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Keywords:

  • botulinum toxin;
  • patent;
  • potency;
  • clinical comparability of formulations

Abstract

The majority of pharmaceutical products are patented in early phases of their discovery to preclude competition by similar products. Due to unusual circumstances (botulinum toxin is an unpatentable natural product and it is considered to be a biological weapon), technology know-how for botulinum toxin production was classified rather then available in the scientific community. Botulinum toxin type A was marketed in two pharmaceutical distinct formulations from competitor companies. Serendipity proved that the two formulations were not equipotent in terms of mouse units. From a regulatory point of view, differences in potency of distinct formulations are not a matter of concern because each formulation is licensed based on its own set of data. As far as the data in each case is sufficient to prove that a particular formulation is safe and efficacious at its defined dosage, a license for use can be granted. On the other hand, generation of data on comparability is the only way that clinicians and managers can ascertain which product (formulation, serotype) is most cost–effectiveness and to determine whether there are relevant differences in their safety profiles. The results of the systematic review of head-to-head randomised trials comparing BOTOX to Dysport suggest that the two formulations are not bioequivalent whatever the dose relationship. Data on comparative immunogenicity are not available. The indirect comparison of the results obtained in randomised clinical trials comparing BOTOX to placebo and Dysport to placebo support that intrinsic differences are present in the two products. It is concluded that comparative economic evaluations of different botulinum toxin formulations should move away from cost-minimization approaches based on the presumption of bioequivalence and move toward cost-effectiveness or cost-utility models. © 2004 Movement Disorder Society