Clinical Immunogenicity of DaxibotulinumtoxinA for Injection in Glabellar Lines: Pooled Data from the SAKURA Phase 3 Trials

DaxibotulinumtoxinA for Injection (DAXI) is a novel botulinum toxin type A product containing daxibotulinumtoxinA with a stabilizing excipient peptide (RTP004). DAXI immunogenicity was assessed in three phase 3 glabellar line studies (two placebo-controlled, single-dose studies and an open-label repeat-dose safety study). Binding antibodies to daxibotulinumtoxinA and RTP004 were detected by validated ELISAs. Samples positive for daxibotulinumtoxinA-binding antibodies were evaluated further for titer and neutralizing antibodies by mouse protection assay. Overall, 2786 subjects received DAXI and 2823 subjects were exposed to RTP004 as DAXI (n = 2786) or placebo (n = 37). Treatment-related anti-daxibotulinumtoxinA binding antibodies were detected in 21 of 2737 evaluable subjects (0.8%). No subject developed neutralizing antibodies. Treatment-related anti-RTP004 binding antibodies were detected in 35 (1.3%) of 2772 evaluable subjects. Binding antibodies were generally transient, of low titer (<1:200), and no subject had binding antibodies to both daxibotulinumtoxinA and RTP004. All subjects with treatment-induced binding antibodies to daxibotulinumtoxinA or RTP004 achieved none or mild glabellar line severity atWeek 4 following each DAXI cycle, indicating no impact on DAXI efficacy. No subjects with binding antibodies to daxibotulinumtoxinA or RTP004 reported immune-related adverse events. This evaluation of anti-drug antibody formation with DAXI shows low rates of antibody formation to both daxibotulinumtoxinA and RTP004.