOTOX®, calculated using DAS median effective dose (ED,) and the minimum dose producing a 10% reduction in body weight, was more than twice that of Dysport®. In conclusion, each botulinum toxin serotype tested exhibited a different muscle weakening efficacy; BOTOX® consistently exhibited the greatest eficacy. Importantly, BOTOX® and Dysport® exhibited markedly different efficacy and safety profiles, and should not be considered interchangeable. Antibody distribution in humans suggests that there may be immunological cross-reactivity between serotypes A and B.