‘Similar To’ Is Not ‘Identical With’, and ‘Identical With’ Is Not ‘The Same As’

Presently, we have a large number of botulinum neuro-toxins (BoNTs) at our disposal, but in the western hemisphere these are limited almost exclusively to the botulinum toxin A preparations: Abo-(ABO), inco-(INCO), and onabotulinumtoxinA (ONA). Because these are biological preparations, they are never identical to each other, but they are, at most, similar to each other. Their efficacy has been well demonstrated in numerous studies and is undebated [1]. Since their introduction, new batches have repeatedly been made available, and the purity of ABO and ONA has essentially been improved upon. INCO is the most recent formulation and is free of complex proteins. The paper by Frevert [2] in this issue addresses the question of comparability of the three medications, focus-ing mainly on the differential potency between the preparations and on the immunogenicity between them, giving special consideration to the complex neurotoxin accessory proteins (NAPs). It must be emphasized that the author of the publication and the manufacturer of INCO view the lack of these complex proteins as a major distinguishing factor and in fact an advantage to their preparation. The author addresses the topic of complexing proteins in his abstract. Complexing proteins are not covalently bound to the core neurotoxin itself, but are considered a part of the active pharmacological ingredient. Furthermore, after injection of BoNT, complexing proteins are shortly separated from the neurotoxin due to a change in pH and other local environmental factors, thus antibodies against complexing proteins should not inhibit neurotoxin activity. The author further describes differences between the three different products related to their immunogenicity. Until now, there has been no clinical evidence showing significant differences in immunogenicity between ABO, INCO, and ONA [3] Furthermore, differences in assay sensitivity may lead to differences of measured immunogenicity rates, thus no direct comparison can be made today. Further studies encompassing long-term treatment are needed to assess differences of immunogenicity amongst BoNT products. Frevert raises many important considerations relevant to BoNT therapy, although matters of potency require careful interpretation. For example, Frevert states that one study found equivalent potency across ONA and INCO [4], in an assay that in fact was developed by Dr. Frevert and is used by the company. However, the author fails to consider contrasting results by Hunt who established potency differences between the two products using two independent assays—an LD50 and also a SNAP-25 cleavage [5, 6]. The different results across these studies indicate underlying …