Injectable DaxibotulinumtoxinA in Cervical Dystonia: A Phase 2 Dose-Escalation Multicenter Study

• Type of Material: Article
• Authors: Joseph Jankovic, Baylor College; Daniel Truong, The Parkinson's and Movement Disorder Institute; Atul T. Patel, Kansas City Bone & Joint Clinic; Allison Brashear, Wake Forest Baptist Medical Center; Marian L Evatt, Emory University; Roman G. Rubio, Revance Therapeutics, Inc.; Chad K. Oh, Revance Therapeutics, Inc.; Daniel Snyder, Revance Therapeutics, Inc.; Gill Shears, Write on Target Ltd.; Cynthia Comella, Rush University Medical Center
• Language: English
• Date: 2018-05-01
• Publisher: Wiley
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/mdc3.12613
• Title of Journal or Parent Work: Movement Disorders Clinical Practice
• ISSN: 2330-1619
• Volume: 5
• Issue: 3
• Start Page: 273
• End Page: 282
• Keywords: TWSTRS; botulinum toxin; cervical dystonia; daxibotulinumtoxinA; CDIP
• Research Categories: Health Sciences, Pathology; Biology, Neuroscience

Abstract

Background: Injectable daxibotulinumtoxinA (an investigational botulinum toxin, RT002) may offer a more prolonged duration of response—and therefore less frequent dosing—than onabotulinumtoxinA. Objectives: To perform a phase 2, open-label, dose-escalation study to assess the efficacy and safety of daxibotulinumtoxinA in cervical dystonia. Methods: Subjects with moderate-to-severe isolated cervical dystonia were enrolled in sequential cohorts to receive a single open-label, intramuscular dose of injectable daxibotulinumtoxinA of up to 200 U (n = 12), 200–300 U (n = 12), or 300–450 U (n = 13; clinicaltrials.gov identifier NCT02706795). Results: Overall, 33/37 enrollees completed the trial. DaxibotulinumtoxinA was associated with mean reductions in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score of 16.8 (38%) at week 4, 21.3 (50%) at week 6, and 12.8 (30%) at week 24. The proportion of subjects who were responders (achieved ≥ 20% reduction in TWSTRS-Total score) was 94% at week 6 and 68% at week 24. The median duration of response (time until > 20% of the improvement in TWSTRS-Total score achieved at week 4 was no longer retained or re-treatment was needed) was 25.3 weeks (95% CI, 20.14–26.14 weeks). There were no serious adverse events and there was no apparent dose-related increase in the incidence of adverse events. The most common treatment-related adverse events were dysphagia (14%) and injection site erythema (8%). Conclusions: Preliminary assessments suggest that injectable daxibotulinumtoxinA at doses up to 450 U is well tolerated and may offer prolonged efficacy in the treatment of cervical dystonia. Further studies involving larger numbers of patients are now warranted.