A Phase 3 Trial Evaluating the Efficacy, Duration of Effect, and Safety of DaxibotulinumtoxinA for Injection in the Treatment of Cervical Dystonia
Joseph Jankovic1, Cynthia Comella2, Robert A. Hauser3, Atul T. Patel4, Todd M. Gross5, Roman G. Rubio5, Domenico Vitarella5
1Parkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, 2Rush University Medical Center, 3University of South Florida, 4Kansas City Bone & Joint Clinic, 5Revance Therapeutics, Inc.
Objective:
Evaluate the efficacy and safety of DaxibotulinumtoxinA for Injection (DAXI) vs placebo for cervical dystonia (CD).
Background:
DAXI is a novel botulinumtoxinA with a proprietary peptide excipient. We report results of a multicenter, Phase 3 double-blind, placebo-controlled trial.
Design/Methods:
Adults with moderate-to-severe CD, randomized 1:3:3 (placebo, DAXI 125U, DAXI 250U), were followed for ≤36 weeks post-treatment. Primary endpoint was change from baseline (CFB) in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score averaged at Weeks 4 and 6. Safety was also evaluated.
Results:

301 subjects were randomized; placebo (n=46), DAXI 125U (n=125), DAXI 250U (n=130). Demographics were similar across cohorts. Mean±SE TWSTRS CFB at the primary timepoint was -4.3±1.8 placebo, -12.7±1.3 DAXI 125U (p<0.0001 vs placebo), and -10.9±1.2 DAXI 250U (p=0.0006 vs placebo). DAXI dose groups did not statistically differ. TWSTRS subscales showed similar improvement: 30-33%, 25-26%, and 11-12%, respectively, for DAXI 125U, 250U, and placebo. Clinician Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC) demonstrated improvement (a little to very much better) with DAXI consistent with the primary endpoint (CGIC, 77‑78% DAXI vs 46% placebo; PGIC, 71‑73% DAXI vs 41% placebo). Most DAXI-treated subjects were somewhat satisfied to very satisfied at Week 4 (DAXI 125U 69.6%; DAXI 250U 62.3%) and Week 6 (DAXI 125U 68.8%; DAXI 250U 66.2%), consistent with the primary endpoint. Median duration of effect was 24.0 and 20.3 weeks for DAXI 125U and DAXI 250U, respectively, defined as 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.

Conclusions:

Treatment with DAXI was safe and efficacious with a meaningful reduction in CD symptoms, high subject satisfaction, and median duration of effect of 20.3-24.0 weeks.