Efficacy and safety of DaxibotulinumtoxinA for injection in adults with cervical dystonia: Pooled global analysis of ASPEN-1 and ASPEN-1-CN randomized trials

Background

DaxibotulinumtoxinA for injection (DAXI), the first long-acting botulinum toxin (BoNT) type A, is FDA approved for cervical dystonia (CD). DAXI's novel formulation, which includes a custom-engineered peptide, is designed to provide an extended duration of clinical benefit.

Objective

To evaluate the pooled efficacy and safety of DAXI for CD across two phase 3, multicenter, randomized, double-blind, placebo-controlled trials: ASPEN-1, conducted in North America and Europe, and ASPEN-1-CN, a similarly designed, smaller pivotal clinical trial, conducted in China.

Methods

Adults with moderate-to-severe CD were randomized (3:3:1) to receive DAXI 125U, DAXI 250U, or placebo. The primary endpoint was change from baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score averaged across weeks 4 and 6. A key secondary endpoint was duration, defined as time until loss of >80 % of peak effect.

Results

In all, 357 subjects were randomized and received DAXI 125U (n = 149), DAXI 250U (n = 154), or placebo (n = 54). DAXI 125U (−12.0) and DAXI 250U (−11.9) significantly improved the mean TWSTRS total score versus placebo (−4.6; P < 0.0001). Median (95 % CI) duration of effect was 24.1 (20.6–28.9) weeks for DAXI 125U and 22.0 (20.1–24.3) weeks for DAXI 250U. Rates of treatment-related dysphagia (125U: 4.7 %, 250U: 4.5 %) and muscle weakness (125U: 5.4 %, 250U: 4.5 %) were low for both active doses.

Conclusions

This pooled analysis of two phase 3 trials demonstrates that DAXI is an effective, safe, and long-acting treatment for CD. Key adverse events occurred at rates lower than prior pivotal trials of BoNTs for CD.