Therapeutic botulinum toxin preparations: an update

Botulinum neurotoxin (BoNT) is approved for a wide range of therapeutic and aesthetic indications. Many other indication are treated off-label. Therapeutic BoNT preparations consist of the 150kDA two-chain neurotoxin, exerting the therapeutic effect, complexing proteins and excipients. In IncobotulinumtoxinA (INCO), the complexing proteins have been removed. More recently, two products have been approved containing the complex-free neurotoxin: DaxibotulinumtoxinA (DAXI) and RelabotulinumtoxinA (RELA). Excipients may include human serum albumin (HSA), polysorbates, NaCl, KCl, lactose, sucrose, amino acids and phosphates. HSA has been replaced by gelatine and in newer products by polysorbates. Typically, BoNT drugs are stabilised by dehydration through lyophilisation or vacuum drying. More recently, ready-to-use liquid preparations have been introduced: AbobotulinumtoxinA as Alluscience^® and RELA. Storage conditions are usually 2-8 ºC and room temperature in INCO and DAXI. DAXI contains an additional, proprietary peptide. The claim that the peptide would prolong the duration of action could not be substantiated. Most BoNT drugs use BoNT type A. BoNT type B is a niche product due to its limited number of approved indications, significant systemic autonomic adverse effects and high antigenicity due to the high amount of BoNT/B. BoNT type E is currently being developed as a drug with rapid onset and short duration of action for aesthetic indications. Recombinant and hybrid BoNT/A/B are currently also being developed.