Advertisement

Journal of Neural Transmission

, Volume 126, Issue 12, pp 1625–1629 | Cite as

Comparing lanbotulinumtoxinA (Hengli®) with onabotulinumtoxinA (Botox®) and incobotulinumtoxinA (Xeomin®) in the mouse hemidiaphragm assay

  • Lizhen Pan
  • Hans Bigalke
  • Bruno Kopp
  • Lingjing Jin
  • Dirk DresslerEmail author
Neurology and Preclinical Neurological Studies - Original Article
  • 26 Downloads

Abstract

LanbotulinumtoxinA (LAN) is manufactured and registered in China since 1994. Despite its widespread use in China and its increasing use in other Asian countries and in South America, it is not yet well known elsewhere. We wanted to compare its potency labelling using the mouse diaphragm assay (MDA), an isolated muscle model for botulinum toxin (BT) potency measurements, which is superior to clinical tests and which was recently refined as an alternative batch release assay for BT manufacturing. We also wanted to estimate LAN manufacturing quality by testing its inter-batch potency consistency. Potencies of 20, 60 and 100 MU of LAN, onabotulinumtoxinA (ONA) and incobotulinumtoxinA (INCO) were measured by the inversely related paresis time (PT) in the MDA. The PT (M ± SD) of all doses of LAN, ONA and INCO was 90.4 ± 27.0 min, 114.9 ± 46.5 min and 94.3 ± 29.9 min, respectively. Statistical analysis demonstrated indistinguishable potency labelling of LAN and INCO, but revealed a slightly lower potency of ONA compared to LAN and INCO. PT of LAN batch 1 and LAN batch 2 was 86.9 ± 21.2 min and 94.0 ± 32.8 min, respectively (no statistically significant difference), suggesting an adequate LAN manufacturing consistency. The MDA is an appropriate instrument for potency testing of BT drugs, including new ones currently under development. Our results allow comparing therapeutic effects, adverse effects and economics of LAN, ONA and INCO. They also suggest adequate manufacturing consistency of LAN.

Keywords

LanbotulinumtoxinA OnabotulinumtoxinA IncobotulinumtoxinA Hemidiaphragm assay Potency labelling Conversion factors Drug comparability Manufacturing consistency 

Notes

Funding

LP was funded by: National Natural Science Foundation of China (81500970), National Key R&D Program of China (2018YFC1314700) and Shanghai Hospital Development Center (16CR3009A). LJ was funded by: National Key R&D Program of China (2018YFC1314700), National Natural Science Foundation of China (81500970) and Shanghai Hospital Development Center (16CR3009A).

Compliance with ethical standards

Conflict of interest

DD received honoraria for consultations from Allergan, Ipsen, IAB-Interdisciplinary Working Group for Movement Disorders, Merz and Syntaxin. He is a shareholder of Allergan. He holds patents in botulinum toxin research and provides professional consulting services to pharmaceutical companies and professional investment institutions on all aspects of botulinum toxin drugs. HB is the founder and co-owner of Toxogen. LP, BK and LJ have nothing to disclose.

