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Surgery and Cosmetics

James M. Spencer, MD, MS

A New Formulation of Botulinum Toxin: Dysport®

James M. Spencer, MD, MS

Wednesday, March 10, 2010

AbobotulinumtoxinA, the generic name for a new formulation of botulinum toxin type A, was recently approved by the US Food and Drug Administration (FDA) for clinical use under the brand name DYSPORT®  (Ipsen Ltd.). Since 2001, Dysport® has been used for cosmetic purposes in Europe and South America, so it is not entirely a new drug. In fact, abobotulinumtoxinA (DYSPORT®) and onabotulinumtoxinA (branded as BOTOX®) consist of the same molecule - botulinum toxin type A. The botulinum toxin itself was first discovered in the 1920s and is not patentable. Furthermore, the manufacturing process is difficult, and for many years BOTOX® (Allergan Inc.) was the only available formulation in the United States. On the surface, it would appear the two are similar if not identical, with the new formulation costing approximately 10% less in the United States. However, with no new formulation we must at least consider potential differences, both positive and negative.
 

DYSPORT® versus BOTOX®

Since its introduction in the United States, early users of DYSPORT® and investigators involved in clinical trials noted some possible differences between DYSPORT® and BOTOX®. Although the toxin itself is identical, there are some significant differences in additives between these two drugs. DYSPORT® contains 300 units of toxin, 0.125 mg of albumin, and 2.5 mg of lactose. The toxin itself is freeze dried in the final step of manufacture. Whereas BOTOX® contains 100 units of toxin, 0.5 mg of albumin, and 0.9 mg of sodium chloride. In the final step of the manufacturing process, the toxin is lyophilized (vacuum dried). Is it possible that these additives and/or manufacturing differences could make identical toxins behave differently?
     
There are three suggested differences that are already finding their way into discussions on the subject. It has been anecdotally suggested that DYSPORT® by comparison with BOTOX®1,2,3:

  1. has a more rapid onset;
  2. diffuses more; and
  3. lasts longer.

 Speakers who are reporting these conclusions have tended to be those who participated in the phase III clinical trials1,2,3 of DYSPORT®. I, like other investigators, did anecdotally reach the same three conclusions. While it is certainly possible that these differences actually occur, it remains more probable that there is another reason why early users of DYSPORT® arrived at these conclusions. Firstly, in the three phase III trials conducted on DYSPORT®, while the lower range of time to onset was as fast as one day, overall the median time to onset was 3-4 days, which is the same as for BOTOX®.1,2,3 Secondly, "diffuses more" and "lasts longer" could be the result of dosing and other more important factors, such as intensity of sweating4 or muscle mass3, rather than actual biochemical differences between the two formulations. Moreover, the field effects in sweat glands around DYSPORT® injections showed efficacy and predictable "diffusion"4.

Dosage

Studies have shown that as the dose of BOTOX® increases, duration of effect increases to a point until it plateaus. It also stands to reason that as the dose increases, the spread of effect should be greater, as a large amount of toxin (in units) will be delivered and available at neuromuscular junctions allowing the blockage of a large amount of acetylcholine and consequently more positively affecting local muscles and sweat glands. Dosing of botulinum toxin is based on units of biologic activity, defined as the LD50 following intraperitoneal injection of mice. BOTOX® and DYSPORT® use different strains of mice and different protocols, and thus 1 unit of BOTOX® is not the same as 1 unit of DYSPORT®. Conversion appears to fall somewhere in the range of 2-2.5 units of DYSPORT® being equivalent to 1 unit of BOTOX®. However, given that the conversion is still uncertain, it might be that the trials of DYSPORT®were using proportionally higher doses, and thus the observed "differences" from BOTOX® are the result of higher doses, not actual differences in the formulations. Further research, time and experience will answer these questions.

Figure 1a. Before forehead treatment with DYSPORT®

 

  


Figure 1b: After forehead treatment with DYSPORT®.  

References

  1. Brandt F, Swanson N, Baumann L, Huber B. Randomized, placebo-controlled study of a new botulinum toxin type a for treatment of glabellar lines: efficacy and safety. Dermatol Surg. 2009;35:1893-1901.
  2. Rubin MG, Dover JS, Glogau RG, et al. The efficacy and safety of a new U.S. Botulinum toxin type A in the retreatment of glabellar lines following open-label treatment. J Drugs Dermatol. 2009;8:439-444.
  3. Kane MA, Brandt F, Rohrich RJ, et al. Evaluation of variable-dose treatment with a new U.S. Botulinum Toxin Type A (Dysport) for correction of moderate to severe glabellar lines: results from a phase III, randomized, double-blind, placebo-controlled study. Plast Reconstr Surg. 2009;124:1619-1629.
  4. Hexsel DM, Soirefmann M. Rodrigues TC, Prado DZ. Increasing the field effects of similar doses of Clostridium botulinum type A-toxin hemaglutinin complex in the treatment of compensatory hyperhidrosis. Arch Dermatol 2009;145:837-840.

 

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