Overview of DaxibotulinumtoxinA for Injection: A Novel Formulation of Botulinum Toxin Type A

• Published in: Drugs (New York, N.Y.) N.Y.), 2021-12, Vol.81 (18), p.2091-2101
• Main Authors: Solish, Nowell, Carruthers, Jean, Kaufman, Joely, Rubio, Roman G., Gross, Todd M., Gallagher, Conor J.
• Format: Article
• Language: English
• Subjects: Amino acids; Botulinum toxin; Botulinum toxin type A; Botulinum Toxins, Type A - administration & dosage; Botulinum Toxins, Type A - adverse effects; Botulinum Toxins, Type A - therapeutic use; Clinical Trials as Topic; Delayed-Action Preparations; Dose-Response Relationship, Drug; Dystonia; Extracellular matrix; Human serum albumin; Humans; Hydrogen-Ion Concentration; Injection; Internal Medicine; Internalization; Leading; Leading Article; Medicine; Medicine & Public Health; Neuromuscular Agents - administration & dosage; Neuromuscular Agents - adverse effects; Neuromuscular Agents - therapeutic use; Neurotoxins; Peptides; Peptides - chemistry; Pharmacology/Toxicology; Pharmacotherapy; Proprietary; Proteins; Serum albumin; Skin Aging - drug effects; Spasticity; Torticollis; Torticollis - drug therapy; Toxins
• ISSN: 0012-6667; 1179-1950
• DOI: 10.1007/s40265-021-01631-w

Botulinum toxin type A (BoNTA) products are widely used for therapeutic and aesthetic indications, but there is a need for longer-lasting treatments that maintain symptom relief between injections and reduce the frequency of re-treatment. DaxibotulinumtoxinA for Injection (DAXI) is a novel BoNTA product containing highly purified 150-kDa core neurotoxin and is the first to be formulated with a proprietary stabilizing excipient peptide (RTP004) instead of human serum albumin. The positively charged RTP004 has been shown to enhance binding of the neurotoxin to neuronal surfaces, which may enhance the likelihood of neurotoxin internalization. DAXI produces robust, extended efficacy across both aesthetic and therapeutic indications. In an extensive glabellar lines clinical program, DAXI showed a high degree of efficacy, a consistent median time to loss of none or mild glabellar line severity of 24 weeks, and median time until return to baseline of up to 28 weeks. In adults with cervical dystonia, DAXI at 125 U and 250 U significantly improved Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total scores, with a median duration of efficacy of 24 and 20 weeks, respectively, which compares favorably with the 12–14 weeks’ duration reported for approved BoNTA products. Overall, DAXI was well tolerated, and the consistent extended duration of effect suggests that DAXI has the potential to improve the management of both aesthetic and therapeutic conditions. Plain Language Summary Botulinum toxin is used to block the nerve signals that cause muscles to contract. Products containing botulinum toxin are commonly given by injection to treat muscle spasms (such as cervical dystonia, a painful condition where the neck muscles contract involuntarily) and for cosmetic treatment of frown lines. However, the effects of the currently approved botulinum toxin products typically wear off about 3–4 months after injection and so the injections must be repeated regularly. A new product called DAXI (DaxibotulinumtoxinA for Injection) has been developed. In this product, the botulinum toxin is formulated with a unique protein (called RTP004) that has been designed to help deliver the botulinum toxin to the nerve cells. Research suggests that the RTP004 protein in DAXI adheres the botulinum toxin to the nerves close to the injection site, potentially making its effect last longer. To date, DAXI has been studied in over 3800 patients. The studies have shown that DAXI is effec