References

  1. Brin MF, Blitzer A (1993) Botulinum toxin: dangerous terminology errors J Roy Soc Med 86:493–494PubMedGoogle Scholar
  2. Buelbring E (1946) Observation on the isolated phrenic nerve diaphragm preparation in the rat. Br J Pharmacol 1:38–61Google Scholar
  3. Dressler D, Dirnberger G, Bhatia K, Quinn NP, Irmer A, Bigalke H (2000) Botulinum toxin antibody testing: comparison of the mouse diaphragm bioassay and the mouse lethality bioassay. Mov Disord 15(suppl 2):18–19Google Scholar
  4. Dressler D, Pan L, Bigalke H (2018) Comparing incobotulinumtoxinA (Xeomin®) and onabotulinumtoxinA (Botox®): identical potency labelling in the hemidiaphragm assay. J Neural Transm 125:1351–1354CrossRefGoogle Scholar
  5. Dressler D, Pan L, Su J, Teng F, Jin L (in press) Lantox—the Chinese Botulinum Toxin Drug. Complete English Bibliography and Formalised Literature Review. Park Rel DisordGoogle Scholar
  6. European Pharmacopoeia 6.0 (2008a) Botulinum Toxin Type A for Injection, 1327–1329Google Scholar
  7. European Pharmacopoeia 6.0 (2008b) Statistical Analysis of Biological Assays and Tests 5.3: 571–600Google Scholar
  8. Goeschel H, Wohlfahrt K, Frevert J, Dengler R, Bigalke H (1997) Botulinum A toxin: neutralizing and nonneutralizing antibodies—therapeutic consequences. Exp Neurol 147:96–102CrossRefGoogle Scholar
  9. Jiang HY, Chen S, Zhou J, Leung KK, Yu P (2014) Diffusion of two botulinum toxins type A on the forehead: double-blinded, randomized, controlled study. Dermatol Surg 40:184–192CrossRefGoogle Scholar
  10. Jiang HY, Chen S, Zhou J (2016) Diffusion comparison of two botulinum toxin A preparations in the forehead. Chin J Med Aesth Cosmetol 22:150–153 (In Chinese)Google Scholar
  11. JASP Team (2019) JASP (Version 0.9.2)Google Scholar
  12. Marion MH, Sheehy M, Sangla S, Soulayrol S (1995) Dose standardisation of botulinum toxin. J Neurol Neurosurg Psychiat 59:102–103CrossRefGoogle Scholar
  13. Marsden CD (1993) Botulinum toxin: dangerous terminology errors J Roy Soc Med 86:494Google Scholar
  14. Oliveira de Morais O, Matos Reis-Filho E, Vilela Pereira L, Martins Gomes C, Alves G (2012) Comparison of four botulinum neurotoxin type A preparations in the treatment of hyperdynamic forehead lines in men: a pilot study. J Drugs Dermatol 11:216–219PubMedGoogle Scholar
  15. Pearce LB, Borodic GE, First ER, MacCallum RD (1994) Measurement of botulinum toxin activity: evaluation of the lethality assay. Toxicol Appl Pharmacol 128:69–77CrossRefGoogle Scholar
  16. Quagliato EM, Carelli EF, Viana MA (2010) Prospective, randomised, double-blind study comparing botulinum toxins type a Botox and Prosigne for blepharospasm and hemifacial spasm treatment. Clin Neuropharmacol 33:27–31PubMedGoogle Scholar
  17. Ranoux D, Gury C, Fondarai J, Mas JL, Zuber M (2002) Respective potencies of Botox and Dysport: a double blind, randomised, crossover study in cervical dystonia. J Neurol Neurosurg Psychiatry 72:459–462PubMedPubMedCentralGoogle Scholar
  18. Tang XF, Wan XH (2000) Comparison of botox with Chinese type A botulinum. Chin Med J (Engl) 113:794–798Google Scholar
  19. Tang XF, Wan XH, Huang G, Zhang QB, Li T (1999) The treatment of focal dystonia and muscle spasms with Botox and CBTX-A. Chin J Neurol 32:135–138 (In Chinese)Google Scholar
  20. Van den Bergh P, Lison D, Dose standardisation of BTX (1996) 3rd International dystonia symposium, October 9–11, 1996, Miami, Florida. Affiliated National Dystonia Associations, Chicago, p 30Google Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  • Lizhen Pan
    • 1
    • 3
  • Hans Bigalke
    • 4
  • Bruno Kopp
    • 2
  • Lingjing Jin
    • 3
  • Dirk Dressler
    • 1
    Email author
  1. 1.Movement Disorders Section, Department of NeurologyHannover Medical SchoolHannoverGermany
  2. 2.Department of NeurologyHannover Medical SchoolHannoverGermany
  3. 3.Department of Neurology, Shanghai Tongji HospitalTongji University School of MedicineShanghaiChina
  4. 4.ToxogenHannoverGermany

Personalised recommendations