IncobotulinumtoxinA: A Highly Purified and Precisely Manufactured Botulinum Neurotoxin Type A

January 2019 | Volume 18 | Issue 1 | Original Article | 52 | Copyright © January 2019

Martina Kerscher MD PhD,a Rungsima Wanitphakdeedecha MD MA MSc,b Ada Trindade de Almeida MD,c Corey Maas MD FACS,d and Jürgen Frevert PhDe

aDepartment of Cosmetic Science, University of Hamburg, Hamburg, Germany bDepartment of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand cClinica de Dermatologia, Hospital do Servidor Municipal de São Paulo, São Paulo, Brazil dOtolaryngology and Head and Neck Surgery, University of California, San Francisco, CA eFormerly of Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany

Figure 2tions.59,60 DaxibotulinumtoxinA contains the purified 150 kDa BoNT-A without unnecessary clostridial proteins or human albumin in a lyophilized powder, and is stable at room temperature,60 like incobotulinumtoxinA.28 DaxibotulinumtoxinA includes an excipient peptide, RTP-004, consisting of the protein transduction domain sequence from the HIV-1 TAT protein at each end, separated by a peptide consisting of 35 positively charged lysine residues. The lysine residues form a core that is claimed to noncovalently bind the BoNT.21 The protein was previously believed to be useful as a carrier for a transdermal BoNT formulation (RT001)21 and is now postulated to play a role in increased duration of efficacy compared with onabotulinumtoxinA.59 The greater efficacy and duration of response with daxibotulinumtoxinA 40 U vs onabotulinumtoxinA 20 U (median, 23.6 vs 18.8 weeks) is likely due to a doubling of the dose administered rather than the excipient peptide, as no consistent significant difference in efficacy or duration of response was noted between daxibotulinumtoxinA 20 U vs onabotulinumtoxinA 20 U,59 and a similar duration of response was recently reported for onabotulinumtoxinA 40 U (median, 24.0 weeks).61 A strong dose-response has also been observed in a recently conducted randomized, double-blind study with incobotulinumtoxinA 20–100 U, with duration of treatment effect up to 9 months in some subjects and no unexpected safety findings.62 The long-term consequences of the addition of polylysine structures to BoNT are not known.


BoNT-A treatment has been available for several decades and is among the most common non-surgical cosmetic procedures worldwide, with good efficacy and safety profiles, and high levels of patient satisfaction. Because patients are seeking aesthetic treatments at increasingly younger ages, both neurotoxin protein load and protein load over time can increase the risk of diminished efficacy or treatment non-response due to neutralizing antibodies over a young individual’s lifetime.This may also impact essential treatment for therapeutic indications later in life. Clinicians should therefore consider the least immunogenic BoNT-A formulation to meet individual treatment requirements, thus minimizing potential for lack of efficacy due to neutralizing antibodies for future treatment options. IncobotulinumtoxinA currently remains the only BoNT formulation approved in commercial markets worldwide that was intentionally designed to contain only the required therapeutic BoNT component. The unique and precise purification of incobotulinumtoxinA represents innovative advances in BoNT manufacturing. The data reviewed here suggest incobotulinumtoxinA offers an advantage over other BoNT-A formulations, due to its lower potential to provoke an immune response when used clinically.


M. Kerscher has conducted clinical trials for Galderma/Q-Med, Ipsen, and Merz Pharmaceuticals GmbH (as Head of the Divi- sion of Cosmetic Sciences, University of Hamburg, Germany), and has acted as a speaker for Galderma/Q-Med and Merz Phar- maceuticals. R. Wanitphakdeedecha has no conflicts of interest to disclose. A. Trindade de Almeida is an advisor for Allergan, Galderma/Q-Med, Lupin, Mantecorp, Merz Pharmaceuticals, and Sinclair, has participated in clinical trials for Allergan, has received re-