INTRODUCTION
Characteristics of IncobotulinumtoxinA
IncobotulinumtoxinA (Xeomin®/Xeomeen®/Bocouture®/XEOMIN Cosmetic™; Merz Pharmaceuticals GmbH, Germany), along with onabotulinumtoxinA (BOTOX®/BOTOX® Cosmetic/Vistabel®; Allergan, Irvine, CA, USA) and abobotulinumtoxinA (Dysport®; Ipsen Ltd, Slough, Berkshire, UK / Azzalure®; Galderma UK Ltd, Watford, Hertfordshire, UK), is derived from the Hall strain of the anaerobic bacterium Clostridium botulinum type A. However, incobotulinumtoxinA is a formulation of botulinum neurotoxin type A that has undergone a purification processes that separates the 150-kDa neurotoxin from the high-molecular-weight (900 kDa) complex.1,2 Therefore, the active ingredient of incobotulinumtoxinA represents the pure neurotoxin (150 kDa) that is free from complexing proteins.1 In this respect, incobotulinumtoxinA differs from onabotulinumtoxinA and abobotulinumtoxinA, which both contain complexing proteins. IncobotulinumtoxinA is licensed in the United States, Canada, all major European countries, Argentina, and South Korea for the treatment of glabellar frown lines (GFL); in Russia and Mexico it is licensed for the treatment of mimic wrinkles and hyperkinetic facial lines, respectively.
In a study by Frevert to determine the amount of neurotoxin present in pharmaceutical preparations of incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA, the mean concentrations were observed to be 0.44 ng/100 U, 0.73 ng/100 U, and 0.65 ng/100 U, respectively. IncobotulinumtoxinA contains no other clostridial proteins, and, therefore, the specific biologic potency relative to the total foreign protein is 227 U/ng. Since the reported clostridial protein content per 100 U of onabotulinumtoxinA is 5 ng and of abobotulinumtoxinA is 0.87 ng, the equivalent specific biologic potency relative to the total foreign-protein load for onabotulinumtoxinA is 20 U/ng and for abobotulinumtoxinA is 115 U/ng.3 Thus, the foreign-protein load delivered per unit of incobotulinumtoxinA is lower than that for both onabotulinumtoxinA and abobotulinumtoxinA.
Complexing proteins protect the neurotoxin from harsh environmental conditions (such as low gastric pH) after oral ingestion.4,5 However, whether or not they are useful in commercially available preparations of botulinum neurotoxin serotype A (BoNT/A) is disputed as complexing proteins play no role in the clinical or therapeutic efficacy of BoNT/A. In real-time and accelerated-stability studies, incobotulinumtoxinA was stable without refrigeration for 48 months and was unaffected by short-term temperature stress up to 60°C, suggesting that a role for complexing proteins in stabilizing the neurotoxin outside the intestine is unlikely.6 Furthermore, rapid dissociation of the BoNT/A complexes in onabotulinumtoxinA and abobotulinumtoxinA occurs at a neutral physiological pH, with a release of up to 80% of neurotoxin within 1 minute at neutral pH.7 Such rapid dissociation at normal physiologic pH suggests that the complexing proteins cannot protect the neurotoxin postinjection, or limit its spread.
Spread of Effect/Field of Efficacy
The spread of different BoNT/A preparations is of crucial clinical relevance, especially in esthetics, where precise localization of the clinical effect is essential to avoid adverse events (AEs) caused by movement beyond the target muscle.8 Six weeks after injection of dosages in line with those recommended for the treatment of GFL,9-11 the mean maximal areas of anhidrosis (indicating the size of the field of efficacy) for incobotulinumtoxinA (5 U), onabotulinumtoxinA (5 U), and abobotulinumtoxinA (12.5 U) were 364.3 ± 138.1, 343.1 ± 110.7, and 459.1 ± 151.8 mm2, respectively.8 The maximal area of anhidrosis for inco-
