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

Abstract

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.

Fig. 1

Proposed mechanism of enhanced DAXI binding and internalization. In vitro data suggest that RTP004, the positively-charged stabilizing excipient peptide in the DAXI formulation, increases the affinity of the daxibotulinumtoxinA for neuronal membranes, which enhances localization of DAXI at the presynaptic terminal and may, therefore, facilitate increased internalization of the botulinum toxin molecule. = DAXI/peptide complex

Fig. 2

Consistency in response to DaxibotulinumtoxinA for Injection (DAXI) treatment across Phase 2 and 3 clinical trials. Response was defined as achievement of none or mild glabellar line (GL) severity at maximum frown based on investigator assessment via the validated 4-point Investigator Global Assessment-Frown Wrinkle Severity score (ranging from none [0] to severe [3]). OLS open-label study

Fig. 3

Consistency in duration of effect (time to loss of none or mild glabellar line severity at maximum frown based on both IGA-FWS and PFWS) following DaxibotulinumtoxinA for Injection (DAXI) treatment in the Phase 3 SAKURA clinical trials. CI confidence interval, IGA-FWS Investigator Global Assessment-Frown Wrinkle Severity, PFWS Patient Frown Wrinkle Severity

Fig. 4

Median time to loss of ≥ 80% of peak treatment effect following DaxibotulinumtoxinA for Injection (DAXI) treatment in adults with moderate-to-severe cervical dystonia in the Phase 3 ASPEN-1 trial

Fig. 5

None or mild response rates for glabellar lines on 4-point investigator assessment over time. This figure presents results from multiple randomized registration studies. Such cross-study comparisons should be interpreted with caution due to potential differences in study design and subject characteristics. ¹BOTOX^® and Dysport^® data derived from US Prescribing Information Phase 3 studies in glabellar lines for each neuromodulator with data available through at least Day 120 conducted separately and presented for reference only ²Beer et al [54]. DAXI DaxibotulinumtoxinA for Injection