Objective: To evaluate the efficacy and safety of two doses of DaxibotulinumtoxinA for Injection (DAXI) vs placebo for treatment of cervical dystonia (CD).

Background: DAXI is a novel botulinum toxin type A product with a proprietary peptide excipient. A Phase 2 study demonstrated promising efficacy and duration of effect in CD. We report results of a large, multicenter, Phase 3 double-blind placebo-controlled trial.

Method: Adults with moderate to severe CD were randomized 1:3:3 to placebo, DAXI 125U, or DAXI 250U and followed for up to 36 weeks after a single treatment. Subjects were evaluated using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). The primary efficacy endpoint was average change from baseline in TWSTRS total score at Weeks 4 and 6. Safety was evaluated at all study visits.

Results: 301 subjects were randomized to placebo (n=46), DAXI 125U (n=125), or DAXI 250U (n=130). Demographics were similar across cohorts. Mean baseline TWSTRS total score was 43.3. Mean±SE improvement from baseline in TWSTRS total score at the primary timepoint was 4.3±1.8 for placebo, 12.7±1.3 for DAXI 125U (p<0.0001 vs placebo), and 10.9±1.2 for DAXI 250U (p=0.0006 vs placebo). There was no statistical difference in TWSTRS total score reduction between DAXI dose groups. TWSTRS Severity, Disability, and Pain subscales showed a similar magnitude of improvement from baseline: 30-33% for 125U and 25-26% for 250U vs 11-12% for placebo. Both Clinician Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC) demonstrated improvement (a little/moderately/very much better) with DAXI consistent with the primary endpoint (CGIC: 77-78% for DAXI vs 46% for placebo; PGIC: 71-73% for DAXI vs 41% for placebo). Median duration of effect was 24.0 and 20.3 weeks for DAXI 125U and DAXI 250U, as determined by time to loss of 80% peak treatment benefit.

Commonly reported treatment-related adverse events were injection site pain, headache, injection site erythema, muscular weakness, and musculoskeletal pain. Dysphagia was reported in 1.6% and 3.9% of subjects with DAXI 125U and DAXI 250U, respectively.

Conclusion: Treatment with DAXI 125U and 250U was safe and efficacious with a meaningful reduction in signs and symptoms associated with CD and a median duration of effect of 20.3-24.0 weeks.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-phase-3-trial-evaluating-the-efficacy-duration-of-effect-and-safety-of-daxibotulinumtoxina-for-injection-in-the-treatment-of-cervical-dystonia/