Clinical and pharmacological properties of incobotulinumtoxinA and its use in neurological disorders

Abstract

BackgroundIncobotulinumtoxinA (Xeomin®) is a purified botulinum neurotoxin type A formulation, free from complexing proteins, with proven efficacy and good tolerability for the treatment of neurological conditions such as blepharospasm, cervical dystonia (CD), and post-stroke spasticity of the upper limb. This article provides a comprehensive overview of incobotulinumtoxinA based on randomized controlled trials and prospective clinical studies.SummaryIncobotulinumtoxinA provides clinical efficacy in treating blepharospasm, CD, and upper-limb post-stroke spasticity based on randomized, double-blind, placebo-controlled trials with open-label extension periods (total study duration up to 89 weeks). Adverse events were generally mild or moderate. The most frequent adverse events, probably related to the injections, included eyelid ptosis and dry eye in the treatment of blepharospasm, dysphagia, neck pain, and muscular weakness in patients with CD, and injection site pain and muscular weakness when used for treating spasticity. In blepharospasm and CD, incobotulinumtoxinA was investigated in clinical trials permitting flexible intertreatment intervals based on the individual patient’s clinical need; the safety profile of intervals shorter than 12 weeks was comparable to intervals of 12 weeks and longer. There were no cases of newly formed neutralizing antibodies during the Phase III and IV incobotulinumtoxinA trials. Phase III head-to-head trials of incobotulinumtoxinA versus onabotulinumtoxinA for the treatment of blepharospasm and CD have demonstrated therapeutic equivalence of both formulations. Additional Phase III trials of incobotulinumtoxinA in conditions such as lower-limb spasticity, spasticity in children with cerebral palsy, and sialorrhea in various neurological disorders are ongoing.ConclusionIncobotulinumtoxinA is an effective, well-tolerated botulinum neurotoxin type A formulation. Data from randomized clinical trials and further observational studies are expected to help physicians to optimize treatment by tailoring the choice of formulation, dose, and treatment intervals to the patient’s clinical needs.

Botulinum Toxin in Aesthetic Medicine: Myths and Realities

“… 35 Xeomin is reported to be free from complexing proteins (although the manufacturer, Merz, has not published suitable data to substantiate this claim). 36 However, 2 protein loads for Xeomin have been published: 0.6 37 and 0.44 ng per 100-unit vial, 38 an interesting difference that has been criticized. 39 …”

“… 27 Against this background, whether the lack of complexing proteins in Xeomin confers a therapeutic advantage is not yet established, and long-term comparative studies are still needed, despite the product being available for a decade. 25 , 36 However, based on the lack of marked differences in either immunogenicity (discussed below) or the field of effect, 10 , 20 – 23 , 41 , 42 the discordance in protein load between contemporary BoNT formulations seems clinically irrelevant in aesthetic applications, where very low doses of the products are used.…”

Septins: Regulators of Protein Stability

“…On the other hand, the remarkable stability of LCA is fundamental in the success of BoNT/A for long-term treatment of several disorders as well as cosmetic therapies (Bhidayasiri and Truong, 2005; Chancellor et al, 2013; Esquenazi et al, 2013; Hallett et al, 2013; Naumann et al, 2013; Jost et al, 2015; Choi et al, 2016), and a super-stable LCA would be useful therapeutically.…”

Incobotulinumtoxin A for Sialorrhea in Neurological Disorders: A Real-Life Experience

“…It can also be stored at room temperatures <25 °C [ 23 ]. Routine use of inco-A showed efficacy and safety in a variety of disorders [ 22 , 24 , 25 , 26 ]. The use of inco-A for the treatment of sialorrhea in neurological diseases is controversial, with some studies showing efficacy [ 27 ], and others showing no significant differences with a placebo [ 28 ].…”